|
1
|
Kitsugi K, Kawata K, Noritake H, Chida T, Ohta K, Ito J, Takatori S, Yamashita M, Hanaoka T, Umemura M, Matsumoto M, Morita Y, Takeda M, Furuhashi S, Kitajima R, Muraki R, Ida S, Matsumoto A, Suda T. Prognostic value of neutrophil to lymphocyte ratio in patients with advanced pancreatic ductal adenocarcinoma treated with systemic chemotherapy. Ann Med 2024; 56:2398725. [PMID: 39221763 PMCID: PMC11370686 DOI: 10.1080/07853890.2024.2398725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2024] [Revised: 08/10/2024] [Accepted: 08/12/2024] [Indexed: 09/04/2024] Open
Abstract
OBJECTIVES Although systemic chemotherapy for pancreatic ductal adenocarcinoma (PDAC) has made progress, ensuring long-term survival remains difficult. There are several reports on the usefulness of neutrophil-to-lymphocyte ratio (NLR) in predicting the prognosis of PDAC, but few reports in systemic chemotherapy. We hereby investigated the usefulness of NLR in systemic chemotherapy for PDAC. MATERIALS AND METHODS A retrospective study was conducted on patients with advanced PDAC treated with first-line systemic chemotherapy. Cox regression hazards models were performed to analyze the association between baseline patient characteristics and the initial treatment response, and overall survival (OS). RESULTS A total of 60 patients with PDAC were enrolled. At baseline, there were significant differences in NLR and carbohydrate antigen 19-9 (CA19-9), as well as the selection rate of combination chemotherapy, between patients with partial response or stable disease and those with progressive disease. Univariate and multivariate analysis showed that NLR < 3.10, combination chemotherapy, and CA19-9 < 1011 U/mL were significant and independent predictive factors of the initial treatment response. Meanwhile, NLR < 3.10 and combination chemotherapy were independently associated with longer OS. Moreover, OS was significantly prolonged in patients with NLR < 3.10, regardless of whether combination chemotherapy or monotherapy. Patients with NLR < 3.10 at baseline had a significantly higher conversion rate to third-line chemotherapy and a longer duration of total chemotherapy. CONCLUSIONS This study suggests that NLR may be a useful marker for predicting the initial treatment response to first-line chemotherapy and the prognosis for patients with advanced PDAC.
Collapse
Affiliation(s)
- Kensuke Kitsugi
- Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Kazuhito Kawata
- Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Hidenao Noritake
- Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Takeshi Chida
- Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Kazuyoshi Ohta
- Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Jun Ito
- Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Shingo Takatori
- Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Maho Yamashita
- Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Tomohiko Hanaoka
- Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Masahiro Umemura
- Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Moe Matsumoto
- Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Yoshifumi Morita
- Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Makoto Takeda
- Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Satoru Furuhashi
- Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Ryo Kitajima
- Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Ryuta Muraki
- Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Shinya Ida
- Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Akio Matsumoto
- Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Takafumi Suda
- Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu, Japan
| |
Collapse
|
|
2
|
Araki T, Kawahira M, Shimokawa M, Otsuka T, Hayashi K, Sonoda Y, Honda T, Nakao K, Shibuki T, Nakazawa J, Arima S, Fukahori M, Miwa K, Koga F, Ueda Y, Kubotsu Y, Makiyama A, Shimokawa H, Takeshita S, Nishikawa K, Komori A, Otsu S, Hosokawa A, Sakai T, Oda H, Arita S, Taguchi H, Tsuneyoshi K, Kawaguchi Y, Fujita T, Sakae T, Nio K, Ide Y, Ureshino N, Shirakawa T, Mizuta T, Mitsugi K. Real-World Analysis of the Correlation between Overall Survival and Progression-Free Survival in Advanced Pancreatic Cancer: Results of NAPOLEON-1 and 2 Studies. Oncology 2024:1-11. [PMID: 39427640 DOI: 10.1159/000542137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Accepted: 10/11/2024] [Indexed: 10/22/2024]
Abstract
INTRODUCTION Fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) improve overall survival (OS) and progression-free survival (PFS) in patients with pancreatic cancer, compared with gemcitabine (GEM). However, whether PFS is a surrogate marker of OS in pancreatic cancer chemotherapy focusing on FOLFIRINOX or GEM plus nab-paclitaxel remains unknown. We aimed to verify whether PFS can be a surrogate marker of OS in prognosis prediction. METHODS This was an integrated analysis of the NAPOLEON study and retrospective cohort of the NAPOLEON-2 study - a multicenter observational study conducted in Japan, using real-world data. The primary and secondary endpoints were OS and PFS, respectively. The correlation between OS and PFS in first- and second-line treatments was assessed using Method of Moments estimation. An analysis was performed in patients with confirmed OS at the end of follow-up. The NAPOLEON-2 cohort included only patients who received 5-fluorouracil, leucovorin, and nanoliposomal irinotecan (NFF) as second-line treatment. RESULTS Among 479 patients, the correlation between PFS and OS from first- and second-line chemotherapies was calculated in 310 and 225 patients, respectively. The R-squared values for the correlation between PFS and OS from first- and second-line chemotherapies were 0.74 and 0.76, respectively. There was no statistically significant difference in first-line treatment between the FOLFIRINOX and GEM plus nab-paclitaxel groups (p = 0.92). Therefore, the FOLFIRINOX group may not have shown a stronger correlation than the NFF group. CONCLUSION PFS can be a surrogate marker of OS in first- and second-line therapies. Appropriate prognostic estimation might contribute to proper treatment selection.
Collapse
Affiliation(s)
- Tomonori Araki
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan,
| | - Machiko Kawahira
- Department of Gastroenterology, Kagoshima Kouseiren Hospital, Kagoshima, Japan
| | - Mototsugu Shimokawa
- Clinical Research Institute, National Kyushu Cancer Center, Fukuoka, Japan
- Department of Biostatistics, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| | - Taiga Otsuka
- Department of Medical Oncology, Saga-Ken Medical Center Koseikan, Saga, Japan
- Department of Internal Medicine, Minato Medical Clinic, Fukuoka, Japan
| | - Kohei Hayashi
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
| | - Yuki Sonoda
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
| | - Takuya Honda
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
| | - Kazuhiko Nakao
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
| | - Taro Shibuki
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Chiba, Japan
| | - Junichi Nakazawa
- Department of Medical Oncology, Kagoshima City Hospital, Kagoshima, Japan
| | - Shiho Arima
- Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Masaru Fukahori
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan
| | - Keisuke Miwa
- Multidisciplinary Treatment Cancer Center, Kurume University Hospital, Fukuoka, Japan
| | - Futa Koga
- Department of Hepatobiliary and Pancreatology, Saga Medical Center Koseikan, Saga, Japan
| | - Yujiro Ueda
- Department of Hematology and Oncology, Japanese Red Cross Kumamoto Hospital, Kumamoto, Japan
| | - Yoshihito Kubotsu
- Department of Internal Medicine, Karatsu Red Cross Hospital, Saga, Japan
| | - Akitaka Makiyama
- Department of Hematology Oncology, Japan Community Healthcare Organization Kyushu Hospital, Fukuoka, Japan
| | - Hozumi Shimokawa
- Department of Hematology Oncology, Japan Community Healthcare Organization Kyushu Hospital, Fukuoka, Japan
| | - Shigeyuki Takeshita
- Department of Gastroenterology, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan
| | - Kazuo Nishikawa
- Department of Medical Oncology and Hematology, Oita University Faculty of Medicine, Oita, Japan
| | - Azusa Komori
- Department of Medical Oncology and Hematology, Oita University Faculty of Medicine, Oita, Japan
| | - Satoshi Otsu
- Department of Medical Oncology and Hematology, Oita University Faculty of Medicine, Oita, Japan
| | - Ayumu Hosokawa
- Department of Clinical Oncology, University of Miyazaki Hospital, Miyazaki, Japan
| | - Tatsunori Sakai
- Department of Medical Oncology, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan
| | - Hisanobu Oda
- Division of Integrative Medical Oncology, Saiseikai Kumamoto Hospital, Kumamoto, Japan
| | - Shuji Arita
- Department of Chemotherapy, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan
| | - Hiroki Taguchi
- Department of Gastroenterology, Saiseikai Sendai Hospital, Kagoshima, Japan
| | - Kengo Tsuneyoshi
- Department of Gastroenterology, Izumi General Medical Center, Kagoshima, Japan
| | - Yasunori Kawaguchi
- Department of Gastroenterology, Asakura Medical Association Hospital, Fukuoka, Japan
| | - Toshihiro Fujita
- Department of Gastroenterology, Saiseikai Sendai Hospital, Kagoshima, Japan
| | - Takahiro Sakae
- Department of Gastroenterology, Saiseikai Sendai Hospital, Kagoshima, Japan
| | - Kenta Nio
- Department of Medical Oncology, Sasebo Kyosai Hospital, Nagasaki, Japan
| | - Yasushi Ide
- Department of Internal Medicine, Karatsu Red Cross Hospital, Saga, Japan
| | - Norio Ureshino
- Department of Medical Oncology, Saga-Ken Medical Center Koseikan, Saga, Japan
| | - Tsuyoshi Shirakawa
- Clinical Hematology Oncology Treatment Study Group, Fukuoka, Japan
- Eikoh Hospital, Fukuoka, Japan
| | - Toshihiko Mizuta
- Department of Internal Medicine, Imari Arita Kyoritsu Hospital, Saga, Japan
| | - Kenji Mitsugi
- Department of Medical Oncology, Sasebo Kyosai Hospital, Nagasaki, Japan
- Department of Medical Oncology, Hamanomachi Hospital, Fukuoka, Japan
| |
Collapse
|
|
3
|
Taşçı EŞ, Oyan B, Sönmez Ö, Mutlu AU, Atcı MM, Sakin A, Öner İ, Çınkır HY, Eryılmaz MK, Çağlayan D, Balçık OY, Paksoy N, Karabulut S, Salim DK, Bilir C, Özen M, Özçelik M, Arıcan A, Akagündüz B, İnal A, Aydın D, Özer L, Gülmez A, Turhal NS, Esen SA, Algın E, Akbaş S, İriağaç Y, Şakalar T, Ünal Ç, Er Ö, Seçmeler Ş, Bozkurt M. Comparing the efficacy of regorafenib and 5-fluorouracil-based rechallenge chemotherapy in the third-line treatment of metastatic colorectal cancer. BMC Cancer 2024; 24:16. [PMID: 38166764 PMCID: PMC10763265 DOI: 10.1186/s12885-023-11783-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 12/21/2023] [Indexed: 01/05/2024] Open
Abstract
BACKGROUND The optimal treatment for metastatic colorectal cancer (mCRC) after the second line is still controversial. Regorafenib has been the standard of care in this setting as it improved overall survival (OS) compared to placebo. In real-world practice chemotherapy rechallenge is also a preferred option even though supporting evidence is not enough. We aim to compare the efficacy of regorafenib and 5-fluorouracil-based (5-FU) rechallenge treatment in the third line setting of mCRC. METHODS In this retrospective multi-institutional trial, mCRC patients from 21 oncology centers who progressed after 2 lines of chemotherapy were analyzed. Patients who were treated with regorafenib or rechallenge therapy in the third-line setting were eligible. Rechallenge chemotherapy was identified as the re-use of the 5-FU based regimen which was administered in one of the previous treatment lines. OS, disease control rate (DCR), progression free survival (PFS) and toxicity were analyzed. RESULTS Three hundred ninety-four mCRC patients were included in the study. 128 (32.5%) were in the rechallenge, and 266 (67.5%) were in the regorafenib group. Median PFS was 5.82 months in rechallenge and 4 months in regorafenib arms (hazard ratio:1.45,95% CI, p = 0.167). DCR was higher in the rechallenge group than regorafenib (77% vs 49.5%, respectively, p = < 0.001). Median OS after the third-line treatment was 11.99 (95% CI, 9.49-14.49) and 8.08 months (95% CI, 6.88-9.29) for rechallenge and regorafenib groups, respectively (hazard ratio:1.51, 95% CI, p < 0.001). More adverse effects and discontinuation were seen with regorafenib treatment. CONCLUSION Our study revealed that higher disease control and OS rates were achieved with rechallenge treatment compared to regorafenib, especially in patients who achieved disease control in one of the first two lines of therapy.
Collapse
Affiliation(s)
- Elif Şenocak Taşçı
- Department of Medical Oncology, Saglık Bilimleri University, Kanuni Sultan Süleyman Research and Training Hospital, Istanbul, Turkey.
| | - Başak Oyan
- Department of Medicine, Acıbadem MAA University, Istanbul, Turkey
| | - Özlem Sönmez
- Department of Medicine, Acıbadem MAA University, Istanbul, Turkey
| | - Arda Ulaş Mutlu
- Department of Medicine, Acıbadem MAA University, Istanbul, Turkey
| | - Muhammed Mustafa Atcı
- Department of Medical Oncology, Haseki Education and Research Hospital, Istanbul, Turkey
| | - Abdullah Sakin
- Department of Medical Oncology, Medipol Bahçelievler Hospital, Istanbul, Turkey
| | - İrem Öner
- Department of Medical Oncology, Konya City Hospital, Konya, Turkey
| | - Havva Yeşil Çınkır
- Department of Medical Oncology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
| | - Melek Karakurt Eryılmaz
- Meram Faculty of Medicine, Department of Medical Oncology, Necmettin Erbakan University, Konya, Turkey
| | - Dilek Çağlayan
- Meram Faculty of Medicine, Department of Medical Oncology, Necmettin Erbakan University, Konya, Turkey
| | - Onur Yazdan Balçık
- Department of Medical Oncology, Mardin Education and Research Hospital, Mardin, Turkey
| | - Nail Paksoy
- Department of Medical Oncology, Tekirdağ Dr. İsmail Fehmi Cumalıoğlu City Hospital, Tekirdağ, Turkey
| | - Senem Karabulut
- Department of Medical Oncology, Şişli Kolan Hospital, Istanbul, Turkey
| | - Derya Kıvrak Salim
- Department of Medical Oncology, Antalya Education and Research Hospital, Antalya, Turkey
| | - Cemil Bilir
- Department of Medical Oncology, Medical Park Hospital, Istanbul, Turkey
| | - Miraç Özen
- Department of Medical Oncology, Sakarya University Research and Education Hospital, Sakarya, Turkey
| | - Melike Özçelik
- Department of Medical Oncology, University of Health Sciences Umraniye Education and Research Hospital, Istanbul, Turkey
| | - Ali Arıcan
- Department of Medicine, Acıbadem MAA University, Istanbul, Turkey
| | - Baran Akagündüz
- Department of Medical Oncology, Binali Yıldırım University, Erzincan, Turkey
| | - Ali İnal
- Department of Medical Oncology, Mersin City Hospital, Mersin, Turkey
| | - Dinçer Aydın
- Department of Medical Oncology, Derince Education and Research Hospital, Kocaeli, Turkey
| | - Leyla Özer
- Department of Medicine, Acıbadem MAA University, Istanbul, Turkey
| | - Ahmet Gülmez
- Department of Medical Oncology, Adana City Hospital, Adana, Turkey
| | | | - Selin Aktürk Esen
- Department of Medical Oncology, Ankara City Hospital, Ankara, Turkey
| | - Efnan Algın
- Department of Medical Oncology, Ankara City Hospital, Ankara, Turkey
| | - Sinem Akbaş
- Department of Medical Oncology, Koç University Hospital, Istanbul, Turkey
| | - Yakup İriağaç
- Department of Medical Oncology, Namık Kemal University, Tekirdağ, Turkey
| | - Teoman Şakalar
- Department of Medical Oncology, Necip Fazıl City Hospital, Kahramanmaraş, Turkey
| | - Çağlar Ünal
- Department of Medical Oncology, Bilim University, Istanbul, Turkey
| | - Özlem Er
- Department of Medicine, Acıbadem MAA University, Istanbul, Turkey
| | - Şaban Seçmeler
- Department of Medical Oncology, Medical Park Bahçelievler Hospital, Istanbul, Turkey
| | - Mustafa Bozkurt
- Department of Medicine, Acıbadem MAA University, Istanbul, Turkey
| |
Collapse
|
|
4
|
Kato T, Kudo T, Kagawa Y, Murata K, Ota H, Noura S, Hasegawa J, Tamagawa H, Ohta K, Ikenaga M, Miyazaki S, Komori T, Uemura M, Nishimura J, Hata T, Matsuda C, Satoh T, Mizushima T, Ohno Y, Yamamoto H, Doki Y, Eguchi H. Phase II dose titration study of regorafenib in progressive unresectable metastatic colorectal cancer. Sci Rep 2023; 13:2331. [PMID: 36759648 PMCID: PMC9911606 DOI: 10.1038/s41598-022-24057-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Accepted: 11/09/2022] [Indexed: 02/11/2023] Open
Abstract
Regorafenib has shown significant survival benefit as a salvage therapy for colorectal cancer; however, its starting dose has been controversial in recent studies. Therefore, we conducted a prospective study on the efficacy and safety of the dose reduction of regorafenib to 120 mg. Patients received 120 mg regorafenib once per day for 3 weeks, followed by a 1-week off-treatment period. The primary endpoint was the investigator-assessed disease control rate (DCR). Sixty patients were registered, and the DCR was 38.3% with a median progression-free survival of 2.5 months (95% confidence interval [CI] 1.9-3.7) and median overall survival of 10.0 months (95% CI 6.9-15.2). Common grade 3-4 adverse events were hand-foot skin reaction and hypertension (20.0% each). The results of administration of 120 mg regorafenib as the starting dose are consistent with reports from prior phase III trials, which used starting doses of 160 mg. This lower initiating dose of regorafenib may be beneficial to certain patient populations. This clinical trial was registered in the UMIN Clinical Trials Registry (UMIN-CTR number UMIN000018968, registration date: 10/09/2015).
Collapse
Affiliation(s)
- Takeshi Kato
- Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan
| | - Toshihiro Kudo
- Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Suita, Japan.
| | - Yoshinori Kagawa
- Department of Colorectal Surgery, Kansai Rosai Hospital, Amagasaki, Japan
| | - Kohei Murata
- Department of Colorectal Surgery, Kansai Rosai Hospital, Amagasaki, Japan
| | - Hirofumi Ota
- Department of Digestive Surgery, Ikeda City Hospital, Ikeda, Japan
| | - Shingo Noura
- Department of Surgery, Osaka Rosai Hospital, Sakai, Japan
| | | | | | - Katsuya Ohta
- Department of Gastroenterological Surgery, Higashiosaka City Medical Center, Higashiosaka, Japan
| | - Masakazu Ikenaga
- Department of Gastroenterological Surgery, Higashiosaka City Medical Center, Higashiosaka, Japan
| | - Susumu Miyazaki
- Department of Surgery, Osaka General Medical Center, Osaka, Japan
| | - Takamichi Komori
- Department of Surgery, Osaka General Medical Center, Osaka, Japan
| | - Mamoru Uemura
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan
| | - Junichi Nishimura
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan
| | - Taishi Hata
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan
| | - Chu Matsuda
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan
| | - Taroh Satoh
- Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Suita, Japan
| | - Tsunekazu Mizushima
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan
| | - Yuko Ohno
- Department of Mathematical Health Science, Graduate School of Medicine, Osaka University, Suita, Japan
| | - Hirofumi Yamamoto
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan
| |
Collapse
|
|
5
|
Rosati G, Montrone M, Pacilio C, Colombo A, Cicero G, Paragliola F, Vaia A, Annunziata L, Bilancia D. An Update on the Role of Anti-EGFR in the Treatment of Older Patients with Metastatic Colorectal Cancer. J Clin Med 2022; 11:jcm11237108. [PMID: 36498683 PMCID: PMC9739901 DOI: 10.3390/jcm11237108] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2022] [Revised: 11/10/2022] [Accepted: 11/27/2022] [Indexed: 12/02/2022] Open
Abstract
Although colorectal cancer is increasingly being diagnosed in older patients, their number is largely underrepresented in phase II or III clinical trials. Consequently, guidelines and the SIOG recommendations are not sufficiently clear regarding the treatment of these patients, particularly when chemotherapy is combined with monoclonal antibodies (bevacizumab, cetuximab, and panitumumab). Targeted therapy based on the use of anti-epidermal growth factor receptors (EGFRs) is conditioned by the potential for increased toxicity, making it more difficult to treat an older, rat sarcoma virus (RAS) and B rapidly accelerated fibrosarcoma (BRAF) wild-type patient. In light of a more detailed characterization of the older population, modernly differentiable between fit, vulnerable, or frail patients on the basis of the comprehensive geriatric assessment, and of the analysis of more recent studies, this review fully collects data from the literature, differentiating the results on functional status patients.
Collapse
Affiliation(s)
- Gerardo Rosati
- Medical Oncology Unit, “San Carlo” Hospital, 85100 Potenza, Italy
- Correspondence: ; Tel.: +39-0971-612273
| | - Michele Montrone
- Medical Thoracic Oncology Unit, IRCCS Istituto Tumori “Giovanni Paolo II”, 70124 Bari, Italy
| | - Carmen Pacilio
- Medical Breast Cancer Department, IRCCS Istituto Tumori “G. Pascale”, 80131 Napoli, Italy
| | - Alfredo Colombo
- Medical Oncology Unit, CDC Macchiarella, 90138 Palermo, Italy
| | - Giuseppe Cicero
- Medical Oncology, Università degli Studi di Palermo, 90133 Palermo, Italy
| | | | - Angelo Vaia
- Medical Oncology Unit, “San Carlo” Hospital, 85100 Potenza, Italy
| | - Luigi Annunziata
- Medical Oncology Unit, “San Carlo” Hospital, 85100 Potenza, Italy
| | | |
Collapse
|
|
6
|
Franko J, Yin J, Adams RA, Zalcberg J, Fiskum J, Van Cutsem E, Goldberg RM, Hurwitz H, Bokemeyer C, Kabbinavar F, Curtis A, Meyers J, Chibaudel B, Yoshino T, de Gramont A, Shi Q. Trajectories of body weight change and survival among patients with mCRC treated with systemic therapy: Pooled analysis from the ARCAD database. Eur J Cancer 2022; 174:142-152. [PMID: 35994794 DOI: 10.1016/j.ejca.2022.07.021] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Revised: 07/14/2022] [Accepted: 07/17/2022] [Indexed: 11/03/2022]
Abstract
BACKGROUND Higher body mass index is associated with a higher incidence of colorectal cancer (CRC) but also with improved survival in metastatic CRC (mCRC). Whether weight change after mCRC diagnosis is associated with survival remains largely unknown. METHODS We analysed individual patient data for previously untreated patients enrolled in five phase 3 randomised trials conducted between 1998 and 2006. Weight measurements were prospectively collected at baseline and up to 59.4 months after diagnosis. We used stratified multivariable Cox models to assess the prognostic associations of weight loss with overall and progression-free survival, adjusting for other factors. The primary end-point was a difference in overall survival (OS) between populations with weight loss and stable or increasing weight. FINDINGS Data were available for 3504 patients. The median weight change at 3 months was -0.54% (IQR -3.9 … +1.5%). We identified a linear trend of increasing risk of death associated with progressive weight loss. Unstratified median OS was 20.5, 18.0, and 11.9 months (p < 0.001) for stable weight or gain, <5% weight loss, and ≥5% weight loss at 3 months, respectively. Weight loss was associated with a higher risk of death (<5% loss: aHR 1.18 [1.06-1.30], p < 0.002; ≥5% loss: aHR 1.87 [1.67-2.1], p < 0.001) as compared to stable or increasing weight at 3 months post-baseline (reference), while adjusting for age, sex, performance, and a number of metastatic sites. INTERPRETATION Patients losing weight during systemic therapy for metastatic colorectal cancer have significantly shorter OS. The degree of weight loss is proportional to the observed increased risk of death and remains evident among underweight, normal weight, and obese individuals. On-treatment weight change could be used as an intermediate end-point. FUNDING The creation and management of the database containing the individual patient data from the original randomised trials is supported by the Aide et Recherche en Cancérologie Digestive Foundation.
Collapse
Affiliation(s)
- Jan Franko
- MercyOne Medical Center, Des Moines, IA, USA.
| | - Jun Yin
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA
| | | | - John Zalcberg
- School of Public Health and Preventative Medicine, Monash University, Melbourne, Australia
| | - Jack Fiskum
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA
| | - Eric Van Cutsem
- Digestive Oncology, University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium
| | | | | | - Carsten Bokemeyer
- Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | | | | | - Jeffery Meyers
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA
| | - Benoist Chibaudel
- Department of Medical Oncology, Hôpital Franco-Britannique - Fondation Cognacq-Jay, Levallois-Perret, France
| | - Takayuki Yoshino
- Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Japan
| | - Aimery de Gramont
- Department of Medical Oncology, Hôpital Franco-Britannique - Fondation Cognacq-Jay, Levallois-Perret, France
| | - Qian Shi
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA
| |
Collapse
|
|
7
|
Papamichael D, Lopes GS, Olswold CL, Douillard JY, Adams RA, Maughan TS, Van Cutsem E, Venook AP, Lenz HJ, Heinemann V, Kaplan R, Bokemeyer C, Chibaudel B, Grothey A, Yoshino T, Zalcberg J, De Gramont A, Shi Q. Efficacy of anti-epidermal growth factor receptor agents in patients with RAS wild-type metastatic colorectal cancer ≥ 70 years. Eur J Cancer 2022; 163:1-15. [PMID: 35033994 DOI: 10.1016/j.ejca.2021.12.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 11/29/2021] [Accepted: 12/01/2021] [Indexed: 12/24/2022]
Abstract
PURPOSE Colorectal cancer (CRC) affects many older adults. We investigated the efficacy and safety of adding anti-epidermal growth factor receptor (EGFR) agents to doublet chemotherapy (DC) in older patients. METHODS Patients with RAS wild-type (WT) metastatic CRC (mCRC) receiving first-line DC + anti-EGFR (n = 1191) or DC alone (n = 729) from seven trials in the Aide de Recherche en Cancerologie Digestive database were included. The prognostic and predictive effects of age were investigated. Progression-free and overall survival (OS) were evaluated between age groups (≥70 vs <70) for DC + anti-EGFR. In addition, outcomes were compared between DC+/-anti-EGFR within age groups in three trials with a DC alone arm. Subsequently, the same analysis was conducted for left-sided tumours. Adverse events grade ≥3 (G3+) were compared between age groups. RESULTS Older (vs younger) patients receiving DC + anti-EGFR had similar progression-free survival (PFS) (8.7 vs 10.3 months; hazard ratio (HR) = 1.20 [0.96-1.49];p = 0.107) but inferior OS (21.3 vs 26.3; HR = 1.36 [1.08-1.72];p = 0.011). DC + anti-EGFR (vs DC alone) improved OS (23.9 vs 20.3; HR = 0.82 [0.70-0.95];p = 0.008) and PFS (11.2 vs 8.9; HR = 0.70 [0.60-0.82];p < 0.001) in younger but not older patients: OS (24.7 vs 17.6; HR [95% confidence interval {CI}] = 0.77 [0.58-1.04];p = 0.092) and PFS (9.1 vs 8.7; HR [95% CI] = 0.85[0.63-1.15];p = 0.287). In left-sided 'only' tumours, the following outcomes for older (vs younger) patients were observed. For DC + anti-EGFR, PFS 9 versus 11.2 months; HR1.10 (95% CI 0.83-1.46); p = 0.52, OS 25.6 vs 30.3 HR 1.32 (95% CI 0.97-1.79), p = 0.086. For DC + anti-EGFR (vs DC alone), PFS and OS for younger patients were 11.9 vs 9.2 months HR 0.60 (95% CI 0.47-0.78) p < 0.001 and 24.1 versus 23.3 months HR 0.84 (95% CI 0.67-1.04), respectively. For older patients, PFS and OS were 13.1 versus 8.5 months, HR 0.51 (95% CI, 0.28-0.93), P = 0.027 and 26.3 versus 16.5 months HR 0.49 (95% CI, 0.28-0.85), respectively. There was no significant difference in toxicity among different age groups. CONCLUSIONS Older (vs younger) patients with mCRC RAS WT patients had comparable toxicity and efficacy with the addition of anti-EGFR agents to chemotherapy.
Collapse
Affiliation(s)
| | - Guilherme S Lopes
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA
| | - Curt L Olswold
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA
| | - Jean-Yves Douillard
- University of Nantes, And Integrated Centers of Oncology ICO René Gauducheau Cancer, Nantes, France
| | | | | | - Eric Van Cutsem
- Digestive Oncology, University Hospitals Gasthuisberg Leuven and University of Leuven, Leuven, Belgium
| | - Alan P Venook
- Helen Diller Family Comprehensive Cancer Center, USA
| | - Heinz-Josef Lenz
- Department of Gastrointestinal Onocology, Keck School of Medicine at USC, Los Angeles, CA, USA
| | - Volker Heinemann
- Department of Medicine III, University Hospital, Ludwig Maximilian University, Munich, Germany
| | - Richard Kaplan
- Medical Research Council Clinical Trials Unit, University College London, London, UK
| | - Carsten Bokemeyer
- Department of Oncology, Haematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | | | - Axel Grothey
- West Cancer Center and Research Institute, OneOncology, Germantown, TN, USA
| | - Takayuki Yoshino
- Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Japan
| | - John Zalcberg
- School of Public Health and Preventative Medicine, Monash University, Melbourne, Australia
| | | | - Qian Shi
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA
| |
Collapse
|
|
8
|
Temraz S, Nasr F, Kattan J, Abigerges D, Moukadem W, Farhat F, Maatouk L, Chahine G, Shamseddine A. A Non-Interventional Multicenter Study of First-Line Bevacizumab in Combination with Chemotherapy in Patients with Metastatic Colorectal Cancer in Lebanon. Biologics 2022; 16:7-15. [PMID: 35221671 PMCID: PMC8881008 DOI: 10.2147/btt.s340525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 12/23/2021] [Indexed: 11/30/2022]
Abstract
Purpose When combined with chemotherapy, bevacizumab improves progression-free survival (PFS) in metastatic colorectal cancer (mCRC). This observational trial was designed to assess the safety and efficacy of bevacizumab plus first-line chemotherapy in a real-world setting in Lebanon. Patients and Methods A non-interventionaL multicenter study of first-LIne AVastin® (bevacizumab) in combination with chEmotherapy in patients with metastatic colorectal cancer (LLIVE) is a multicenter, prospective, Lebanon-based, observational study that enrolled mCRC patients who received first-line bevacizumab plus chemotherapy combination. The primary end point of the study was PFS. Secondary endpoints comprised the overall response rate (ORR) and the safety and tolerability of bevacizumab. Results A total of 196 patients were enrolled between July 2010 and August 2013. The median duration of follow-up was 11 months. Median duration of bevacizumab treatment was 4 months with FOLFOX being the chiefly chemotherapy regimen used in the first-line setting (26%). Median PFS was 8.22 months (95% confidence interval (CI): 7.005–9.443). The ORR was 50.3% (complete response 7.5%, partial response 42.8%). The most common adverse event encountered was hypertension (28%) followed by epistaxis (4.8%), diarrhea (4%), anemia (4%) and headache (4%). Grade 3/4 adverse events occurred in 15.2% of patients. Conclusion The trial further substantiated the efficacy and safety of bevacizumab and chemotherapy in the first-line treatment of mCRC patients in Lebanon.
Collapse
Affiliation(s)
- Sally Temraz
- Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Fadi Nasr
- Department of Hematology and Oncology, Mount Lebanon Hospital, Beirut, Lebanon
| | - Joseph Kattan
- Department of Hematology and Oncology, Saint- Joseph University, Beirut, Lebanon
| | - Dany Abigerges
- Department of Hematology and Oncology, Middle East Institute of Health, Bsalim, Lebanon
| | - Walid Moukadem
- Department of Hematology and Oncology, Haykal Hospital, Tripoli, Lebanon
| | - Fadi Farhat
- Department of Hematology and Oncology, Hammoud Hospital University Medical Center, Saida, Lebanon
| | | | - Georges Chahine
- Department of Hematology and Oncology, Hôtel-Dieu de France University Hospital, Beirut, Lebanon
| | - Ali Shamseddine
- Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
- Correspondence: Ali Shamseddine, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon, Tel +961 1 374374, Fax +961 1 370814, Email
| |
Collapse
|
|
9
|
Sharma V, Sharma A, Raina V, Dabkara D, Mohanti BK, Shukla NK, Pathy S, Thulkar S, Deo SVS, Kumar S, Sahoo RK. Metastatic colo-rectal cancer: real life experience from an Indian tertiary care center. BMC Cancer 2021; 21:630. [PMID: 34049505 PMCID: PMC8164292 DOI: 10.1186/s12885-021-08398-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Accepted: 05/06/2021] [Indexed: 11/10/2022] Open
Abstract
Background No data exist for the long-term outcome of metastatic colorectal cancer (mCRC) from the Southern part of Asia. The primary objective of the study is to evaluate the survival outcome of mCRC from an Indian tertiary care center. The study also aims to highlight the treatment pattern practiced and the unique clinico-pathologic characteristics. Methods This is a single-center retrospective observational study done at a large referral tertiary care center in North India. All patients with synchronous or metachronous mCRC who received at least one dose of chemotherapy for metastatic disease, registered between 2003 to 2017 were included. Primary outcome measures were overall survival and progression-free survival and prognostic factors of overall survival. Descriptive analysis was done for the clinicopathological characteristics and treatment patterns. Kaplan Meier method for overall survival and progression-free survival. Cox regression analysis was performed for the determination of the prognostic factors for overall survival. Result Out of 377 eligible patients, 256 patients (68%) had de novo metastatic disease and the remaining 121 (32%) progressed to metastatic disease after initial treatment. The cohort was young (median age, 46 years) with the most common primary site being the rectum. A higher proportion of signet (9%) and mucinous histology (24%). The three common sites of metastasis were the liver, peritoneum, and lung. In the first line, most patients received oxaliplatin-based chemotherapy (70%). Only 12.5% of patients received biologicals in the first-line setting. The median follow-up and median overall survival of study cohort were 17 months and 18.5 months. The factors associated with poor outcome for overall survival on multivariate analysis were ECOG performance status of > 1, high CEA, low albumin, and the number of lines of chemotherapy received (< 2). Conclusion The outcome of mCRC is inferior to the published literature. We found a relatively higher proportion of patients with the following characteristics; younger, rectum as primary tumor location, the signet, and mucinous histology, higher incidence of peritoneum involvement. The routine use of targeted therapies is limited. Government schemes (inclusion of targeted therapies in the Ayushman scheme), NGO assistance, and availability of generic low-cost targeted drugs may increase the availability.
Collapse
Affiliation(s)
- Vinod Sharma
- Department of Medical Oncology, Dr BRA IRCH, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - Atul Sharma
- Department of Medical Oncology, Dr BRA IRCH, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
| | - Vinod Raina
- Department of Medical Oncology, Dr BRA IRCH, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - Deepak Dabkara
- Department of Medical Oncology, Tata Memorial Center, Kolkata, India
| | - Bidhu Kalyan Mohanti
- Department of Radiotherapy, Dr BRA IRCH, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - N K Shukla
- Department of Surgical Oncology, Dr BRA IRCH, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - Sushmita Pathy
- Department of Radiotherapy, Dr BRA IRCH, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - Sanjay Thulkar
- Department of Radiodiagnosis, Dr BRA IRCH, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - S V S Deo
- Department of Surgical Oncology, Dr BRA IRCH, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - Sunil Kumar
- Department of Surgical Oncology, Dr BRA IRCH, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - Ranjit Kumar Sahoo
- Department of Medical Oncology, Dr BRA IRCH, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| |
Collapse
|
|
10
|
Dunn C, Hong W, Gibbs P, Ackland S, Sjoquist K, Tebbutt NC, Price T, Burge M. Personalizing First-Line Systemic Therapy in Metastatic Colorectal Cancer: Is There a Role for Initial Low-Intensity Therapy in 2021 and Beyond? A Perspective From Members of the Australasian Gastrointestinal Trials Group. Clin Colorectal Cancer 2021; 20:245-255. [PMID: 34103264 DOI: 10.1016/j.clcc.2021.05.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 04/16/2021] [Accepted: 05/02/2021] [Indexed: 01/18/2023]
Abstract
Palliative chemotherapy is the cornerstone of treatment for the majority of patients with metastatic colorectal cancer, with the aim of increasing length and quality of life. Although guidelines outline the available treatment options in the first line, they provide limited guidance on choice and intensity of the chemotherapy backbone. Data from the TRIBE and TRIBE2 studies confirm a survival benefit with triplet FOLFOXIRI and bevacizumab, and this is a preferred option for younger patients with good performance status able to tolerate it. However, the relative benefit of a fluoropyrimidine doublet with oxaliplatin or irinotecan over single-agent fluoropyrimidine with or without a biologic is less certain; the available data demonstrate that single-agent fluoropyrimidine plus a biologic with planned sequencing of subsequent agents can produce similar overall survival outcomes with reduced toxicity. Our analysis of local real-world registry data suggests that this is an underutilized approach, particularly in younger and fitter patients. Established prognostic factors, including patient age, performance status, tumor sidedness, and biomarkers such as RAS/BRAF, are key in treatment selection; patients with left-sided RAS/BRAF wild-type disease or patients with low tumor bulk may be ideal for a less intensive regimen. Further studies are required to confirm the value of less-intensive regimens in the modern era, where the incorporation of biologic therapies has become routine and where non-chemotherapy options are emerging as viable options for molecularly defined patient subsets.
Collapse
Affiliation(s)
- Catherine Dunn
- Gibbs Lab, Personalised Medicine Division, Walter and Eliza Hall Institute, Melbourne, Victoria, Australia.
| | - Wei Hong
- Gibbs Lab, Personalised Medicine Division, Walter and Eliza Hall Institute, Melbourne, Victoria, Australia
| | - Peter Gibbs
- Gibbs Lab, Personalised Medicine Division, Walter and Eliza Hall Institute, Melbourne, Victoria, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia; Department of Medical Oncology, Western Health, Melbourne, Victoria, Australia
| | - Stephen Ackland
- Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia; Hunter Medical Research Institute, Newcastle, New South Wales, Australia
| | - Katrin Sjoquist
- NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia; Cancer Care Centre, St. George Hospital, Kogarah, New South Wales, Australia
| | - Niall C Tebbutt
- Department of Medical Oncology, Austin Health, Melbourne, Victoria, Australia; Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia
| | - Timothy Price
- Department of Medical Oncology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia
| | - Matthew Burge
- Department of Medical Oncology, Royal Brisbane Hospital, Herston, Queensland, Australia
| |
Collapse
|
|
11
|
Kang YH, Lee JS, Lee NH, Kim SH, Seo CS, Son CG. Coptidis Rhizoma Extract Reverses 5-Fluorouracil Resistance in HCT116 Human Colorectal Cancer Cells via Modulation of Thymidylate Synthase. Molecules 2021; 26:1856. [PMID: 33806077 PMCID: PMC8036817 DOI: 10.3390/molecules26071856] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 03/15/2021] [Accepted: 03/17/2021] [Indexed: 11/16/2022] Open
Abstract
Colorectal cancer (CRC) is a malignancy of the colon or rectum. It is ranked as the third most common cancer in both men and women worldwide. Early resection permitted by early detection is the best treatment, and chemotherapy is another main treatment, particularly for patients with advanced CRC. A well-known thymidylate synthase (TS) inhibitor, 5-fluorouracil (5-FU), is frequently prescribed to CRC patients; however, drug resistance is a critical limitation of its clinical application. Based on the hypothesis that Coptidis Rhizoma extract (CRE) can abolish this 5-FU resistance, we explored the efficacy and underlying mechanisms of CRE in 5-FU-resistant (HCT116/R) and parental HCT116 (HCT116/WT) cells. Compared to treatment with 5-FU alone, combination treatment with CRE and 5-FU drastically reduced the viability of HCT116/R cells. The cell cycle distribution assay showed significant induction of the G0/G1 phase arrest by co-treatment with CRE and 5-FU. In addition, the combination of CRE and 5-FU notably suppressed the activity of TS, which was overexpressed in HCT116/R cells, as compared to HCT116/WT cells. Our findings support the potential of CRE as an adjuvant agent against 5-FU-resistant colorectal cancers and indicate that the underlying mechanisms might involve inhibition of TS expression.
Collapse
Affiliation(s)
- Yong-Hwi Kang
- Institute of Bioscience & Integrative Medicine, Daejeon Oriental Hospital of Daejeon University, Daeduk-daero, Seo-gu, Daejeon 35353, Korea; (Y.-H.K.); (J.-S.L.)
| | - Jin-Seok Lee
- Institute of Bioscience & Integrative Medicine, Daejeon Oriental Hospital of Daejeon University, Daeduk-daero, Seo-gu, Daejeon 35353, Korea; (Y.-H.K.); (J.-S.L.)
| | - Nam-Hun Lee
- Department of Clinical Oncology, Cheonan Oriental Hospital of Daejeon University, 4, Notaesan-ro, Seobuk-gu, Cheonan-si 31099, Korea
| | - Seung-Hyung Kim
- Institute of Traditional Medicine & Bioscience, Daejeon University, Daehak-ro 62, Dong-gu, Daejeon 34520, Korea;
| | - Chang-Seob Seo
- Research Infrastructure Team, Herbal Medicine Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 34054, Korea;
| | - Chang-Gue Son
- Institute of Bioscience & Integrative Medicine, Daejeon Oriental Hospital of Daejeon University, Daeduk-daero, Seo-gu, Daejeon 35353, Korea; (Y.-H.K.); (J.-S.L.)
| |
Collapse
|
|
12
|
Dmello RS, To SQ, Chand AL. Therapeutic Targeting of the Tumour Microenvironment in Metastatic Colorectal Cancer. Int J Mol Sci 2021; 22:ijms22042067. [PMID: 33669775 PMCID: PMC7922123 DOI: 10.3390/ijms22042067] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 02/13/2021] [Accepted: 02/15/2021] [Indexed: 02/06/2023] Open
Abstract
Liver metastasis is the primary contributor to the death of patients with colorectal cancer. Despite the overall success of current treatments including targeted therapy, chemotherapy, and immunotherapy combinations in colorectal cancer patients, the prognosis of patients with liver metastasis remains poor. Recent studies have highlighted the importance of the tumour microenvironment and the crosstalk within that determines the fate of circulating tumour cells in distant organs. Understanding the interactions between liver resident cells and tumour cells colonising the liver opens new therapeutic windows for the successful treatment of metastatic colorectal cancer. Here we discuss critical cellular interactions within the tumour microenvironment in primary tumours and in liver metastases that highlight potential therapeutic targets. We also discuss recent therapeutic advances for the treatment of metastatic colorectal cancer.
Collapse
|
|
13
|
Huemer F, Piringer G, Schlintl V, Hackl H, Rinnerthaler G, Thaler J, Greil R, Weiss L. Hospitalizations and Clinical Outcome in Metastatic Colorectal Cancer During Regorafenib or TAS-102 Therapy. Cancers (Basel) 2020; 12:cancers12102812. [PMID: 33007814 PMCID: PMC7599669 DOI: 10.3390/cancers12102812] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 09/16/2020] [Accepted: 09/29/2020] [Indexed: 01/05/2023] Open
Abstract
Simple Summary Regorafenib and TAS-102 showed a survival benefit against placebo, and both drugs are approved for the treatment of metastatic colorectal cancer (mCRC) beyond second-line. The highly differential toxicity profile of both substances has led to a potentially biased perception of drug tolerability and complications—such as hospitalization—in the oncologic community. The aim of this retrospective analysis was to investigate hospitalization frequency during regorafenib and TAS-102 treatment and the impact of hospitalizations on survival. Treatment with regorafenib as well as a low Eastern Cooperative Oncology Group (ECOG) performance status turned out to be independent risk factors for hospitalization. Hospitalizations due to gastrointestinal toxicity were only seen with regorafenib. However, hospitalizations during regorafenib or TAS-102 treatment did not impact survival. In light of increased gastrointestinal toxicity leading to hospitalization during regorafenib treatment, we call for increased awareness to drug-specific toxicities, in order to prevent unnecessary complications by the early detection of adverse events and prompt counteraction. Abstract Current National Comprehensive Cancer Network (NCCN) and European Society of Medical Oncology (ESMO) guidelines recommend regorafenib or trifluridine/tipiracil (TAS-102) for the third-line therapy of metastatic colorectal cancer (mCRC). In this analysis, we evaluated hospitalizations during regorafenib or TAS-102 treatment and the impact of hospitalizations on overall survival (OS). This retrospective analysis was based on unselected, consecutive mCRC patients treated with regorafenib and/or TAS-102 at the tertiary cancer centers in Salzburg and Wels-Grieskirchen, Austria. Between January 2013 and May 2019, 93 patients started third- or fourth-line therapy with regorafenib or TAS-102. Tumor therapy (regorafenib versus TAS-102, HR: 1.95 [95% CI: 1.07–3.54], p = 0.03) and the Eastern Cooperative Oncology Group (ECOG) performance status (2–3 versus 0–1, HR: 4.04 [95% CI: 2.11–7.71], p < 0.001) showed a statistically significant association with hospitalization risk in multivariate analysis. The corresponding hospitalization probability from initiation of third- or fourth-line was 30% with regorafenib versus 18% with TAS-102 at five weeks and 41% versus 28% at ten weeks, respectively. Hospitalizations irrespective of cause during regorafenib or TAS-102 therapy did neither impact median survival in patients undergoing only third-line therapy (never-hospitalized: 5.7 months [95% CI: 3.9–10.5] versus hospitalized: 5.4 months [95% CI: 2.8–9.6], p = 0.45), nor in patients receiving third- and fourth-line therapy (12.2 months [95% CI: 10.6–28.8] versus 18.6 months [95% CI: 6.3-not reached], p = 0.90). In conclusion, apart from poor ECOG performance status, regorafenib therapy was associated with an increased hospitalization probability during palliative systemic third- and fourth-line therapy in mCRC. However, hospitalizations during regorafenib or TAS-102 therapy did not impact OS beyond second-line therapy.
Collapse
Affiliation(s)
- Florian Huemer
- Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Salzburg Cancer Research Institute—Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR), Center for Clinical Cancer and Immunology Trials (CCCIT), Paracelsus Medical University, 5020 Salzburg, Austria; (F.H.); (V.S.); (G.R.); (R.G.)
| | - Gudrun Piringer
- Department of Internal Medicine IV, Hematology and Oncology, Klinikum Wels-Grieskirchen, 4600 Wels, Austria; (G.P.); (J.T.)
- Johannes Kepler University Linz, 4040 Linz, Austria
| | - Verena Schlintl
- Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Salzburg Cancer Research Institute—Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR), Center for Clinical Cancer and Immunology Trials (CCCIT), Paracelsus Medical University, 5020 Salzburg, Austria; (F.H.); (V.S.); (G.R.); (R.G.)
| | - Hubert Hackl
- Division of Bioinformatics, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria;
| | - Gabriel Rinnerthaler
- Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Salzburg Cancer Research Institute—Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR), Center for Clinical Cancer and Immunology Trials (CCCIT), Paracelsus Medical University, 5020 Salzburg, Austria; (F.H.); (V.S.); (G.R.); (R.G.)
- Cancer Cluster Salzburg, 5020 Salzburg, Austria
| | - Josef Thaler
- Department of Internal Medicine IV, Hematology and Oncology, Klinikum Wels-Grieskirchen, 4600 Wels, Austria; (G.P.); (J.T.)
- Johannes Kepler University Linz, 4040 Linz, Austria
| | - Richard Greil
- Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Salzburg Cancer Research Institute—Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR), Center for Clinical Cancer and Immunology Trials (CCCIT), Paracelsus Medical University, 5020 Salzburg, Austria; (F.H.); (V.S.); (G.R.); (R.G.)
- Cancer Cluster Salzburg, 5020 Salzburg, Austria
| | - Lukas Weiss
- Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Salzburg Cancer Research Institute—Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR), Center for Clinical Cancer and Immunology Trials (CCCIT), Paracelsus Medical University, 5020 Salzburg, Austria; (F.H.); (V.S.); (G.R.); (R.G.)
- Cancer Cluster Salzburg, 5020 Salzburg, Austria
- Correspondence: ; Tel.: +43-57255-57892
| |
Collapse
|
|
14
|
Aedma SK, Chidharla A, Kelting S, Kasi A. Oxaliplatin-associated sarcoid-like reaction masquerading as recurrent colon cancer. BMJ Case Rep 2020; 13:e229548. [PMID: 32907862 PMCID: PMC7481089 DOI: 10.1136/bcr-2019-229548] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/04/2020] [Indexed: 11/04/2022] Open
Abstract
A 54-year-old man with stage IV B metastatic colorectal cancer with liver and peritoneal metastasis was treated with cytoreductive surgery (extended left colectomy, right partial hepatectomy, resection of right diaphragm nodule) and perioperative oxaliplatin-based chemotherapy. The patient was cancer-free for 6 months, at which point a surveillance positron emission tomography-CT scan showed metabolically active hepatosplenic lesions and mediastinal and bilateral hilar lymph nodes. An endobronchial ultrasound bronchoscopy-guided fine needle aspiration of the mediastinal and hilar lymph nodes revealed non-necrotising granulomas. The workup was negative for bacterial, fungal or mycobacterial infection, cancer or autoimmune disease. Carcinoembryonic antigen and COLVERA (a circulating tumour DNA liquid biopsy test for the detection of recurrent colon cancer) tests were negative. Subsequently the rare diagnosis of a sarcoidosis-like reaction from oxaliplatin-based chemotherapy was made. Repeat imaging after 3 months showed resolution of the hepatosplenic lesions and lymphadenopathy, alike.
Collapse
Affiliation(s)
| | - Anusha Chidharla
- Internal Medicine, University of Illinois College of Medicine at Peoria, Peoria, Illinois, USA
| | - Sarah Kelting
- Medical Oncology, University of Kansas Medical Center, Kansas City, Kansas, USA
| | - Anup Kasi
- Medical Oncology, University of Kansas Medical Center, Kansas City, Kansas, USA
| |
Collapse
|
|
15
|
Franko J, Brahmbhatt R, Tee M, Raman S, Ferrel B, Gorvet M, Andres M. Cellular Immunoprofile of Peritoneal Environment During a HIPEC Procedure. Ann Surg Oncol 2020; 27:5005-5013. [PMID: 32696309 DOI: 10.1245/s10434-020-08870-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2020] [Accepted: 06/27/2020] [Indexed: 12/18/2022]
Abstract
BACKGROUND We characterized the peritoneal immune cellular profile during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in this pilot study. METHODS We prospectively performed flow cytometric analysis of peritoneal fluid collected at laparotomy and during HIPEC at 0, 30, 60, and 90 min. Analysis consisted of standard flow cytometric leukocyte gating and the use of antibodies for stem cells, B lymphocytes, T-helper, T-suppressor, and natural killer (NK) cells. RESULTS The mean peritoneal carcinomatosis index (PCI) score was 19.8 ± 11.5 (median 19). Twelve patients had a completeness of cytoreduction (CCR) score of 0-1, and three patients had a CCR score of ≥ 2 (20%). The proportion of peritoneal NK cells remained stable (p = 0.655) throughout perfusion. The CD4/CD8 ratio (p = 0.019) and granulocyte/lymphocyte ratio (p = 0.018) evolved during cytoreduction, with no further change during HIPEC. Two distinct temporal patterns of peritoneal T lymphocytes became evident (the 'high' and 'low' CD4/CD8 ratio groups) and patients maintained their high versus low peritoneal CD4/CD8 ratio status throughout the duration of HIPEC. High CD4/CD8 was associated with longer cytoreduction (p = 0.019) and borderline higher PCI score (p = 0.058). No association was identified with age (p = 0.131), sex (p = 1.000), CCR status (p = 0.580), occurrence of complication (p = 0.282), or ascites volume (p = 0.713). CONCLUSION The cellular immunoprofile of peritoneal fluid during HIPEC is stable but changes during cytoreduction. Two distinct immune groups emerged, based on CD4/CD8 ratios in the peritoneal perfusate. Further studies are warranted to evaluate peritoneal immunity and the clinical significance of novel peritoneal immune phenotype.
Collapse
Affiliation(s)
- Jan Franko
- Division of Surgical Oncology, MercyOne Medical Center, Des Moines, IA, USA.
| | - Rushin Brahmbhatt
- Division of Surgical Oncology, MercyOne Medical Center, Des Moines, IA, USA
| | - May Tee
- Division of Surgical Oncology, MercyOne Medical Center, Des Moines, IA, USA
| | - Shankar Raman
- Division of Surgical Oncology, MercyOne Medical Center, Des Moines, IA, USA
| | - Benjamin Ferrel
- Division of Surgical Oncology, MercyOne Medical Center, Des Moines, IA, USA
| | - Marc Gorvet
- Division of Surgical Oncology, MercyOne Medical Center, Des Moines, IA, USA
| | - Matthew Andres
- Division of Surgical Oncology, MercyOne Medical Center, Des Moines, IA, USA.,Department of Pathology, MercyOne Medical Center, Des Moines, IA, USA
| |
Collapse
|
|
16
|
Nakano M, Kuromatsu R, Niizeki T, Okamura S, Iwamoto H, Shimose S, Shirono T, Noda Y, Kamachi N, Koga H, Torimura T. Primary Treatment with Molecular-Targeted Agents for Hepatocellular Carcinoma: A Propensity Score-matching Analysis. Hepatol Commun 2020; 4:1218-1228. [PMID: 32766480 PMCID: PMC7395064 DOI: 10.1002/hep4.1535] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 04/13/2020] [Accepted: 04/28/2020] [Indexed: 12/22/2022] Open
Abstract
Sorafenib and lenvatinib, as molecular-targeted agents, constitute effective primary treatment options for advanced hepatocellular carcinoma (HCC). However, the choice of optimal primary treatment agent remains controversial. Here, we aimed to assess the respective outcomes between these agents as primary treatment in patients with advanced HCC through use of propensity score-matching analysis (PSMA). We enrolled 670 consecutive patients who were diagnosed with advanced HCC and received sorafenib (n = 524) or lenvatinib (n = 146) as the primary treatment among 18 participating institutions between May 2009 and October 2019. To reduce confounding, we used PSMA regarding seven variables related to advanced HCC prognosis, resulting in the selection of 292 patients (n = 146 for each agent). Following PSMA, no significant difference was observed in the outcome of overall survival time between patients treated with sorafenib or lenvatinib (median survival time 15.3 or 14.9 months, respectively; P = 0.2358). Patients treated with lenvatinib exhibited significantly greater therapeutic effects (response rate: 5% and 31%; disease control rate: 46% and 69% for sorafenib and lenvatinib, respectively; P < 0.0001), but showed significantly lower probability of transition to secondary treatment (sorafenib, 60%; lenvatinib, 45%; P < 0.0269) and higher any adverse events rate (sorafenib, 86%; lenvatinib, 95%; P = 0.0207). Conclusion: As a primary molecular-targeted agent-based treatment for advanced HCC, our findings suggested that sorafenib is generally appropriate as it offers significantly lower frequency of adverse events and higher probability of transition to secondary treatment, in consideration of the enhanced postprogression survival mediated by sequential treatment. Alternatively, lenvatinib affords a significantly higher therapeutic effect and should be used when immediate tumor reduction is required.
Collapse
Affiliation(s)
- Masahito Nakano
- Division of Gastroenterology Department of Medicine Kurume University School of Medicine Kurume Japan
| | - Ryoko Kuromatsu
- Division of Gastroenterology Department of Medicine Kurume University School of Medicine Kurume Japan
| | - Takashi Niizeki
- Division of Gastroenterology Department of Medicine Kurume University School of Medicine Kurume Japan
| | - Shusuke Okamura
- Division of Gastroenterology Department of Medicine Kurume University School of Medicine Kurume Japan
| | - Hideki Iwamoto
- Division of Gastroenterology Department of Medicine Kurume University School of Medicine Kurume Japan
| | - Shigeo Shimose
- Division of Gastroenterology Department of Medicine Kurume University School of Medicine Kurume Japan
| | - Tomotake Shirono
- Division of Gastroenterology Department of Medicine Kurume University School of Medicine Kurume Japan
| | - Yu Noda
- Division of Gastroenterology Department of Medicine Kurume University School of Medicine Kurume Japan
| | - Naoki Kamachi
- Division of Gastroenterology Department of Medicine Kurume University School of Medicine Kurume Japan
| | - Hironori Koga
- Division of Gastroenterology Department of Medicine Kurume University School of Medicine Kurume Japan
| | - Takuji Torimura
- Division of Gastroenterology Department of Medicine Kurume University School of Medicine Kurume Japan
| | | |
Collapse
|
|
17
|
Keikes L, Koopman M, Stuiver MM, Lemmens VEPP, van Oijen MGH, Punt CJA. Practice variation on hospital level in the systemic treatment of metastatic colorectal cancer in The Netherlands: a population-based study. Acta Oncol 2020; 59:395-403. [PMID: 32048563 DOI: 10.1080/0284186x.2020.1722320] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Introduction: Population-based data on the implementation of guidelines for cancer patients in daily practice are scarce, while practice variation may influence patient outcomes. Therefore, we evaluated treatment patterns and associated variables in the systemic treatment of metastatic colorectal cancer (mCRC) in the Netherlands.Material and methods: We selected a random sample of adult mCRC patients diagnosed from 2008 to 2015 from the National Cancer Registry in 20 (4 academic, 8 teaching and 8 regional) Dutch hospitals. We examined the influence of patient, demographic and tumour characteristics on the odds of being treated with systemic therapy according to the current guideline and assessed its association with survival.Results: Our study population consisted of 2222 mCRC patients of whom 1307 patients received systemic therapy for mCRC. Practice variation was most obvious in the use of bevacizumab and anti-EGFR therapy in patients with (K)RAS wild-type tumours. Administration rates did not differ between hospital types but fluctuated between individual hospitals for bevacizumab (8-92%; p < .0001) and anti-EGFR therapy (10-75%; p = .05). Bevacizumab administration was inversely correlated to higher age (OR:0.2; 95%CI: 0.1-0.3) comorbidity (OR:0.6; 95%CI: 0.5-0.8) and the presence of metachronous metastases (OR:0.5; 95%CI: 0.3-0.7), but patient characteristics did not differ between hospitals with low or high bevacizumab administration rates. The hazard ratios for exposure to bevacizumab and anti-EGFR therapy were 0.8 (95%CI: 0.7-0.9) and 0.6 (95%CI: 0.5-0.8), respectively.Discussion: We identified significant inter-hospital variation in targeted therapy administration for mCRC patients, which may affect outcome. Age and comorbidity were inversely correlated with non-administration of bevacizumab but did not explain inter-hospital practice variation. Our data suggest that practice variation is based on individual strategy of hospitals rather than guideline recommendations or patient-driven decisions. Individual hospital strategies are an additional factor that may explain the observed differences between real-life data and results obtained from clinical trials.
Collapse
Affiliation(s)
- Lotte Keikes
- Department of Medical Oncology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Department of Research, Netherlands Comprehensive Cancer Organisation, Utrecht, The Netherlands
| | - Miriam Koopman
- Department of Medical Oncology, University Medical Centre, Utrecht University, Utrecht, The Netherlands
| | - Martijn M. Stuiver
- Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Valery E. P. P. Lemmens
- Department of Research, Netherlands Comprehensive Cancer Organisation, Utrecht, The Netherlands
| | - Martijn G. H. van Oijen
- Department of Medical Oncology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Department of Research, Netherlands Comprehensive Cancer Organisation, Utrecht, The Netherlands
| | - Cornelis J. A. Punt
- Department of Medical Oncology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| |
Collapse
|
|
18
|
FoxO3 reverses 5-fluorouracil resistance in human colorectal cancer cells by inhibiting the Nrf2/TR1 signaling pathway. Cancer Lett 2020; 470:29-42. [DOI: 10.1016/j.canlet.2019.11.042] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2019] [Revised: 10/28/2019] [Accepted: 11/30/2019] [Indexed: 12/30/2022]
|
|
19
|
Ooki A, Morita S, Iwamoto S, Hara H, Tanioka H, Satake H, Kataoka M, Kotaka M, Kagawa Y, Nakamura M, Shingai T, Ishikawa M, Miyake Y, Suto T, Hashiguchi Y, Yabuno T, Sakamoto J, Tsuji A, Ando M, Yamaguchi K. Patient-reported symptom burden as a prognostic factor in treatment with first-line cetuximab plus chemotherapy for unresectable metastatic colorectal cancer: Results of Phase II QUACK trial. Cancer Med 2020; 9:1779-1789. [PMID: 31962002 PMCID: PMC7050093 DOI: 10.1002/cam4.2826] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Revised: 12/13/2019] [Accepted: 12/22/2019] [Indexed: 12/21/2022] Open
Abstract
Background It remains unclear whether patients’ self‐perceptions of symptoms at baseline clinically impact the prognostic relevance, treatment efficacy, or toxicity profiles in metastatic colorectal cancer (mCRC) patients treated with the first‐line cetuximab and standard chemotherapy. Methods The data were collected from a prospective trial that assessed the relationships between quality of life (QOL), treatment efficacy, and adverse events (AEs). Results The analysis of 137 mCRC patients revealed a significant association between the presence of baseline tumor‐related symptoms and a lower overall survival (OS) compared to the absence of symptoms (HR, 2.49; 95% CI, 1.37‐4.62; P = .003). The asymptomatic responders had favorable outcomes compared to the symptomatic nonresponders (2‐year OS rates: 83.6% and 35.9%, respectively), while the symptomatic responders had similar outcomes to the asymptomatic nonresponders. The median postprogression survival differed significantly: 10.2 months for the symptomatic patients and 15.9 months for the asymptomatic patients (HR, 2.29; 95% CI, 1.25‐4.29, P = .008). The objective response rates and patient toxicity profiles were similar irrespective of the severity of baseline symptoms. Conclusion Baseline symptoms were associated with worse OS but not with impaired treatment efficacy or more frequent AEs in mCRC patients treated with cetuximab in addition to chemotherapy.
Collapse
Affiliation(s)
- Akira Ooki
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Satoshi Morita
- Department of Biomedical Statistics and Bioinformatics, Kyoto University, Kyoto, Japan
| | | | - Hiroki Hara
- Department of Gastroenterology, Saitama Cancer Center, Saitama, Japan
| | - Hiroaki Tanioka
- Department of Clinical Oncology, Kawasaki Medical School, Kurashiki, Japan
| | - Hironaga Satake
- Cancer Treatment Center, Kansai Medical University Hospital, Osaka, Japan
| | - Masato Kataoka
- Department of Surgery, National Hospital Organization Nagoya Medical Center, Nagoya, Japan
| | | | | | - Masato Nakamura
- Comprehensive Cancer Center, Aizawa Hospital, Matsumoto, Japan
| | - Tatsushi Shingai
- Department of Surgery, Osaka Saiseikai Senri Hospital, Suita, Japan
| | - Masashi Ishikawa
- Department of Surgery, Shikoku Central Hospital, Shikokuchuo, Japan
| | - Yasuhiro Miyake
- Department of Surgery, Osaka Minato Central Hospital, Osaka, Japan
| | - Takeshi Suto
- Department of Surgery, Yamagata Prefectural Central Hospital, Yamagata, Japan
| | - Yojiro Hashiguchi
- Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan
| | - Taichi Yabuno
- Department of Surgery, Yokohama Municipal Citizen's Hospital, Yokohama, Japan
| | | | - Akihito Tsuji
- Department of Medical Oncology, Kagawa University, Kita, Japan
| | - Masahiko Ando
- Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan
| | - Kensei Yamaguchi
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| |
Collapse
|
|
20
|
Multicenter phase II study of biweekly CAPIRI plus bevacizumab as second-line therapy in patients with metastatic colorectal cancer (JSWOG-C3 study). Int J Clin Oncol 2019; 24:1223-1230. [PMID: 31144145 PMCID: PMC6736909 DOI: 10.1007/s10147-019-01473-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2018] [Accepted: 05/18/2019] [Indexed: 12/22/2022]
Abstract
Background Triweekly capecitabine plus irinotecan (CAPIRI) was not a replacement for fluorouracil, leucovorin, and irinotecan (FOLFIRI) in the treatment of metastatic colorectal cancer (mCRC) because of the potential for greater toxicity. Recently, it has reported that mCAPIRI is well tolerated and non-inferior to FOLFIRI. In this study, we conducted a multicenter phase II trial to assess the efficacy and safety of biweekly CAPIRI plus bevacizumab as second-line chemotherapy for mCRC with reduced toxicity and preserved efficacy. Methods Patients with mCRC who had received prior chemotherapy, including oxaliplatin-based regimens, were eligible for this study. The treatment protocol administered capecitabine at 1000 mg/m2 twice daily from the evening of day 1 to the morning of day 8, intravenous irinotecan at 150 mg/m2 on day 1, and bevacizumab at 10 mg/kg on day 1 every 2 weeks. Primary endpoints for this study were progression-free survival (PFS) and safety. Secondary endpoints were overall survival (OS), time to treatment failure, response rate (RR), and disease control rate (DCR). Results Fifty-one patients were enrolled in this study. Median PFS was 5.5 months [95% confidence interval (CI) 4.23–7.40 months], and median OS was 13.5 months (95% CI 11.57–20.23 months). The RR was 14.6% (95% CI 6.5–28.4%), and the DCR was 66.7% (95% CI 51.5–79.2%). Hypertension was the most common Grade 3 adverse event (27.5%), followed by neutropenia (17.6%). Only two patients suffered from grade 3 hand–foot syndrome. Conclusions In mCRC patients, biweekly CAPIRI + bevacizumab appears effective and feasible as a second-line chemotherapy with relatively low toxicities, and has potential as a useful substitute for FOLFIRI + bevacizumab.
Collapse
|
|
21
|
Liu T, Wang X, Hu W, Fang Z, Jin Y, Fang X, Miao QR. Epigenetically Down-Regulated Acetyltransferase PCAF Increases the Resistance of Colorectal Cancer to 5-Fluorouracil. Neoplasia 2019; 21:557-570. [PMID: 31042625 PMCID: PMC6488821 DOI: 10.1016/j.neo.2019.03.011] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2019] [Revised: 03/22/2019] [Accepted: 03/26/2019] [Indexed: 12/22/2022] Open
Abstract
Only 10%–20% of colorectal cancer (CRC) patients observe effective responses to 5-fluorouracil (5-FU) based chemo-treatment. We used real-time PCR array and Western blot analysis to examine the expression alteration of acetyltransferases and deacetylases in 5-FU resistant CRC cell lines as compared to their respective parental CRC cell lines. Unlike other acetyltransferases and deacetylases, we found that the expression of acetyltransferase P300/CBP-associated factor (PCAF) is consistently decreased in three 5-FU resistant CRC cell lines. Similarly, knockdown of PCAF in HCT116 CRC parental cell line also increases the resistance to 5-FU and attenuates 5-FU-induced apoptosis. Mechanistically, we demonstrated that increased binding of trimethylated histone H3K27 in the promoter region of PCAF attenuated its transcription in 5-FU resistant HCT116/5-FU cells. Decreased PCAF impairs the acetylation of p53 and attenuates the p53-dependent transcription of p21, which results in the increased cyclin D1 and phosphorylation of Retinoblastoma 1. Conversely, overexpression of PCAF in CRC cell lines increases p21 and their susceptibility to 5-FU in vitro and in vivo. However, knockdown of p21 abolishes the beneficial effects of PCAF overexpression on increasing the sensitivity of HCT116/5-FU cells to 5-FU. Also, the reduced intensity of PCAF immunostaining was observed in the precancerous lesion, and microarray data from the public database further demonstrated the association between PCAF down-regulation and poor survival outcome. Our data suggest that PCAF-mediated p53 acetylation is an essential regulatory mechanism for increasing the susceptibility of CRC to 5-FU.
Collapse
Affiliation(s)
- Tong Liu
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital, Jilin University, 126 Xiantai Street, Changchun, Jilin 130033, China; Division of Pediatric Surgery, Department of Surgery, Children's Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI 53226, USA; Divisions of Pediatric Pathology, Department of Pathology, Children's Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI 53226, USA
| | - Xiang Wang
- Division of Pediatric Surgery, Department of Surgery, Children's Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI 53226, USA; Divisions of Pediatric Pathology, Department of Pathology, Children's Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI 53226, USA; New York University Winthrop Hospital, Mineola, NY 11501
| | - Wenquan Hu
- Division of Pediatric Surgery, Department of Surgery, Children's Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI 53226, USA; Divisions of Pediatric Pathology, Department of Pathology, Children's Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI 53226, USA; New York University Winthrop Hospital, Mineola, NY 11501
| | - Zhi Fang
- Division of Pediatric Surgery, Department of Surgery, Children's Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI 53226, USA; Divisions of Pediatric Pathology, Department of Pathology, Children's Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI 53226, USA; New York University Winthrop Hospital, Mineola, NY 11501
| | - Ying Jin
- Division of Pediatric Surgery, Department of Surgery, Children's Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI 53226, USA; Divisions of Pediatric Pathology, Department of Pathology, Children's Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI 53226, USA; Department of Breast Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, China
| | - Xuedong Fang
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital, Jilin University, 126 Xiantai Street, Changchun, Jilin 130033, China.
| | - Qing Robert Miao
- Division of Pediatric Surgery, Department of Surgery, Children's Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI 53226, USA; Divisions of Pediatric Pathology, Department of Pathology, Children's Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI 53226, USA; New York University Winthrop Hospital, Mineola, NY 11501.
| |
Collapse
|
|
22
|
Chiang CL, Choi HC, Lam KO, Chan BY, Lee SF, Yeung SY, Lau KS, Chan SY, Choy TS, Yuen KK. Real-world treatment patterns and outcomes in refractory metastatic colorectal cancer. Asia Pac J Clin Oncol 2019; 15 Suppl 2:5-13. [PMID: 30887726 DOI: 10.1111/ajco.13114] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
AIM To investigate treatment patterns and outcomes of metastatic colorectal cancer (mCRC) patients beyond second progression (PD2) since regorafenib and TAS-102 became available in Hong Kong. METHODS The clinical records of consecutive mCRC patients who were treated beyond PD2 at Department of Clinical Oncology, Queen Mary Hospital between June 2013 and February 2018, were retrospectively reviewed. RESULTS Of 176 PD2 patients (76.7% Eastern Cooperative Oncology Group performance status 0/1 and a median follow-up time of 6.6 [range, 0.4-37.2] months), 104 (59%) underwent palliative care only and 72 (41%) received active third-line (3L) treatment: regorafenib (n = 22), TAS-102 (n = 6), chemotherapy + antiepidermal growth factor receptor (n = 12), chemotherapy + antivascular endothelial growth factor (n = 28) or clinical trials (n = 4). Patients on active 3L treatment had significantly longer OS than those on palliative care only: 11.7 versus 5.5 months (adjusted hazard ratio = 0.41, 95% confidence interval: 0.28-0.61, P < 0.001). For those on active treatment, OS was significantly associated with the time from diagnosis of metastasis to PD2 (P < 0.001) and post-3L treatments (P = 0.009). When analyzing treatment eligibility according to trial criteria, half of the eligible patients (54/109) did not receive active treatment, but both eligible and ineligible patients achieved better OS when receiving active 3L treatment versus palliative care only (P < 0.001 and P = 0.002). No unexpected toxicity was reported. CONCLUSION Active 3L and beyond treatment significantly prolonged OS versus palliative care, even in selected "trial ineligible" patients. Given a high rate of palliation only care in eligible patients, improved patient access to medicine and counseling may be needed to maximize outcomes.
Collapse
Affiliation(s)
- C L Chiang
- Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.,Clinical Oncology Center, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.,Department of Clinical Oncology, Queen Mary Hospital, Hong Kong, China
| | - H C Choi
- Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - K O Lam
- Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.,Clinical Oncology Center, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.,Department of Clinical Oncology, Queen Mary Hospital, Hong Kong, China
| | - B Y Chan
- Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - S F Lee
- Department of Clinical Oncology, Tuen Mun Hospital, Hong Kong, China
| | - S Y Yeung
- Department of Clinical Oncology, Tuen Mun Hospital, Hong Kong, China
| | - K S Lau
- Department of Clinical Oncology, Queen Mary Hospital, Hong Kong, China
| | - S Y Chan
- Department of Clinical Oncology, Queen Mary Hospital, Hong Kong, China
| | - T S Choy
- Department of Clinical Oncology, Queen Mary Hospital, Hong Kong, China
| | - K K Yuen
- Department of Clinical Oncology, Queen Mary Hospital, Hong Kong, China
| |
Collapse
|
|
23
|
Wang T, Lin F, Sun X, Jiang L, Mao R, Zhou S, Shang W, Bi R, Lu F, Li S. HOXB8 enhances the proliferation and metastasis of colorectal cancer cells by promoting EMT via STAT3 activation. Cancer Cell Int 2019; 19:3. [PMID: 30622439 PMCID: PMC6317211 DOI: 10.1186/s12935-018-0717-6] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2018] [Accepted: 12/18/2018] [Indexed: 01/08/2023] Open
Abstract
Background Previous studies have demonstrated that the expression of homeobox8 (HOXB8) is higher in colorectal cancer (CRC) tissues than in normal tissues; however, the precise role of HOXB8 in human CRC cells remains to be elucidated. Methods We generated lentiviral constructs to overexpress and silence HOXB8 in CRC cell lines, and examined their biological functions through MTT, wound healing, colony and transwell, expression of signal transducer and activator of transcription 3 (STAT3) and epithelial–mesenchymal transition (EMT) related factors through western-blot. Results HOXB8 knockdown inhibited cellular proliferation and invasion in vitro as well as carcinogenesis and metastasis in vivo. HOXB8 also induced EMT, which is characterized by the down-regulation of E-cadherin and the up-regulation of Vimentin, N-cadherin, Twist, Zeb1 and Zeb2. Moreover, HOXB8 activated STAT3, which is known to play an oncogenic role in diverse human malignancies. Conclusions Our results indicate that HOXB8 may be an independent prognostic factor in CRC. Therefore, deserved a deeper research. Electronic supplementary material The online version of this article (10.1186/s12935-018-0717-6) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Tingting Wang
- 1Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Feiyan Lin
- 2Central Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Xuecheng Sun
- 1Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Lei Jiang
- 2Central Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Ruibo Mao
- 3Department of Colorectal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 Zhejiang China
| | - Shenyue Zhou
- 1Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Wenjing Shang
- 2Central Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Ruichun Bi
- 2Central Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Fengying Lu
- 2Central Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Shaotang Li
- 3Department of Colorectal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 Zhejiang China
| |
Collapse
|
|
24
|
Chambers AE, Frick J, Tanner N, Gerkin R, Kundranda M, Dragovich T. Chemotherapy re-challenge response rate in metastatic colorectal cancer. J Gastrointest Oncol 2018; 9:679-686. [PMID: 30151264 DOI: 10.21037/jgo.2018.04.08] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Background There are few treatment options in metastatic colorectal cancer (mCRC) after progression on standard chemotherapy. Third and fourth line therapies typically consist of regorafenib or trifluridine-tipiracil, however, clinical benefit of these medications is limited, as progression free survival is approximately 1.9 months for regorafenib (Grothey et al. 2013) and 2.0 months for trifluridine-tipiracil (Mayer et al. 2015). Another choice in this setting may include the re-initiation of previously used chemotherapy, therefore in this study we assessed the efficacy and tolerability of chemotherapy re-challenge. Methods This was a retrospective, cohort study assessing patients with mCRC who were 18-89 years of age and treated with re-challenge chemotherapy. Re-challenge chemotherapy was defined as re-initiation of oxaliplatin or irinotecan-based regimens at least nine months from the end of initial exposure. A minimum of four chemotherapy cycles was required to qualify as initial exposure. The key endpoints of this study were clinical benefit rate (CBR), defined as the proportion of patients with partial response or stable disease, and time to progression (TTP). Results A total of 67 chemotherapy re-challenges were accounted for in 51 patients. The overall CBR was 70.7%. Partial responses occurred in 50.7% cases. The TTP was 6.0 months. For the 51 cases of first re-challenge, the CBR was 75.5% and TTP was 6.5 months. Fourteen patients had a second re-challenge, and in these patients, the CBR was 61.5% and TTP was 4.1 months. Conclusions Oxaliplatin or irinotecan-based re-challenge should be considered as a third or fourth line treatment option in select patients with mCRC. CBR and especially TTP compare favorably to approved third line therapies such as regorafenib or trifluridine-tipiracil.
Collapse
Affiliation(s)
| | - Jacob Frick
- Department of Pharmacy, Banner MD Anderson Cancer Center, Gilbert, AZ, USA
| | - Natalee Tanner
- Department of Pharmacy, Banner MD Anderson Cancer Center, Gilbert, AZ, USA
| | - Richard Gerkin
- Graduate Medical Research, Banner-University Medical Center, Phoenix, AZ, USA
| | - Madappa Kundranda
- Gastrointestinal Medical Oncology, Department of Medicine, Banner MD Anderson Cancer Center, Gilbert, AZ, USA
| | - Tomislav Dragovich
- Medical Oncology, Department of Medicine, Banner MD Anderson Cancer Center, Gilbert, AZ, USA
| |
Collapse
|
|
25
|
Pellino G, Gallo G, Pallante P, Capasso R, De Stefano A, Maretto I, Malapelle U, Qiu S, Nikolaou S, Barina A, Clerico G, Reginelli A, Giuliani A, Sciaudone G, Kontovounisios C, Brunese L, Trompetto M, Selvaggi F. Noninvasive Biomarkers of Colorectal Cancer: Role in Diagnosis and Personalised Treatment Perspectives. Gastroenterol Res Pract 2018; 2018:2397863. [PMID: 30008744 PMCID: PMC6020538 DOI: 10.1155/2018/2397863] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2017] [Revised: 04/03/2018] [Accepted: 04/15/2018] [Indexed: 02/08/2023] Open
Abstract
Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide. It has been estimated that more than one-third of patients are diagnosed when CRC has already spread to the lymph nodes. One out of five patients is diagnosed with metastatic CRC. The stage of diagnosis influences treatment outcome and survival. Notwithstanding the recent advances in multidisciplinary management and treatment of CRC, patients are still reluctant to undergo screening tests because of the associated invasiveness and discomfort (e.g., colonoscopy with biopsies). Moreover, the serological markers currently used for diagnosis are not reliable and, even if they were useful to detect disease recurrence after treatment, they are not always detected in patients with CRC (e.g., CEA). Recently, translational research in CRC has produced a wide spectrum of potential biomarkers that could be useful for diagnosis, treatment, and follow-up of these patients. The aim of this review is to provide an overview of the newer noninvasive or minimally invasive biomarkers of CRC. Here, we discuss imaging and biomolecular diagnostics ranging from their potential usefulness to obtain early and less-invasive diagnosis to their potential implementation in the development of a bespoke treatment of CRC.
Collapse
Affiliation(s)
- Gianluca Pellino
- Unit of General Surgery, Department of Medical, Surgical, Neurological, Metabolic and Ageing Sciences, Università degli Studi della Campania “Luigi Vanvitelli”, Piazza Miraglia 2, 80138 Naples, Italy
- Colorectal Surgery Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain
| | - Gaetano Gallo
- Department of Medical and Surgical Sciences, OU of General Surgery, University of Catanzaro, Catanzaro, Italy
- Department of Colorectal Surgery, Clinic S. Rita, Vercelli, Italy
| | - Pierlorenzo Pallante
- Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Via S. Pansini 5, Naples, Italy
| | - Raffaella Capasso
- Department of Medicine and Health Sciences, University of Molise, Via Francesco de Sanctis 1, 86100 Campobasso, Italy
| | - Alfonso De Stefano
- Department of Abdominal Oncology, Division of Abdominal Medical Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, “Fondazione G. Pascale, ” IRCCS, Naples, Italy
| | - Isacco Maretto
- 1st Surgical Clinic, Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padua, Padua, Italy
| | - Umberto Malapelle
- Dipartimento di Sanità Pubblica, Università degli Studi di Napoli Federico II, Naples, Italy
| | - Shengyang Qiu
- Department of Colorectal Surgery, Royal Marsden Hospital, London, UK
| | - Stella Nikolaou
- Department of Colorectal Surgery, Royal Marsden Hospital, London, UK
| | - Andrea Barina
- 1st Surgical Clinic, Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padua, Padua, Italy
| | - Giuseppe Clerico
- Department of Colorectal Surgery, Clinic S. Rita, Vercelli, Italy
| | - Alfonso Reginelli
- Department of Internal and Experimental Medicine, Magrassi-Lanzara, Institute of Radiology, Università degli Studi della Campania “Luigi Vanvitelli”, Piazza Miraglia 2, 80138 Naples, Italy
| | - Antonio Giuliani
- Department of Medicine and Health Sciences “V. Tiberio”, University of Molise, Campobasso, Italy
| | - Guido Sciaudone
- Unit of General Surgery, Department of Medical, Surgical, Neurological, Metabolic and Ageing Sciences, Università degli Studi della Campania “Luigi Vanvitelli”, Piazza Miraglia 2, 80138 Naples, Italy
| | - Christos Kontovounisios
- Department of Colorectal Surgery, Royal Marsden Hospital, London, UK
- Department of Surgery and Cancer, Chelsea and Westminster Hospital Campus, Imperial College London, London, UK
| | - Luca Brunese
- Department of Medicine and Health Sciences, University of Molise, Via Francesco de Sanctis 1, 86100 Campobasso, Italy
| | - Mario Trompetto
- Department of Colorectal Surgery, Clinic S. Rita, Vercelli, Italy
| | - Francesco Selvaggi
- Unit of General Surgery, Department of Medical, Surgical, Neurological, Metabolic and Ageing Sciences, Università degli Studi della Campania “Luigi Vanvitelli”, Piazza Miraglia 2, 80138 Naples, Italy
| |
Collapse
|
|
26
|
Ahmed S, Iqbal M, Le D, Iqbal N, Pahwa P. Travel distance and use of salvage palliative chemotherapy in patients with metastatic colorectal cancer. J Gastrointest Oncol 2018; 9:269-274. [PMID: 29755765 DOI: 10.21037/jgo.2017.12.01] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Background Salvage palliative chemotherapy in metastatic colorectal cancer has been associated with significant improvement in survival. However, not all patients receive all available therapies. Travel burden can affect patient access and use of future therapy. The present study aims to determine relationship between travel distance (TD) and salvage palliative chemotherapy in patients with metastatic colorectal cancer. Method A patient cohort diagnosed with metastatic colorectal cancer during 2006-2010 in the province of Saskatchewan, Canada was studied. Logistic regression analyses were performed to assess relationship between travel distance and subsequent line therapies. Results The median age of 264 eligible patients was 62 years [interquartile range (IQR): 53-72]. The patients who received salvage systemic therapy had a median distance to travel of 60.0 km (IQR: 4.7-144) compared with 88.1 km (IQR: 4.8-189) if they did not receive second- or third-line therapy (P=0.06). In multivariate analysis distance to the cancer center <100 km, odds ratio (OR) 1.69 (95% CI: 1.003-2.84), no metastasectomy, OR 1.89 (95% CI: 1.03-3.46), and absence of comorbid illness as per Charlson comorbid index, OR 1.45 (95% CI: 1.19-1.77) were correlated with the use of second- and subsequent line therapies. Conclusions Our result revealed that travel distance to the cancer center greater than 100 km was associated less frequent use of second or subsequent line therapies in patients with metastatic colorectal cancer.
Collapse
Affiliation(s)
- Shahid Ahmed
- Saskatoon Cancer Center, Saskatchewan Cancer Agency, Saskatoon, Canada.,Division of Oncology, University of Saskatchewan, Saskatoon, Canada
| | | | - Duc Le
- Saskatoon Cancer Center, Saskatchewan Cancer Agency, Saskatoon, Canada.,Division of Oncology, University of Saskatchewan, Saskatoon, Canada
| | - Nayyer Iqbal
- Saskatoon Cancer Center, Saskatchewan Cancer Agency, Saskatoon, Canada.,Division of Oncology, University of Saskatchewan, Saskatoon, Canada
| | - Punam Pahwa
- Department of Community Health and Epidemiology, University of Saskatchewan, Saskatoon, Canada
| |
Collapse
|
|
27
|
Aparicio T, Ghiringhelli F, Boige V, Le Malicot K, Taieb J, Bouché O, Phelip JM, François E, Borel C, Faroux R, Dahan L, Jacquot S, Genet D, Khemissa F, Suc E, Desseigne F, Texereau P, Lepage C, Bennouna J. Bevacizumab Maintenance Versus No Maintenance During Chemotherapy-Free Intervals in Metastatic Colorectal Cancer: A Randomized Phase III Trial (PRODIGE 9). J Clin Oncol 2018; 36:674-681. [DOI: 10.1200/jco.2017.75.2931] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
Purpose Conflicting results are reported for maintenance treatment with bevacizumab during chemotherapy-free intervals (CFI) in metastatic colorectal cancer after induction chemotherapy. Patients and Methods In this open-label, phase III, randomized controlled trial, we compared the tumor control duration (TCD) observed with bevacizumab maintenance and with no treatment (observation) during CFI subsequent to induction chemotherapy with 12 cycles of fluorouracil, leucovorin, and irinotecan plus bevacizumab. After disease progression, the induction regimen was repeated for eight cycles, followed by a new CFI. Results From March 2010 to July 2013, 491 patients were randomly assigned. Disease progression or death occurred during induction chemotherapy in 85 patients (17%); 261 patients (53%) had at least one reinduction, 107 (22%) had two reinductions, and 56 (11%) had three or more reinductions. The median TCD was 15 months in both groups; the median progression-free survival (PFS) from randomization was 9.2 and 8.9 months in the maintenance group and observation groups, respectively. The TCD observed in both groups was higher compared with the TCD hypotheses of the trial. The median overall survival (OS) was 21.7 and 22.0 months in the maintenance and observation groups, respectively. In the per-protocol population, defined as patients with at least one reinduction after the first progression, the median duration of the first CFI was 4.3 months in both arms; the median TCD was 17.8 and 23.3 months ( P = .339), the median PFS was 9.9 and 9.5 months, and the median OS was 27.6 and 28.5 months in the maintenance and observation groups, respectively. Multivariable analysis revealed that female gender, WHO performance status ≥ 2, and unresected primary tumors were associated with a shorter TCD. Conclusion Bevacizumab maintenance monotherapy did not improve TCD, CFI duration, PFS, or OS.
Collapse
Affiliation(s)
- Thomas Aparicio
- Thomas Aparicio, Centre Hospitalier Universitaire (CHU) Saint Louis, Assistance Public Hôpitaux de Paris (APHP), and Université Paris 7, Sorbonne Paris Cité; Julien Taieb, Hôpital Européen Georges Pompidou, Paris; Francois Ghiringhelli, Centre Georges-François Leclerc; Karine Le Malicot, Fédération Francophone de Cancérologie Digestive; Come Lepage, CHU Le Bocage, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche (UMR) 1231, Dijon; Valérie Boige, Institut Gustave Roussy,
| | - Francois Ghiringhelli
- Thomas Aparicio, Centre Hospitalier Universitaire (CHU) Saint Louis, Assistance Public Hôpitaux de Paris (APHP), and Université Paris 7, Sorbonne Paris Cité; Julien Taieb, Hôpital Européen Georges Pompidou, Paris; Francois Ghiringhelli, Centre Georges-François Leclerc; Karine Le Malicot, Fédération Francophone de Cancérologie Digestive; Come Lepage, CHU Le Bocage, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche (UMR) 1231, Dijon; Valérie Boige, Institut Gustave Roussy,
| | - Valérie Boige
- Thomas Aparicio, Centre Hospitalier Universitaire (CHU) Saint Louis, Assistance Public Hôpitaux de Paris (APHP), and Université Paris 7, Sorbonne Paris Cité; Julien Taieb, Hôpital Européen Georges Pompidou, Paris; Francois Ghiringhelli, Centre Georges-François Leclerc; Karine Le Malicot, Fédération Francophone de Cancérologie Digestive; Come Lepage, CHU Le Bocage, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche (UMR) 1231, Dijon; Valérie Boige, Institut Gustave Roussy,
| | - Karine Le Malicot
- Thomas Aparicio, Centre Hospitalier Universitaire (CHU) Saint Louis, Assistance Public Hôpitaux de Paris (APHP), and Université Paris 7, Sorbonne Paris Cité; Julien Taieb, Hôpital Européen Georges Pompidou, Paris; Francois Ghiringhelli, Centre Georges-François Leclerc; Karine Le Malicot, Fédération Francophone de Cancérologie Digestive; Come Lepage, CHU Le Bocage, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche (UMR) 1231, Dijon; Valérie Boige, Institut Gustave Roussy,
| | - Julien Taieb
- Thomas Aparicio, Centre Hospitalier Universitaire (CHU) Saint Louis, Assistance Public Hôpitaux de Paris (APHP), and Université Paris 7, Sorbonne Paris Cité; Julien Taieb, Hôpital Européen Georges Pompidou, Paris; Francois Ghiringhelli, Centre Georges-François Leclerc; Karine Le Malicot, Fédération Francophone de Cancérologie Digestive; Come Lepage, CHU Le Bocage, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche (UMR) 1231, Dijon; Valérie Boige, Institut Gustave Roussy,
| | - Olivier Bouché
- Thomas Aparicio, Centre Hospitalier Universitaire (CHU) Saint Louis, Assistance Public Hôpitaux de Paris (APHP), and Université Paris 7, Sorbonne Paris Cité; Julien Taieb, Hôpital Européen Georges Pompidou, Paris; Francois Ghiringhelli, Centre Georges-François Leclerc; Karine Le Malicot, Fédération Francophone de Cancérologie Digestive; Come Lepage, CHU Le Bocage, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche (UMR) 1231, Dijon; Valérie Boige, Institut Gustave Roussy,
| | - Jean-Marc Phelip
- Thomas Aparicio, Centre Hospitalier Universitaire (CHU) Saint Louis, Assistance Public Hôpitaux de Paris (APHP), and Université Paris 7, Sorbonne Paris Cité; Julien Taieb, Hôpital Européen Georges Pompidou, Paris; Francois Ghiringhelli, Centre Georges-François Leclerc; Karine Le Malicot, Fédération Francophone de Cancérologie Digestive; Come Lepage, CHU Le Bocage, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche (UMR) 1231, Dijon; Valérie Boige, Institut Gustave Roussy,
| | - Eric François
- Thomas Aparicio, Centre Hospitalier Universitaire (CHU) Saint Louis, Assistance Public Hôpitaux de Paris (APHP), and Université Paris 7, Sorbonne Paris Cité; Julien Taieb, Hôpital Européen Georges Pompidou, Paris; Francois Ghiringhelli, Centre Georges-François Leclerc; Karine Le Malicot, Fédération Francophone de Cancérologie Digestive; Come Lepage, CHU Le Bocage, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche (UMR) 1231, Dijon; Valérie Boige, Institut Gustave Roussy,
| | - Christian Borel
- Thomas Aparicio, Centre Hospitalier Universitaire (CHU) Saint Louis, Assistance Public Hôpitaux de Paris (APHP), and Université Paris 7, Sorbonne Paris Cité; Julien Taieb, Hôpital Européen Georges Pompidou, Paris; Francois Ghiringhelli, Centre Georges-François Leclerc; Karine Le Malicot, Fédération Francophone de Cancérologie Digestive; Come Lepage, CHU Le Bocage, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche (UMR) 1231, Dijon; Valérie Boige, Institut Gustave Roussy,
| | - Roger Faroux
- Thomas Aparicio, Centre Hospitalier Universitaire (CHU) Saint Louis, Assistance Public Hôpitaux de Paris (APHP), and Université Paris 7, Sorbonne Paris Cité; Julien Taieb, Hôpital Européen Georges Pompidou, Paris; Francois Ghiringhelli, Centre Georges-François Leclerc; Karine Le Malicot, Fédération Francophone de Cancérologie Digestive; Come Lepage, CHU Le Bocage, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche (UMR) 1231, Dijon; Valérie Boige, Institut Gustave Roussy,
| | - Laetitia Dahan
- Thomas Aparicio, Centre Hospitalier Universitaire (CHU) Saint Louis, Assistance Public Hôpitaux de Paris (APHP), and Université Paris 7, Sorbonne Paris Cité; Julien Taieb, Hôpital Européen Georges Pompidou, Paris; Francois Ghiringhelli, Centre Georges-François Leclerc; Karine Le Malicot, Fédération Francophone de Cancérologie Digestive; Come Lepage, CHU Le Bocage, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche (UMR) 1231, Dijon; Valérie Boige, Institut Gustave Roussy,
| | - Stéphane Jacquot
- Thomas Aparicio, Centre Hospitalier Universitaire (CHU) Saint Louis, Assistance Public Hôpitaux de Paris (APHP), and Université Paris 7, Sorbonne Paris Cité; Julien Taieb, Hôpital Européen Georges Pompidou, Paris; Francois Ghiringhelli, Centre Georges-François Leclerc; Karine Le Malicot, Fédération Francophone de Cancérologie Digestive; Come Lepage, CHU Le Bocage, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche (UMR) 1231, Dijon; Valérie Boige, Institut Gustave Roussy,
| | - Dominique Genet
- Thomas Aparicio, Centre Hospitalier Universitaire (CHU) Saint Louis, Assistance Public Hôpitaux de Paris (APHP), and Université Paris 7, Sorbonne Paris Cité; Julien Taieb, Hôpital Européen Georges Pompidou, Paris; Francois Ghiringhelli, Centre Georges-François Leclerc; Karine Le Malicot, Fédération Francophone de Cancérologie Digestive; Come Lepage, CHU Le Bocage, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche (UMR) 1231, Dijon; Valérie Boige, Institut Gustave Roussy,
| | - Faiza Khemissa
- Thomas Aparicio, Centre Hospitalier Universitaire (CHU) Saint Louis, Assistance Public Hôpitaux de Paris (APHP), and Université Paris 7, Sorbonne Paris Cité; Julien Taieb, Hôpital Européen Georges Pompidou, Paris; Francois Ghiringhelli, Centre Georges-François Leclerc; Karine Le Malicot, Fédération Francophone de Cancérologie Digestive; Come Lepage, CHU Le Bocage, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche (UMR) 1231, Dijon; Valérie Boige, Institut Gustave Roussy,
| | - Etienne Suc
- Thomas Aparicio, Centre Hospitalier Universitaire (CHU) Saint Louis, Assistance Public Hôpitaux de Paris (APHP), and Université Paris 7, Sorbonne Paris Cité; Julien Taieb, Hôpital Européen Georges Pompidou, Paris; Francois Ghiringhelli, Centre Georges-François Leclerc; Karine Le Malicot, Fédération Francophone de Cancérologie Digestive; Come Lepage, CHU Le Bocage, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche (UMR) 1231, Dijon; Valérie Boige, Institut Gustave Roussy,
| | - Françoise Desseigne
- Thomas Aparicio, Centre Hospitalier Universitaire (CHU) Saint Louis, Assistance Public Hôpitaux de Paris (APHP), and Université Paris 7, Sorbonne Paris Cité; Julien Taieb, Hôpital Européen Georges Pompidou, Paris; Francois Ghiringhelli, Centre Georges-François Leclerc; Karine Le Malicot, Fédération Francophone de Cancérologie Digestive; Come Lepage, CHU Le Bocage, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche (UMR) 1231, Dijon; Valérie Boige, Institut Gustave Roussy,
| | - Patrick Texereau
- Thomas Aparicio, Centre Hospitalier Universitaire (CHU) Saint Louis, Assistance Public Hôpitaux de Paris (APHP), and Université Paris 7, Sorbonne Paris Cité; Julien Taieb, Hôpital Européen Georges Pompidou, Paris; Francois Ghiringhelli, Centre Georges-François Leclerc; Karine Le Malicot, Fédération Francophone de Cancérologie Digestive; Come Lepage, CHU Le Bocage, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche (UMR) 1231, Dijon; Valérie Boige, Institut Gustave Roussy,
| | - Come Lepage
- Thomas Aparicio, Centre Hospitalier Universitaire (CHU) Saint Louis, Assistance Public Hôpitaux de Paris (APHP), and Université Paris 7, Sorbonne Paris Cité; Julien Taieb, Hôpital Européen Georges Pompidou, Paris; Francois Ghiringhelli, Centre Georges-François Leclerc; Karine Le Malicot, Fédération Francophone de Cancérologie Digestive; Come Lepage, CHU Le Bocage, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche (UMR) 1231, Dijon; Valérie Boige, Institut Gustave Roussy,
| | - Jaafar Bennouna
- Thomas Aparicio, Centre Hospitalier Universitaire (CHU) Saint Louis, Assistance Public Hôpitaux de Paris (APHP), and Université Paris 7, Sorbonne Paris Cité; Julien Taieb, Hôpital Européen Georges Pompidou, Paris; Francois Ghiringhelli, Centre Georges-François Leclerc; Karine Le Malicot, Fédération Francophone de Cancérologie Digestive; Come Lepage, CHU Le Bocage, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche (UMR) 1231, Dijon; Valérie Boige, Institut Gustave Roussy,
| | | |
Collapse
|
|
28
|
Franko J. Therapeutic efficacy of systemic therapy for colorectal peritoneal carcinomatosis: Surgeon's perspective. Pleura Peritoneum 2018; 3:20180102. [PMID: 30911652 PMCID: PMC6405010 DOI: 10.1515/pp-2018-0102] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2018] [Accepted: 02/11/2018] [Indexed: 12/18/2022] Open
Abstract
Treatment choices for colorectal peritoneal carcinomatosis/metastases include systemic therapy and increasingly cytoreductive surgery with intraperitoneal chemotherapy delivery. These options are best considered as complementary and not exclusive alternatives. Two prospective randomized trials support use of peritonectomy procedures and intraperitoneal chemotherapy for colorectal peritoneal carcinomatosis. This overview examines efficacy, limitations and landscape of systemic therapy focusing on colorectal peritoneal carcinomatosis. Observations from literature support notions that (1) systemic therapy provides survival benefit for all prototypical patients with mCRC irrespective of metastatic disease site; (2) the magnitude of this benefit is considerably reduced among patients with peritoneal metastases who consequently experience significantly shorter overall survival; (3) efficacy of systemic therapy improved over time but at a slower pace for those with carcinomatosis; (4) this therapeutic difference has not diminished with introduction of targeted therapy, but perhaps widened; (5) further research of cytoreductive surgery and/or intraperitoneal regional therapies is thus a multidisciplinary responsibility of the entire oncology community; (6) peritonectomy procedures with intraperitoneal regional therapy are not scientifically supported in absence of systemic therapies.
Collapse
Affiliation(s)
- Jan Franko
- Chair of Surgical Oncology, Mercy Medical Center, 411 Laurel Street, Suite 2100, Des Moines, IA 50314, USA
| |
Collapse
|
|
29
|
Satake H, Tsuji A, Nakamura M, Ogawa M, Kotake T, Hatachi Y, Yasui H, Takagane A, Okita Y, Nakamura K, Onikubo T, Takeuchi M, Fujii M. Phase I study of primary treatment with 5-FU, oxaliplatin, irinotecan, levofolinate, and panitumumab combination chemotherapy in patients with advanced/recurrent colorectal cancer involving the wild-type RAS gene: the JACCRO CC-14 study. Int J Clin Oncol 2018; 23:490-496. [PMID: 29464396 PMCID: PMC5951897 DOI: 10.1007/s10147-017-1228-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2017] [Accepted: 12/15/2017] [Indexed: 12/22/2022]
Abstract
Background FOLFOXIRI is now regarded as the chemotherapy regimen that offers the best platform for the treatment of colorectal cancer. However, the safety and efficacy of FOLFOXIRI + panitumumab has not been demonstrated. We conducted a phase I study to determine the recommended dose of FOLFOXIRI + panitumumab as first-line treatment for RAS wild-type metastatic colorectal cancer (mCRC). Methods Patients received combination therapy consisting of panitumumab (6 mg/kg on day 1) + FOLFOXIRI [irinotecan (CPT-11), oxaliplatin (L-OHP) 85 mg/m2, and folinate (LV) 200 mg/m2] on day 1, followed by fluorouracil (5-FU) 3200 mg/m2 infused as a 46-h continuous infusion starting on day 1) repeated every 2 weeks as first-line treatment of RAS wild-type mCRC patients. A decrease in CPT-11 dose was planned (started at level 1: CPT-11 165 mg/m2). Results Seven patients were enrolled, and six were assessed for safety and efficacy. Maximum tolerated dose was not reached at level 1; all patients were treated at these levels. The common Grade 3 or 4 relevant toxicities were diarrhea (50%), hypokalemia (33%) and stomatitis (33%). No treatment-related deaths occurred. Of the six patients assessed four had partial response and the two others had stable disease; hence, the response rate was 66.7% (95% confidence interval 28.9–100%) and the disease control rate was 100%. Time to protocol treatment failure was 7.2 (1.4–7.3) months. Conclusion The FOLFOXIRI + panitumumab chemotherapy regimen was well tolerated by our patients with mCRC and showed promising anti-tumor activity. The recommended phase II dose was determined to be the same as the standard doses of this regimen used worldwide.
Collapse
Affiliation(s)
- Hironaga Satake
- Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Akihito Tsuji
- Department of Clinical Oncology, Kagawa University Faculty of Medicine-Kagawa University Hospital, 1750-1, Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan.
| | - Masato Nakamura
- Aizawa Comprehensive Cancer Center, Aizawa Hospital, Matsumoto, Japan
| | - Masaaki Ogawa
- Department of Surgery, Kazuno Kosei Hospital, Kazuno, Japan
| | - Takeshi Kotake
- Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Yukimasa Hatachi
- Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Hisateru Yasui
- Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Akinori Takagane
- Department of Surgery, Hakodate Goryoukaku Hospital, Hakodate, Japan
| | - Yoshihiro Okita
- Department of Clinical Oncology, Kagawa University Faculty of Medicine-Kagawa University Hospital, 1750-1, Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan
| | - Kumi Nakamura
- Aizawa Comprehensive Cancer Center, Aizawa Hospital, Matsumoto, Japan
| | - Toshihide Onikubo
- Aizawa Comprehensive Cancer Center, Aizawa Hospital, Matsumoto, Japan
| | - Masahiro Takeuchi
- Department of Clinical Medicine (Biostatistics), Kitasato University School of Pharmacy, Tokyo, Japan
| | - Masashi Fujii
- Japan Clinical Cancer Research Organization, Tokyo, Japan
| |
Collapse
|
|
30
|
Qiu T, Chen W, Li P, Sun J, Gu Y, Chen X. Subsequent anti-VEGF therapy after first-line anti-EGFR therapy improved overall survival of patients with metastatic colorectal cancer. Onco Targets Ther 2018; 11:465-471. [PMID: 29403291 PMCID: PMC5784580 DOI: 10.2147/ott.s149110] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Colorectal cancer is one of the leading causes of cancer deaths worldwide. Due to targeted therapy, overall survival (OS) of metastatic colorectal cancer (mCRC) patients has been significantly increased over the past decade. However, the best sequencing of the therapeutic agents to be used in RAS wild-type subgroup is still under research. To determine the efficacy of targeted therapy, we collected randomized controlled trials which included patients receiving anti-epidermal growth factor receptor (EGFR) monoclonal antibody as first-line therapy in RAS/KRAS wild-type mCRC. In our study, we found that OS was significantly improved by anti-vascular endothelial growth factor (VEGF) agent after first-line anti-EGFR therapy. Our results revealed that it is a sensible treatment strategy to try anti-VEGF agent after first-line combination therapy with anti-EGFR monoclonal antibody for RAS/KRAS wild-type mCRC.
Collapse
Affiliation(s)
- Tianzhu Qiu
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China
| | - Wensen Chen
- Infection Management Office, First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China
| | - Ping Li
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China
| | - Jing Sun
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China
| | - Yanhong Gu
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China
| | - Xiaofeng Chen
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China
| |
Collapse
|
|
31
|
Johnson B, Jin Z, Truty MJ, Smoot RL, Nagorney DM, Kendrick ML, Kipp BR, Grothey A. Impact of Metastasectomy in the Multimodality Approach for BRAF V600E Metastatic Colorectal Cancer: The Mayo Clinic Experience. Oncologist 2018; 23:128-134. [PMID: 28904173 PMCID: PMC5759813 DOI: 10.1634/theoncologist.2017-0230] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2017] [Accepted: 08/03/2017] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND BRAF V600E mutations are present in 8%-10% of patients with metastatic colorectal cancer (mCRC) and portend poor prognosis. This study investigated the impact of metastasectomy for patients with BRAF V600E mCRC. SUBJECTS, MATERIALS, AND METHODS Using prospective clinical and molecular data, patients with BRAF V600E mCRC were analyzed for clinical characteristics and survival. Statistical analyses utilized the Kaplan-Meier method, log-rank test, and Cox proportional hazard models. RESULTS Fifty-two patients were identified between July 1, 2008, and January 4, 2016. Patient characteristics included median age 65 years, 61% female, Eastern Cooperative Oncology Group performance status ≤1, 71% with right-sided tumors, and 28% with liver-limited metastasis. In the first-line setting, 7% (4/52) received fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI)/bevacizumab (BEV) and 81% were treated with doublet chemotherapy consisting of fluoropyrimidine, oxaliplatin, and BEV. Median overall survival (OS) for all 52 patients was 25 months with median progression-free survival (PFS) of 9.3 months. With median follow-up of 18.3 months, 21 patients underwent metastasectomy with longer OS (29.1 months vs. 22.7 months, hazard ratio [HR] = 0.33; confidence interval [CI], 0.12-0.78; p = .01) and PFS (13.6 months vs. 6.2 months, HR = 0.53, CI, 0.28-0.97; p = .03) compared with the non-metastasectomy cohort. In multivariate analysis, metastasectomy remained significant for improved survival outcomes (HR = 0.52; 95% CI, 0.07-1.02; p = .02). Median disease-free survival after metastasectomy was 9.7 months (95% CI, 5.5-19.5). Two patients remain disease-free at the time of last follow-up, with one patient without relapse for greater than 2 years (28.9 months). CONCLUSION Multimodality therapy incorporating metastasectomy for BRAF V600E mCRC should be considered and might be associated with improved overall survival in select patients. IMPLICATIONS FOR PRACTICE BRAF V600E metastatic colorectal cancer (mCRC) represents an extremely difficult molecular subset of colorectal cancer to treat. To date, this subset remains refractory to standard chemotherapies, prompting extensive clinical investigation regarding novel treatment approaches and targeted modalities. While the use of metastasectomy for expanded RAS wild-type and RAS mutated mCRC has resulted in improved overall survival for select patients, utilization of metastasectomy in patients with BRAF V600E mCRC remains controversial. This article explores the authors' experience with BRAF V600E mCRC to ascertain whether a multidisciplinary approach incorporating metastasectomy for well-selected patients improves overall survival.
Collapse
Affiliation(s)
- Benny Johnson
- Department of Medical Oncology, Mayo Clinic Cancer Center, Rochester, Minnesota, USA
| | - Zhaohui Jin
- Department of Medical Oncology, Mayo Clinic Cancer Center, Rochester, Minnesota, USA
| | - Mark J Truty
- Department of Surgical Oncology, Mayo Clinic Cancer Center, Rochester, Minnesota, USA
| | - Rory L Smoot
- Department of Surgical Oncology, Mayo Clinic Cancer Center, Rochester, Minnesota, USA
| | - David M Nagorney
- Department of Surgical Oncology, Mayo Clinic Cancer Center, Rochester, Minnesota, USA
| | - Michael L Kendrick
- Department of Surgical Oncology, Mayo Clinic Cancer Center, Rochester, Minnesota, USA
| | - Benjamin R Kipp
- Department of Anatomic Pathology, Mayo Clinic Cancer Center, Rochester, Minnesota, USA
| | - Axel Grothey
- Department of Medical Oncology, Mayo Clinic Cancer Center, Rochester, Minnesota, USA
| |
Collapse
|
|
32
|
Maroun J, Marginean H, Jonker D, Cripps C, Goel R, Asmis T, Goodwin R, Chiritescu G. A Phase I Study of Irinotecan, Capecitabine (Xeloda), and Oxaliplatin in Patients With Advanced Colorectal Cancer. Clin Colorectal Cancer 2017; 17:e257-e268. [PMID: 29330005 DOI: 10.1016/j.clcc.2017.12.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2017] [Revised: 11/13/2017] [Accepted: 12/07/2017] [Indexed: 10/18/2022]
Abstract
BACKGROUND The objective of the present phase I study was to define the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of irinotecan, capecitabine, and oxaliplatin given in combination (IXO regimen) to patients with previously untreated, unresectable advanced or metastatic colorectal cancer (CRC). PATIENTS AND METHODS Patients received oxaliplatin followed by irinotecan as intravenous infusions on day 1, with oral capecitabine taken twice daily (BID) on days 2 to 15 of a 3-week cycle. The dose ranges were explored as follows: oxaliplatin, 75 to 120 mg/m2; irinotecan, 160 to 230 mg/m2; capecitabine, 750 to 1000 mg/m2 BID. Dose escalation was performed individually for each drug at each dose level according to the type and severity of toxicity encountered in the previous cohort. RESULTS A total of 39 patients were enrolled at 7 dose levels and the MTD. The recommended doses for phase II evaluation were oxaliplatin 100 mg/m2, irinotecan 160 mg/m2, and capecitabine 950 mg/m2 BID. Diarrhea and febrile neutropenia were DLTs. Of the 39 enrolled patients, 26 (67%) had confirmed objective responses. The median progression-free survival was 11 months, and the median overall survival was 25 months. The survival rate at 5 years was 23%. CONCLUSION The IXO regimen has a manageable toxicity profile with promising antitumor activity as first-line treatment of advanced and metastatic CRC.
Collapse
Affiliation(s)
- Jean Maroun
- Department of Medicine, University of Ottawa, The Ottawa Hospital Regional Cancer Centre, Ottawa, ON, Canada
| | - Horia Marginean
- Clinical Research, The Ottawa Hospital Regional Cancer Centre, Ottawa, ON, Canada.
| | - Derek Jonker
- Division of Medical Oncology, Department of Medicine, University of Ottawa, The Ottawa Hospital Regional Cancer Centre, Ottawa, ON, Canada
| | - Christine Cripps
- Division of Medical Oncology, Department of Medicine, University of Ottawa, The Ottawa Hospital Regional Cancer Centre, Ottawa, ON, Canada
| | - Rakesh Goel
- Division of Medical Oncology, Department of Medicine, University of Ottawa, The Ottawa Hospital Regional Cancer Centre, Ottawa, ON, Canada
| | - Timothy Asmis
- Division of Medical Oncology, Department of Medicine, University of Ottawa, The Ottawa Hospital Regional Cancer Centre, Ottawa, ON, Canada
| | - Rachel Goodwin
- Division of Medical Oncology, Department of Medicine, University of Ottawa, The Ottawa Hospital Regional Cancer Centre, Ottawa, ON, Canada
| | - Gabriela Chiritescu
- Digestive Oncology Unit, Department of Gastroenterology, Universitair Ziekenhuis Leuven, Leuven, Belgium
| |
Collapse
|
|
33
|
Moriguchi M, Aramaki T, Nishiofuku H, Sato R, Asakura K, Yamaguchi K, Tanaka T, Endo M, Itoh Y. Sorafenib versus Hepatic Arterial Infusion Chemotherapy as Initial Treatment for Hepatocellular Carcinoma with Advanced Portal Vein Tumor Thrombosis. Liver Cancer 2017; 6:275-286. [PMID: 29234631 PMCID: PMC5704700 DOI: 10.1159/000473887] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
OBJECTIVE To investigate the validity of hepatic arterial infusion chemotherapy with low-dose 5-fluorouracil and cisplatin (LFP) versus sorafenib as first-line treatment for hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (Vp3, Vp4). PATIENTS AND METHODS We retrospectively reviewed the cases of Child-Pugh A advanced HCC with Vp3 or Vp4 treated with LFP or sorafenib between October 2002 and December 2013. RESULTS There were 32 patients in the LFP group and 14 patients in the sorafenib group. The objective response rate/disease control rate was 31.3/56.3% in the LFP group and 0/28.6% in the sorafenib group. The median survival time (MST) (309 vs. 120 days; p = 0.009) and the median time to treatment failure (109 vs. 37 days; p = 0.022) were significantly longer in the LFP group than in the sorafenib group. In the LFP group, a relatively favorable outcome (MST, 622 days) was obtained among the response cases. Among the nonresponse cases in the LFP group, at the time of cessation of LFP, 70.4% of cases were Child-Pugh A and 88.9% of cases maintained a score of ≤7 points; of the cases in whom Child-Pugh A was maintained, the survival period from the time of LFP discontinuation was significantly longer in the cases in whom sorafenib was introduced as a secondary treatment after LFP than in the cases treated with best supportive care (220 vs. 89 days; p = 0.002). The main adverse event with LFP was grade 3 or higher cytopenia, which was manageable, and adverse event-induced discontinuation was significantly lower as compared with sorafenib (p = 0.002). CONCLUSION For the treatment of HCC with Vp3/Vp4, it is desirable to initially use LFP and then immediately change to sorafenib if no response is obtained.
Collapse
Affiliation(s)
- Michihisa Moriguchi
- Division of Interventional Radiology, Shizuoka Cancer Center, Shizuoka, Japan,Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan,*Michihisa Moriguchi, MD, Assistant Professor, Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, 465 Kajii-cho, Kawaramachi-Hirokouji, Kamigyo-ku, Kyoto 602-8566 (Japan), E-Mail
| | - Takeshi Aramaki
- Division of Interventional Radiology, Shizuoka Cancer Center, Shizuoka, Japan
| | | | - Rui Sato
- Division of Interventional Radiology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Koiku Asakura
- Division of Diagnostic Radiology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Kanji Yamaguchi
- Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan
| | - Toshihiro Tanaka
- Department of Radiology, Nara Medical University, Kashihara, Japan
| | - Masahiro Endo
- Division of Diagnostic Radiology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Yoshito Itoh
- Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan
| |
Collapse
|
|
34
|
Sangha BS, Nimeiri H, Hickey R, Salem R, Lewandowski RJ. Radioembolization as a Treatment Strategy for Metastatic Colorectal Cancer to the Liver: What Can We Learn from the SIRFLOX Trial? Curr Treat Options Oncol 2017; 17:26. [PMID: 27098532 DOI: 10.1007/s11864-016-0402-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OPINION STATEMENT In the setting of liver metastases from colorectal cancer (CRC), radioembolization with yttrium-90 has been used to treat chemotherapy refractory disease with a growing interest to establish its efficacy in prospective trials combined with first- and second-line chemotherapy. SIRFLOX is an ongoing, multi-center, phase 3 randomized trial comparing first-line chemotherapy alone or in combination with yttrium-90 radioembolization in patients with CRC who have isolated liver metastases or liver-dominant metastases. Preliminary results from SIRFLOX demonstrate that radioembolization combined with first-line chemotherapy is safe and feasible. There was no significant difference in median overall progression-free survival (PFS) between the combined radioembolization-chemotherapy and chemotherapy-only arms (10.7 versus 10.2 months). Although the trial did not meet its primary endpoint of improved median PFS, there was a significant increase in the median hepatic PFS (20.5 versus 12.6 months; p = 0.02) favoring the combination arm. Thus, combining radioembolization with chemotherapy in the first-line setting may be most effective for liver-limited metastatic CRC. Since radioembolization targets liver disease, it is plausible that the trial failed to achieve an improvement in PFS given that 40 % of the SIRFLOX population had extra-hepatic disease. It is also possible that the overall median PFS may be a poor surrogate endpoint, and other endpoints like overall survival still needs to be delineated in this setting. In addition, it is crucial to document improvement or delay in time to deterioration in quality of life symptom endpoints in this population. SIRFLOX is the first of three prospective studies that assess the efficacy of adding radioembolization to first-line chemotherapy, and the combined data from these trials will provide the necessary power for an overall survival analysis. The final results of SIRFLOX will be eagerly awaited to determine if the increased hepatic PFS in preliminary data will translate to increased overall survival benefit.
Collapse
Affiliation(s)
- Bippan Singh Sangha
- Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, 676 N. St. Clair, Suite 800, Chicago, IL, 60611, USA
| | - Halla Nimeiri
- Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA
| | - Ryan Hickey
- Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, 676 N. St. Clair, Suite 800, Chicago, IL, 60611, USA
| | - Riad Salem
- Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, 676 N. St. Clair, Suite 800, Chicago, IL, 60611, USA
- Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA
- Division of Hepatology, Department of Medicine, Northwestern University, Chicago, IL, USA
| | - Robert J Lewandowski
- Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, 676 N. St. Clair, Suite 800, Chicago, IL, 60611, USA.
| |
Collapse
|
|
35
|
Gollins S, Moran B, Adams R, Cunningham C, Bach S, Myint AS, Renehan A, Karandikar S, Goh V, Prezzi D, Langman G, Ahmedzai S, Geh I. Association of Coloproctology of Great Britain & Ireland (ACPGBI): Guidelines for the Management of Cancer of the Colon, Rectum and Anus (2017) - Multidisciplinary Management. Colorectal Dis 2017; 19 Suppl 1:37-66. [PMID: 28632307 DOI: 10.1111/codi.13705] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
| | - Brendan Moran
- Basingstoke & North Hampshire Hospital, Basingstoke, UK
| | - Richard Adams
- Cardiff University and Velindre Cancer Centre, Cardiff, UK
| | | | - Simon Bach
- University of Birmingham and Queen Elizabeth Hospital, Birmingham, UK
| | | | - Andrew Renehan
- University of Manchester and Christie Hospital, Manchester, UK
| | | | - Vicky Goh
- King's College and Guy's & St Thomas' Hospital, London, UK
| | | | | | | | - Ian Geh
- Queen Elizabeth Hospital, Birmingham, UK
| |
Collapse
|
|
36
|
Is FOLFOXIRI alone or combined with targeted therapy administered as first-line treatment a reasonable choice for most patients with mCRC? Systematic review and network meta-analysis. Oncotarget 2017; 8:62339-62348. [PMID: 28977949 PMCID: PMC5617509 DOI: 10.18632/oncotarget.17725] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2017] [Accepted: 04/16/2017] [Indexed: 12/22/2022] Open
Abstract
Whether the intensive administration of folinic acid, 5-fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI) alone or combined with target therapy as first-line treatment could improve the prognosis of metastatic colorectal cancer (mCRC) patients is controversial. PubMed, the Cochrane Collaboration Central Register of Controlled Clinical Trials, Cochrane Systematic Reviews, ClinicalTrials.gov, the databases of conferences were queried to identify RCTs evaluating the efficacies and toxicities of intensive therapies used for first-line treatment of mCRC patients. The search included articles dated from the inception of these resources until March 31, 2017. We estimated HRs for OS and PFS and RRs for ORR, the R0 resection rate, and toxicities. Ten RCTs comprising 2,506 patients were included in this network meta-analysis. The PFS of patients administered FOLFOXIRI plus target therapy experienced prolonged PFS and OS and improved ORRs compared with FOLFOX/FOLFIRI plus target therapy (PFS: HR 0.71, 95% CI 0.59–0.86; OS: HR 0.81, 95% CI 0.69–0.94; ORR: RR 1.66, 95% CI 0.96–2.88; R0 resection rate: RR 2.66, 95% CI 1.86–3.82). There were no significant differences between PFS, OS, ORRs, or R0 resection rates and toxicities of patients administered FOLFOXIRI and FOLFOX/FOLFIRI plus target therapy. Further, FOLFOXIRI plus target therapy did not increase toxicities compared with FOLFOX/FOLFIRI plus target therapy. FOLFOXIRI plus target therapy when administered as first-line treatment of patients with mCRC is the best choice and did not increase toxicities. The patients with RAS/BRAF mutations could benefit from FOLFOXIRI plus Bev. FOLFOXIRI is as effective as FOLFOX/FOLFIRI plus target therapy.
Collapse
|
|
37
|
Price TJ, Thavaneswaran S, Burge M, Segelov E, Haller DG, Punt CJ, Arnold D, Karapetis CS, Tebbutt NC, Pavlakis N, Gibbs P, Shapiro JD. Update on optimal treatment for metastatic colorectal cancer from the ACTG/AGITG expert meeting: ECCO 2015. Expert Rev Anticancer Ther 2017; 16:557-71. [PMID: 27010906 DOI: 10.1586/14737140.2016.1170594] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
The treatment of metastatic CRC (mCRC) has evolved over the last 20 years, from fluoropyrimidines alone to combination chemotherapy and new biologic agents. Median overall survival is now over 24 months for RAS mutated (MT) patients and over 30 months for RAS wild-type (WT) patients. However, there are subgroups of patients with BRAF V600E MT CRC who have a significantly poorer outlook. Newer treatment options are also being explored in select subgroups of patients (anti-HER 2 in HER2 positive mCRC and immunotherapy in patients with defective mismatch repair (dMMR)). The best use of these systemic treatment options, as well as surgery in well-selected patients requires careful consideration of predictive biomarkers and importantly, the optimal sequence in which therapies should be given to derive maximal benefit. A group of colorectal subspecialty medical oncologists from Australia, USA, The Netherlands and Germany met during ECCO 2015 in Vienna to review current practice.
Collapse
Affiliation(s)
- Timothy J Price
- a Medical Oncology, The Queen Elizabeth Hospital , Adelaide Colorectal Tumour Group and University of Adelaide , Adelaide , Australia
| | | | - Matthew Burge
- c Medical Oncology, Royal Brisbane Hospital , Brisbane , Australia
| | - Eva Segelov
- d St Vincent's Clinical School, Faculty of Medicine , University of NSW , Sydney , Australia
| | - Daniel G Haller
- e Abramson Cancer Centre , University of Pennsylvania , Philadelphia , USA
| | - Cornelis Ja Punt
- f Academic Medical Center , University of Amsterdam , Amsterdam, The Netherlands
| | - Dirk Arnold
- g Medical Oncology, Klinik für Tumorbiologie , Freiburg , Germany
| | - Christos S Karapetis
- h Medical Oncology, Flinders Medical Centre , Flinders University and Adelaide Colorectal Tumour Group , Adelaide , Australia
| | | | - Nick Pavlakis
- j Medical Oncology, Royal Melbourne and Western Hospitals , Melbourne , Australia
| | - Peter Gibbs
- k Medical Oncology, Royal North Shore Hospital , Sydney University , Sydney , Australia
| | - Jeremy D Shapiro
- l Cabrini Medical Centre , Monash University , Melbourne , Australia
| |
Collapse
|
|
38
|
Salvatore L, Aprile G, Arnoldi E, Aschele C, Carnaghi C, Cosimelli M, Maiello E, Normanno N, Sciallero S, Valvo F, Beretta GD. Management of metastatic colorectal cancer patients: guidelines of the Italian Medical Oncology Association (AIOM). ESMO Open 2017; 2:e000147. [PMID: 28761730 PMCID: PMC5519792 DOI: 10.1136/esmoopen-2016-000147] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2016] [Revised: 01/18/2017] [Accepted: 01/20/2017] [Indexed: 01/05/2023] Open
Abstract
In the past 15 years, the outcome for patients with metastatic colorectal cancer has substantially improved owing to the availability of new cytotoxic and biological agents along with many significant advances in molecular selection, the use of personalised therapy and locoregional treatment, a more widespread sharing of specific professional experiences (multidisciplinary teams with oncologists, surgeons, radiotherapists, radiologists, biologists and pathologists), and the adoption of patient-centred healthcare strategies. The Italian Medical Oncology Association (AIOM) has developed evidence-based recommendations to help oncologists and all professionals involved in the management of patients with metastatic colorectal cancer in their daily clinical practice.
Collapse
Affiliation(s)
- Lisa Salvatore
- Department of Oncology, Azienda Ospedaliero-Universitaria Integrata di Verona, Verona, Italy
| | - Giuseppe Aprile
- Department of Oncology, Ospedale San Bortolo, Vicenza, Italy
| | - Ermenegildo Arnoldi
- Department of Oncology, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy
| | - Carlo Aschele
- Department of Oncology, ASL5 Liguria, La Spezia, Italy
| | - Carlo Carnaghi
- Department of Oncology, Humanitas Cancer Center, Rozzano (MI), Italy
| | - Maurizio Cosimelli
- Department of Oncologic Surgery, Istituto Nazionale Tumori Regina Elena, Roma, Italy
| | - Evaristo Maiello
- Department of Oncology, Ospedale Casa Sollievo Sofferenza, San Giovanni Rotondo, Puglia, Italy
| | - Nicola Normanno
- Department of Cell Biology and Biotherapies, Istituto Nazionale Tumori Fondazione G. Pascale IRCCS, Napoli, Italy
| | - Stefania Sciallero
- Department of Oncology, Azienda Ospedaliera S.Martino IRCCS, IST, Genova, Italy
| | - Francesca Valvo
- Department of Radiotherapy, Centro Nazionale di Adroterapia (CNAO), Pavia, Italy
| | | |
Collapse
|
|
39
|
Costa T, Nuñez J, Felismino T, Boente L, Mello C. REOX: Evaluation of the Efficacy of Retreatment With an Oxaliplatin-containing Regimen in Metastatic Colorectal Cancer: A Retrospective Single-center Study. Clin Colorectal Cancer 2017; 16:316-323. [PMID: 28392022 DOI: 10.1016/j.clcc.2017.03.002] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2016] [Revised: 02/20/2017] [Accepted: 03/01/2017] [Indexed: 11/15/2022]
Abstract
BACKGROUND Treatment of metastatic colorectal adenocarcinoma (mCRC) has evolved, and survival is over 30 months in contemporary trials. Nevertheless, there is a paucity of effective regimes after the first or second-line treatment. Thus, reexposure to previously used drugs has become a treatment strategy for some patients. We aimed to evaluate the efficacy of retreatment with an oxaliplatin-containing regimen in mCRC and correlate this with clinicopathologic features. PATIENTS AND METHODS We retrospectively analyzed 83 patients with mCRC who underwent reexposure to oxaliplatin (REOX). REOX was defined as a second trial of an oxaliplatin-containing regimen after a previous failure. Primary endpoint was time to treatment failure (TTF). RESULTS The median age was 53.5 years, and the female/male ratio was 51.8%/48.2%. The site of the primary tumor was colon (67.5%) and rectal (32.5%). KRAS was mutated in 39.8%. Liver-limited metastasis was found in 19.3% of patients. The main regimen was 5-fluorouracil, levoleucovorin, and oxaliplatin (mFOLFOX6) (84.3%). Bevacizumab and cetuximab were used in 42.2% and 6% of patients, respectively. REOX was used in the third and fourth lines in 48.2% and 25.3% of patients, respectively. The median TTF after REOX was 6.04 months. Overall survival (OS) was 10.04 months. Disease control (complete response + partial response + stable disease) was observed in 56.6%, whereas 42.2% had progressive disease. Partial response + complete response to previous oxaliplatin was predictive of prolonged OS. Patients who attained disease control had better median OS compared with those with progressive disease (14.5 vs. 6.24 months; P < .0001). CONCLUSION In the setting of heavily pretreated patients with mCRC, REOX was an effective treatment, with mTTF of 6.04 months in our cohort. Selection of patients with the longest time since previous oxaliplatin can translate in better outcome. Further studies should be conducted to confirm our data.
Collapse
Affiliation(s)
- Talita Costa
- Department of Medical Oncology, AC Camargo Cancer Center, Sao Paulo, Brazil
| | - Jose Nuñez
- Department of Medical Oncology, AC Camargo Cancer Center, Sao Paulo, Brazil
| | - Tiago Felismino
- Department of Medical Oncology, AC Camargo Cancer Center, Sao Paulo, Brazil
| | - Leonardo Boente
- Department of Medical Oncology, AC Camargo Cancer Center, Sao Paulo, Brazil
| | - Celso Mello
- Department of Medical Oncology, AC Camargo Cancer Center, Sao Paulo, Brazil.
| |
Collapse
|
|
40
|
Franko J, Shi Q, Meyers JP, Maughan TS, Adams RA, Seymour MT, Saltz L, Punt CJA, Koopman M, Tournigand C, Tebbutt NC, Diaz-Rubio E, Souglakos J, Falcone A, Chibaudel B, Heinemann V, Moen J, De Gramont A, Sargent DJ, Grothey A. Prognosis of patients with peritoneal metastatic colorectal cancer given systemic therapy: an analysis of individual patient data from prospective randomised trials from the Analysis and Research in Cancers of the Digestive System (ARCAD) database. Lancet Oncol 2016; 17:1709-1719. [PMID: 27743922 DOI: 10.1016/s1470-2045(16)30500-9] [Citation(s) in RCA: 464] [Impact Index Per Article: 51.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2016] [Revised: 08/25/2016] [Accepted: 08/25/2016] [Indexed: 12/18/2022]
Abstract
BACKGROUND Patients with peritoneal metastatic colorectal cancer have reduced overall survival compared with patients with metastatic colorectal cancer without peritoneal involvement. Here we further investigated the effect of the number and location of metastases in patients receiving first-line systemic chemotherapy. METHODS We analysed individual patient data for previously untreated patients enrolled in 14 phase 3 randomised trials done between 1997 and 2008. Trials were included if protocols explicitly pre-specified and solicited for patients with peritoneal involvement in the trial data collection process or had done a formal peritoneum-focused review of individual pre-treatment scans. We used stratified multivariable Cox models to assess the prognostic associations of peritoneal metastatic colorectal cancer with overall survival and progression-free survival, adjusting for other key clinical-pathological factors (age, sex, Eastern Cooperative Oncology Group (ECOG) performance score, primary tumour location [colon vs rectum], previous treatment, and baseline BMI). The primary endpoint was difference in overall survival between populations with and without peritoneal metastases. FINDINGS Individual patient data were available for 10 553 patients. 9178 (87%) of 10 553 patients had non-peritoneal metastatic colorectal cancer (4385 with one site of metastasis, 4793 with two or more sites of metastasis), 194 (2%) patients had isolated peritoneal metastatic colorectal cancer, and 1181 (11%) had peritoneal metastatic colorectal cancer and other organ involvement. These groups were similar in age, ethnic origin, and use of targeted treatment. Patients with peritoneal metastatic colorectal cancer were more likely than those with non-peritoneal metastatic colorectal cancer to be women (565 [41%] of 1371 vs 3312 [36%] of 9169 patients; p=0·0003), have colon primary tumours (1116 [84%] of 1334 patients vs 5603 [66%]; p<0·0001), and have performance status of 2 (136 [10%] vs 521 [6%]; p<0·0001). We recorded a higher proportion of patients with mutated BRAF in patients with peritoneal-only (eight [18%] of 44 patients with available data) and peritoneal metastatic colorectal cancer with other sites of metastasis (34 [12%] of 289), compared with patients with non-peritoneal metastatic colorectal cancer (194 [9%] of 2230; p=0·028 comparing the three groups). Overall survival (adjusted HR 0·75, 95% CI 0·63-0·91; p=0·003) was better in patients with isolated non-peritoneal sites than in those with isolated peritoneal metastatic colorectal cancer. Overall survival of patients with two of more non-peritoneal sites of metastasis (adjusted HR 1·04, 95% CI 0·86-1·25, p=0.69) and those with peritoneal metastatic colorectal cancer plus one other site of metastasis (adjusted HR 1·10, 95% CI 0·89-1·37, p=0·37) was similar to those with isolated peritoneal metastases. Compared with patients with isolated peritoneal metastases, those with peritoneal metastases and two or more additional sites of metastasis had the shortest survival (adjusted HR 1·40; CI 1·14-1·71; p=0·0011). INTERPRETATION Patients with peritoneal metastatic colorectal cancer have significantly shorter overall survival than those with other isolated sites of metastases. In patients with several sites of metastasis, poor survival is a function of both increased number of metastatic sites and peritoneal involvement. The pattern of metastasis and in particular, peritoneal involvement, results in prognostic heterogeneity of metastatic colorectal cancer. FUNDING None.
Collapse
Affiliation(s)
- Jan Franko
- Division of Surgical Oncology, Mercy Medical Center, Des Moines, IA, USA.
| | - Qian Shi
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA
| | - Jeffrey P Meyers
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA
| | | | | | - Matthew T Seymour
- Gastrointestinal Cancer Research Unit, Cookridge Hospital, Leeds, UK
| | - Leonard Saltz
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Cornelis J A Punt
- Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands
| | | | | | - Niall C Tebbutt
- Sydney Medical School, the University of Sydney, NSW, Australia
| | | | - John Souglakos
- University of Crete, School of Medicine, Heraklion, Greece
| | | | - Benoist Chibaudel
- Department of Medical Oncology, Franco-British Institute, Levallois-Perret, France
| | - Volker Heinemann
- University of Munich, Department of Medical Oncology and Comprehensive Cancer Center, Munich, Germany
| | - Joseph Moen
- Department of Biostatistics, University of Iowa, Iowa City, IA, USA
| | - Aimery De Gramont
- Department of Medical Oncology, Franco-British Institute, Levallois-Perret, France
| | - Daniel J Sargent
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA
| | - Axel Grothey
- Department of Oncology, Mayo Clinic, Rochester, MN, USA
| |
Collapse
|
|
41
|
Sartore-Bianchi A, Siena S, Tonini G, Bardelli A, Santini D. Overcoming dynamic molecular heterogeneity in metastatic colorectal cancer: Multikinase inhibition with regorafenib and the case of rechallenge with anti-EGFR. Cancer Treat Rev 2016; 51:54-62. [PMID: 27865140 DOI: 10.1016/j.ctrv.2016.10.006] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2016] [Revised: 10/21/2016] [Accepted: 10/23/2016] [Indexed: 12/25/2022]
Abstract
In metastatic colorectal cancer (mCRC), fluorouracil-based combination therapy with oxaliplatin or irinotecan is the mainstay of first-line treatment. Patient survival has been significantly improved with the introduction of monoclonal antibodies against VEGF (bevacizumab), VEGFR2 (ramucirumab) or EGFR (cetuximab or panitumumab) in first- and second-line therapies. However, all patients treated with chemotherapy and targeted therapies will eventually relapse, and recently the emergence of alterations in EGFR, RAS, BRAF, ERB-B2, MET and possibly in other genes has been shown to jeopardize response to EGFR blockade. In chemorefractory patients, multikinase inhibition with regorafenib has proved to be effective and rechallenge with chemotherapy or anti-EGFR agents is empirically pursued. This review will critically discuss how the evolving knowledge of mechanisms of resistance driven by intratumoural dynamic molecular heterogeneity can impact on rational choice of treatments in this setting.
Collapse
Affiliation(s)
- Andrea Sartore-Bianchi
- Department of Hematology and Oncology, Niguarda Cancer Center, Ospedale Niguarda, 20162 Milan, Italy
| | - Salvatore Siena
- Department of Hematology and Oncology, Niguarda Cancer Center, Ospedale Niguarda, 20162 Milan, Italy; Department of Oncology, Università degli Studi di Milano, 20122 Milan, Italy
| | - Giuseppe Tonini
- Department of Medical Oncology, Campus Bio-Medico University of Rome, 00128 Rome, Italy
| | - Alberto Bardelli
- Candiolo Cancer Institute-FPO, IRCCS, 10060 Candiolo, Torino, Italy; Department of Oncology, University of Torino, 10043 Torino, Italy
| | - Daniele Santini
- Department of Medical Oncology, Campus Bio-Medico University of Rome, 00128 Rome, Italy.
| |
Collapse
|
|
42
|
Dadduzio V, Basso M, Rossi S, Cenci T, Capodimonti S, Strippoli A, Orlandi A, Cerchiaro E, Schinzari G, Cassano A, Martini M, Barone C. KRAS Exon 2 Mutations as Prognostic Indicators in Advanced Colorectal Cancer in Clinical Practice: A Mono-Institutional Study. Mol Diagn Ther 2016; 20:65-74. [PMID: 26610798 DOI: 10.1007/s40291-015-0178-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND Kirsten-Ras (KRAS) mutations are widely accepted negative predictive factors for anti-EGFR therapies in metastatic colorectal cancer (mCRC), while their prognostic significance is still under discussion. OBJECTIVE This mono-institutional retrospective study aims to investigate the real-life impact of exon 2 codon 12 and 13 mutations in mCRC. METHODS All mCRC patients treated at our institution between 2008 and 2014 carrying KRAS exon 2 mutations were included. The primary endpoint was to determine any significant difference in overall survival (OS) between codon 12 and 13 mutations. Secondary endpoints included progression-free survival (PFS), OS in both populations according to antiangiogenic treatment, and OS in liver-limited disease (LLD). RESULTS Of 620 mCRC patients, 218 carried KRAS exon 2 mutations (35.1%): 162 (26.1%) at codon 12 and 56 (9.0 %) at codon 13. Median OS results were similar: 32.0 months (codon 12) and 31.0 months (codon 13). PFS was also comparable, reaching 10.8 months in both populations. The addition of bevacizumab to chemotherapy conferred a trend toward survival advantage in codon 12 but not codon 13 mutation (p = 0.058). A high proportion of LLD patients underwent hepatic surgery with radical purpose (62.3%): in these patients, median OS has not yet been reached, while OS in non-LLD patients was 30.2 months. CONCLUSIONS No difference in OS between KRAS codon 12/13 mutated disease was found. This analysis showed a very prolonged OS for KRAS-mutated patients, even when LLD patients were excluded; OS of our real-life series favorably compares with OS of all-RAS wild-type patients in recent randomized studies.
Collapse
Affiliation(s)
- Vincenzo Dadduzio
- Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy.
| | - Michele Basso
- Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Sabrina Rossi
- Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Tonia Cenci
- Pathology Unit, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Sara Capodimonti
- Pathology Unit, Università Cattolica del Sacro Cuore, Rome, Italy
| | | | - Armando Orlandi
- Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy
| | | | | | | | - Maurizio Martini
- Pathology Unit, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Carlo Barone
- Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy
| |
Collapse
|
|
43
|
Ho M, Renouf D, Cheung W, Lim H, Speers C, Zhou C, Kennecke H. Patterns of practice with third-line anti-EGFR antibody for metastatic colorectal cancer. Curr Oncol 2016; 23:329-333. [PMID: 27803597 PMCID: PMC5081009 DOI: 10.3747/co.23.3030] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Therapy with anti-epidermal growth factor receptor (egfr) monoclonal antibody improves outcomes for patients with metastatic colorectal cancer (mcrc) in the first-, second-, and third-line trial settings. In British Columbia, the use of egfr inhibitors (egfris) is confined to third-line therapy, which might lower the proportion of patients who receive this therapy. The objective of the present study was to describe egfri treatment patterns when those agents are limited to the third-line setting. The results will inform decisions about optimal use of egfri agents, including earlier in the course of therapy for metastatic disease. METHODS All patients with newly diagnosed mcrc who were referred to BC Cancer Agency clinics in 2009 were included in the study. Prognostic and treatment information was prospectively collected; KRAS test results were determined by chart review. RESULTS The study included 443 patients with a median age of 66 years. For the 321 patients who received systemic therapy, median survival was 22.3 months. Of the 117 patients who were treated with 5-fluorouracil, oxaliplatin, and irinotecan, and who were potentially eligible for egfri therapy, 90% (105 patients) were tested for KRAS status. Of the 60 patients with KRAS wild-type tumours, 82% (49 patients) received egfri therapy. CONCLUSIONS When egfri therapy is limited to the third-line setting, only a small proportion of patients receive such therapy, with death and poor performance status preventing its use in the rest. Availability of egfri in earlier lines of therapy could increase the proportion of patients treated with all active systemic agents.
Collapse
Affiliation(s)
- M.Y. Ho
- Cross Cancer Institute and University of Alberta, Edmonton, AB
| | - D.J. Renouf
- BC Cancer Agency and University of British Columbia, Vancouver, BC
| | - W.Y. Cheung
- BC Cancer Agency and University of British Columbia, Vancouver, BC
| | - H.J. Lim
- BC Cancer Agency and University of British Columbia, Vancouver, BC
| | - C.H. Speers
- BC Cancer Agency and University of British Columbia, Vancouver, BC
| | - C. Zhou
- BC Cancer Agency and University of British Columbia, Vancouver, BC
| | - H.F. Kennecke
- BC Cancer Agency and University of British Columbia, Vancouver, BC
| |
Collapse
|
|
44
|
Artaç M, Coşkun HŞ, Dane F, Karabulut B, Korkmaz L, Karaağaç M, Çabuk D, Karabulut S, Faruk Aykan N, Doruk H, Avcı N, Turhal NS. Benefit of Bevacizumab-Based Frontline Therapy in Patients with Metastatic Colorectal Cancer (mCRC): a Turkish Oncology Group Study. J Gastrointest Cancer 2016; 47:264-72. [PMID: 27126591 DOI: 10.1007/s12029-016-9823-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Several chemotherapy regimens using bevacizumab have been developed. Our goal was to investigate regimens that have demonstrated significant clinical activity in patients with metastatic colorectal cancer (mCRC). MATERIALS AND METHODS Six hundred and sixty six patients with mCRC who received first-line chemotherapy combination with bevacizumab were studied. Fluoropyrimidine (F) plus irinotecan (I)-based (FI-bev), F plus oxaliplatin (O)-based (FO-bev), and F-based (F-bev) treatment regimens were compared with respect to progression-free survival (PFS) and overall survival (OS). RESULTS The median PFS of FI-bev (n = 414) was 10.9 months (95 % CI 10-11.8), of FO-bev (n = 211) was 9.4 months (95 % CI 8.3-10.4), and of F-bev (n = 41) was 9.5 months (95 % CI 5.9-13.1) (p = 0.089). The median OS of FI-bev was 26.3 months (95 % CI 21.7-30.9), of FO-bev was 27 months (95 % CI 24.3-29.7), and of F-bev was 23.3 months (95 % CI 12.7-33.9) (p = 0.102). In KRAS wild-type patients, the median PFS of FI-bev group was significantly longer than FO-bev group (10.5 vs. 9.1 months, p = 0.006). The FI-bev group had better OS than FO-bev group with borderline significance (p = 0.058). The FI-bev group had significantly longer OS than F-bev group. Patients who underwent metastasectomy or those with Eastern Cooperative Oncology Group performance status (ECOG-PS) ≤1 had longer PFS and OS independent of the type of chemotherapy regimen. CONCLUSION FI-bev may be the preferred frontline regimen for patients with KRAS wild-type mCRC. Metastasectomy and performance score were the strongest positive predictors of OS and PFS regardless of backbone chemotherapy regimen.
Collapse
Affiliation(s)
- Mehmet Artaç
- Department of Medical Oncology, Necmettin Erbakan University, Meram Medical Faculty, 42080, Konya, Turkey.
| | - Hasan Şenol Coşkun
- Department of Medical Oncology, Akdeniz University Faculty of Medicine, Antalya, Turkey
| | - Faysal Dane
- Department of Medical Oncology, Marmara University Faculty of Medicine, Istanbul, Turkey
| | - Bülent Karabulut
- Department of Medical Oncology, Ege University Faculty of Medicine, Izmir, Turkey
| | - Levent Korkmaz
- Department of Medical Oncology, Necmettin Erbakan University, Meram Medical Faculty, 42080, Konya, Turkey
| | - Mustafa Karaağaç
- Department of Medical Oncology, Necmettin Erbakan University, Meram Medical Faculty, 42080, Konya, Turkey
| | - Devrim Çabuk
- Department of Medical Oncology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey
| | - Senem Karabulut
- Department of Medical Oncology, Istanbul University, Istanbul Medical Faculty, Istanbul, Turkey
| | - Nuri Faruk Aykan
- Department of Medical Oncology, Istanbul University, Istanbul Medical Faculty, Istanbul, Turkey
| | - Hatice Doruk
- Department of Medical Oncology, Acıbadem Bursa Hospital, Bursa, Turkey
| | - Nilüfer Avcı
- Department of Medical Oncology, Ali Osman Sönmez Oncology Hospital, Bursa, Turkey
| | | |
Collapse
|
|
45
|
Masuishi T, Taniguchi H, Hamauchi S, Komori A, Kito Y, Narita Y, Tsushima T, Ishihara M, Todaka A, Tanaka T, Yokota T, Kadowaki S, Machida N, Ura T, Fukutomi A, Ando M, Onozawa Y, Tajika M, Yasui H, Muro K, Mori K, Yamazaki K. Regorafenib Versus Trifluridine/Tipiracil for Refractory Metastatic Colorectal Cancer: A Retrospective Comparison. Clin Colorectal Cancer 2016; 16:e15-e22. [PMID: 27670892 DOI: 10.1016/j.clcc.2016.07.019] [Citation(s) in RCA: 57] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2016] [Revised: 07/19/2016] [Accepted: 07/28/2016] [Indexed: 01/11/2023]
Abstract
BACKGROUND Regorafenib and trifluridine/tipiracil (TAS-102) both prolong survival for patients with refractory metastatic colorectal cancer. However, it is unclear which drug should be administered first. MATERIALS AND METHODS We retrospectively evaluated the data from patients who had received regorafenib or TAS-102 at 2 institutions from May 2013 to March 2015. The inclusion criteria were disease refractory or intolerant to fluoropyrimidines, oxaliplatin, irinotecan, anti-vascular endothelial growth factor antibodies, and anti-epidermal growth factor receptor (EGFR) antibodies (if KRAS exon 2 wild-type), and no previous treatment with regorafenib or TAS-102. RESULTS A total of 146 and 54 patients received regorafenib and TAS-102, respectively. The baseline characteristics were similar between the 2 groups, except for a history of irinotecan and anti-EGFR therapy and high alkaline phosphatase levels. The median progression-free survival and overall survival were 2.1 months and 6.7 months, respectively, with regorafenib and 2.1 months and 6.5 months, respectively, with TAS-102 (progression-free survival hazard ratio 1.20, P = .27; overall survival hazard ratio, 1.01, P = .97). The analysis of overall survival for patients after the approval of TAS-102 in Japan was similar to the overall survival for the entire population. The frequency of hand-foot syndrome and increased aspartate aminotransferase, alanine aminotransferase, and bilirubin levels was higher and the frequency of neutropenia, leukopenia, anemia, nausea, and febrile neutropenia was lower with regorafenib than with TAS-102. No remarkable differences were found in the efficacy and safety of TAS-102 between patients with and without previous regorafenib and vice versa. CONCLUSION Regorafenib and TAS-102 had similar efficacy but resulted in different toxicities, which could guide the agent choice.
Collapse
Affiliation(s)
- Toshiki Masuishi
- Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Hiroya Taniguchi
- Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
| | - Satoshi Hamauchi
- Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Azusa Komori
- Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Yosuke Kito
- Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Yukiya Narita
- Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Takahiro Tsushima
- Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Makoto Ishihara
- Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Akiko Todaka
- Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Tsutomu Tanaka
- Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Tomoya Yokota
- Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Shigenori Kadowaki
- Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Nozomu Machida
- Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Takashi Ura
- Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Akira Fukutomi
- Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Masashi Ando
- Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Yusuke Onozawa
- Division of Clinical Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Masahiro Tajika
- Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Hirofumi Yasui
- Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Kei Muro
- Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Keita Mori
- Clinical Research Center, Shizuoka Cancer Center, Shizuoka, Japan
| | - Kentaro Yamazaki
- Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| |
Collapse
|
|
46
|
Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D, Aranda Aguilar E, Bardelli A, Benson A, Bodoky G, Ciardiello F, D'Hoore A, Diaz-Rubio E, Douillard JY, Ducreux M, Falcone A, Grothey A, Gruenberger T, Haustermans K, Heinemann V, Hoff P, Köhne CH, Labianca R, Laurent-Puig P, Ma B, Maughan T, Muro K, Normanno N, Österlund P, Oyen WJG, Papamichael D, Pentheroudakis G, Pfeiffer P, Price TJ, Punt C, Ricke J, Roth A, Salazar R, Scheithauer W, Schmoll HJ, Tabernero J, Taïeb J, Tejpar S, Wasan H, Yoshino T, Zaanan A, Arnold D. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol 2016; 27:1386-422. [PMID: 27380959 DOI: 10.1093/annonc/mdw235] [Citation(s) in RCA: 2362] [Impact Index Per Article: 262.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2016] [Accepted: 05/31/2016] [Indexed: 02/11/2024] Open
Abstract
Colorectal cancer (CRC) is one of the most common malignancies in Western countries. Over the last 20 years, and the last decade in particular, the clinical outcome for patients with metastatic CRC (mCRC) has improved greatly due not only to an increase in the number of patients being referred for and undergoing surgical resection of their localised metastatic disease but also to a more strategic approach to the delivery of systemic therapy and an expansion in the use of ablative techniques. This reflects the increase in the number of patients that are being managed within a multidisciplinary team environment and specialist cancer centres, and the emergence over the same time period not only of improved imaging techniques but also prognostic and predictive molecular markers. Treatment decisions for patients with mCRC must be evidence-based. Thus, these ESMO consensus guidelines have been developed based on the current available evidence to provide a series of evidence-based recommendations to assist in the treatment and management of patients with mCRC in this rapidly evolving treatment setting.
Collapse
Affiliation(s)
- E Van Cutsem
- Digestive Oncology, University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium
| | - A Cervantes
- Medical Oncology Department, INCLIVA University of Valencia, Valencia, Spain
| | - R Adam
- Hepato-Biliary Centre, Paul Brousse Hospital, Villejuif, France
| | - A Sobrero
- Medical Oncology, IRCCS San Martino Hospital, Genova, Italy
| | - J H Van Krieken
- Research Institute for Oncology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
| | - D Aderka
- Division of Oncology, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel
| | - E Aranda Aguilar
- Medical Oncology Department, University Hospital Reina Sofia, Cordoba, Spain
| | - A Bardelli
- School of Medicine, University of Turin, Turin, Italy
| | - A Benson
- Division of Hematology/Oncology, Northwestern Medical Group, Chicago, USA
| | - G Bodoky
- Department of Oncology, St László Hospital, Budapest, Hungary
| | - F Ciardiello
- Division of Medical Oncology, Seconda Università di Napoli, Naples, Italy
| | - A D'Hoore
- Abdominal Surgery, University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium
| | - E Diaz-Rubio
- Medical Oncology Department, Hospital Clínico San Carlos, Madrid, Spain
| | - J-Y Douillard
- Medical Oncology, Institut de Cancérologie de l'Ouest (ICO), St Herblain
| | - M Ducreux
- Department of Medical Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | - A Falcone
- Department of Medical Oncology, University of Pisa, Pisa, Italy Division of Medical Oncology, Department of Oncology, University Hospital 'S. Chiara', Istituto Toscano Tumori, Pisa, Italy
| | - A Grothey
- Division of Medical Oncology, Mayo Clinic, Rochester, USA
| | - T Gruenberger
- Department of Surgery I, Rudolfstiftung Hospital, Vienna, Austria
| | - K Haustermans
- Department of Radiation Oncology, University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium
| | - V Heinemann
- Comprehensive Cancer Center, University Clinic Munich, Munich, Germany
| | - P Hoff
- Instituto do Câncer do Estado de São Paulo, University of São Paulo, São Paulo, Brazil
| | - C-H Köhne
- Northwest German Cancer Center, University Campus Klinikum Oldenburg, Oldenburg, Germany
| | - R Labianca
- Cancer Center, Ospedale Giovanni XXIII, Bergamo, Italy
| | - P Laurent-Puig
- Digestive Oncology Department, European Hospital Georges Pompidou, Paris, France
| | - B Ma
- Department of Clinical Oncology, Prince of Wales Hospital, State Key Laboratory in Oncology in South China, Chinese University of Hong Kong, Shatin, Hong Kong
| | - T Maughan
- CRUK/MRC Oxford Institute for Radiation Oncology, Gray Laboratories, University of Oxford, Oxford, UK
| | - K Muro
- Department of Clinical Oncology and Outpatient Treatment Center, Aichi Cancer Center Hospital, Nagoya, Japan
| | - N Normanno
- Cell Biology and Biotherapy Unit, I.N.T. Fondazione G. Pascale, Napoli, Italy
| | - P Österlund
- Helsinki University Central Hospital, Comprehensive Cancer Center, Helsinki, Finland Department of Oncology, University of Helsinki, Helsinki, Finland
| | - W J G Oyen
- The Institute of Cancer Research and The Royal Marsden Hospital, London, UK
| | - D Papamichael
- Department of Medical Oncology, Bank of Cyprus Oncology Centre, Nicosia, Cyprus
| | - G Pentheroudakis
- Department of Medical Oncology, University of Ioannina, Ioannina, Greece
| | - P Pfeiffer
- Department of Oncology, Odense University Hospital, Odense, Denmark
| | - T J Price
- Haematology and Medical Oncology Unit, Queen Elizabeth Hospital, Woodville, Australia
| | - C Punt
- Department of Medical Oncology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
| | - J Ricke
- Department of Radiology and Nuclear Medicine, University Clinic Magdeburg, Magdeburg, Germany
| | - A Roth
- Digestive Tumors Unit, Geneva University Hospitals (HUG), Geneva, Switzerland
| | - R Salazar
- Catalan Institute of Oncology (ICO), Barcelona, Spain
| | - W Scheithauer
- Department of Internal Medicine I and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
| | - H J Schmoll
- Department of Internal Medicine IV, University Clinic Halle, Martin-Luther-University Halle-Wittenberg, Halle, Germany
| | - J Tabernero
- Medical Oncology Department, Vall d' Hebron University Hospital, Vall d'Hebron Institute of Oncology (V.H.I.O.), Barcelona, Spain
| | - J Taïeb
- Digestive Oncology Department, European Hospital Georges Pompidou, Paris, France
| | - S Tejpar
- Digestive Oncology, University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium
| | - H Wasan
- Department of Cancer Medicine, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - T Yoshino
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan
| | - A Zaanan
- Digestive Oncology Department, European Hospital Georges Pompidou, Paris, France
| | - D Arnold
- Instituto CUF de Oncologia (ICO), Lisbon, Portugal
| |
Collapse
|
|
47
|
Tamburini E, Rudnas B, Santelmo C, Drudi F, Gianni L, Nicoletti SVL, Ridolfi C, Tassinari D. Maintenance based Bevacizumab versus complete stop or continuous therapy after induction therapy in first line treatment of stage IV colorectal cancer: A meta-analysis of randomized clinical trials. Crit Rev Oncol Hematol 2016; 104:115-23. [PMID: 27338848 DOI: 10.1016/j.critrevonc.2016.05.016] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2015] [Revised: 03/31/2016] [Accepted: 05/25/2016] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND In stage IV colorectal cancer, bevacizumab-based maintenance therapy, complete stop therapy and continuous therapy are considered all possible approaches after first line induction chemotherapy. However, there are no clear data about which approach is preferable. MATERIAL AND METHODS All randomized phase III trials comparing bevacizumab-based maintenance therapy (MB) with complete stop therapy (ST) or with continuous therapy (CT) were considered eligible and included into the analysis. Primary endpoint was the Time to failure strategies (TFS). Secondary endpoints were Overall Survival (OS) and Progression free survival (PFS). Meta-analysis was performed in line with the PRISMA statement. RESULTS 1892 patients of five trials were included into the analysis. A significant improvement in TFS (HR 0.79; CI 95% 0.7-0.9 p=0.0005) and PFS (HR 0.56; CI 95% 0.44-0.71 p<0.00001) were observed in favour of MB versus ST. A trend, but not statistically significant, in favour of MB versus ST was also observed for OS (HR 0.88; CI 95% 0.77-1.01, p=0.08). Comparing maintenance therapy versus continuous therapy no statistically differences were observed in the outcomes evaluated (OS 12 months OR 1.1 p=0.62, OS 24 months OR 1 p=1, OS 36 months OR 0.54 p=0.3, TFS 12 months OR 0.76 p=0.65). CONCLUSIONS Our meta-analysis suggests that use of MB approach increases TFS, PFS compared to ST. Although without observing any statistically advantage, it should be highlighted that MB versus ST showed a trend in favour of MB. We observed no difference between MB and CT. MB should be considered the standard regimen in patients with stage IV colorectal cancer after first line induction therapy.
Collapse
Affiliation(s)
| | - Britt Rudnas
- Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | | | | | | | | | | | | |
Collapse
|
|
48
|
McLean J, Rho YS, Kuruba G, Mamo A, Gilabert M, Kavan T, Panasci L, Melnychuk D, Batist G, Kavan P. Clinical Practice Patterns in Chemotherapeutic Treatment Regimens for Metastatic Colorectal Cancer. Clin Colorectal Cancer 2016; 15:135-40. [DOI: 10.1016/j.clcc.2015.10.003] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2015] [Revised: 10/02/2015] [Accepted: 10/05/2015] [Indexed: 01/05/2023]
|
|
49
|
Rosati G, Aprile G, Cardellino GG, Avallone A. A review and assessment of currently available data of the EGFR antibodies in elderly patients with metastatic colorectal cancer. J Geriatr Oncol 2016; 7:134-41. [DOI: 10.1016/j.jgo.2016.01.006] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2015] [Revised: 01/16/2016] [Accepted: 01/29/2016] [Indexed: 12/15/2022]
|
|
50
|
Liu J, Xu J. Clinical value of capecitabine maintenance therapy after first-line combination chemotherapy in patients with unresectable stage Ⅳ rectal cancer. Shijie Huaren Xiaohua Zazhi 2016; 24:467-473. [DOI: 10.11569/wcjd.v24.i3.467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the efficacy and safety of capecitabine maintenance therapy after first-line combination chemotherapy in patients with unresectable stage Ⅳ rectal cancer.
METHODS: Fifty-three patients with unresectable stage Ⅳ advanced rectal cancer who achieved clinical response after first-line chemotherapy (FOLFOX or FOLFIRI, q2w, 12 cycles) from June 2011 to June 2014 at the People's Hospital of Ji'an City were randomly divided into two groups: A and B. Group A (28 patients) received maintenance therapy with capecitabine (1000 mg/m2, po, bid, d1-14, q21d). Group B (25 patients) did not receive any further chemotherapy. Progression-free survival (PFS) and adverse reactions were compared between the two groups.
RESULTS: The 28 patients treated with capecitabine maintenance therapy achieved a median progression free survival (PFS) of around 11.6 mo, significantly longer than the value (6.5 mo) in the 25 patients who did not receive maintenance treatment (P < 0.05). The response rate (RR) after first-line chemotherapy was 39.2% in the maintenance group and 32% in the non-maintenance group (P > 0.05). The adverse effects were reduced significantly in the maintenance therapy group and control group compared with those in first-line combination chemotherapy (P < 0.05). There was no statistical difference in adverse effects between the maintenance treatment and observation groups except for hand-foot syndrome and pigmentation (P > 0.05).
CONCLUSION: Patients with unresectable stage Ⅳ rectal cancer could benefit from capeciabine maintenance therapy in terms of longer PFS, better tolerance and milder adverse reactions.
Collapse
|