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Lim SH, Kim MJ, Lee J, Lim HY, Kang WK, Kim ST. The Impact of Pembrolizumab as a Salvage Therapy Based on HER2 Expression in Advanced Gastric Cancer. Cancers (Basel) 2024; 16:2969. [PMID: 39272827 PMCID: PMC11393848 DOI: 10.3390/cancers16172969] [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: 06/22/2024] [Revised: 08/22/2024] [Accepted: 08/23/2024] [Indexed: 09/15/2024] Open
Abstract
Immune checkpoint inhibitors (ICIs) are used as salvage treatments for advanced gastric cancer (AGC) regardless of HER2 status. This study assessed the efficacy of ICIs based on HER2 expression in AGC patients who received pembrolizumab as salvage monotherapy at Samsung Medical Center from November 2017 to March 2023. HER2 status was determined via immunohistochemistry, and tumor response and survival outcomes were compared accordingly. Among the 113 patients analyzed, with a median age of 61 years and 64.6% being male, 12 patients (10.6%) were HER2-positive, and 101 patients (89.4%) were HER2-negative. Of 92 evaluable patients, none had a complete response. However, 50% of HER2-positive patients had a partial response, compared to 4.9% of HER2-negative patients (p < 0.001). The disease control rate was 70% in HER2-positive and 37.8% in HER2-negative patients (p = 0.086). Median progression-free survival was 5.53 months for HER2-positive patients versus 1.81 months for HER2-negative patients (p = 0.037). Pembrolizumab as a salvage chemotherapy for the treatment of AGC demonstrated superior effectiveness in HER2-positive patients compared with HER2-negative patients.
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Affiliation(s)
- Sung Hee Lim
- Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Seoul 06351, Republic of Korea
| | - Min Jung Kim
- Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Seoul 06351, Republic of Korea
| | - Jeeyun Lee
- Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Seoul 06351, Republic of Korea
| | - Ho Yeong Lim
- Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Seoul 06351, Republic of Korea
| | - Won Ki Kang
- Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Seoul 06351, Republic of Korea
| | - Seung Tae Kim
- Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Seoul 06351, Republic of Korea
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Kawabata R, Chin K, Takahari D, Hosaka H, Muto O, Shindo Y, Nagata N, Yabusaki H, Imamura H, Endo S, Kashiwada T, Nakamura M, Hihara J, Kobayashi M, Sagawa T, Saito S, Sato A, Yamada T, Okano N, Shimada K, Matsushima M, Kataoka M, Matsumoto S, Goto M, Kotaka M, Shiraishi T, Yamai H, Nagashima F, Ishizuka N, Yamaguchi K. Multicenter phase II study of capecitabine plus oxaliplatin in older patients with advanced gastric cancer: the Tokyo Cooperative Oncology Group (TCOG) GI-1601 study. Gastric Cancer 2023; 26:1020-1029. [PMID: 37610558 PMCID: PMC10640487 DOI: 10.1007/s10120-023-01423-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Accepted: 08/07/2023] [Indexed: 08/24/2023]
Abstract
BACKGROUND Capecitabine plus oxaliplatin (CapeOX) is a standard treatment option for advanced gastric cancer (AGC). We conducted a prospective multicenter phase II study to evaluate the efficacy and safety of CapeOX as a first-line therapy for AGC in older patients. METHODS Chemotherapy-naive patients aged ≥ 70 years with AGC were eligible. Initial treatment comprised capecitabine (2000 mg/m2 on days 1-14) and oxaliplatin (130 mg/m2 on day 1) every 3 weeks. After the initial feasibility assessment, the dose was reduced considering toxicity (capecitabine, 1500 mg/m2 on days 1-14; and oxaliplatin, 100 mg/m2 on day 1 every 3 weeks). The primary endpoint was overall survival (OS). RESULTS In total, 108 patients were enrolled, of whom 104 were evaluated. Thirty-nine patients received the original-dose treatment, whereas 65 received the reduced-dose treatment. The median OS, progression-free survival (PFS), and time to treatment failure (TTF) were 12.9 (95% CI 11.6-14.8), 5.7 (95% CI 5.0-7.0), and 4.3 (95% CI 3.9-5.7) months, respectively, for all patients; 13.4 (95% CI 9.5-16.0), 5.8 (95% CI 4.1-7.8), and 5.3 (95% CI 3.5-7.2) months in the original-dose group; and 12.8 (95% CI 11.3-15.3), 5.7 (95% CI 4.4-7.0), and 4.1 (95% CI 3.7-5.7) months in the reduced-dose group. The most common grade 3/4 toxicities were neutropenia (17.9%), anemia (12.8%), and thrombocytopenia (12.8%) in the original-dose group and neutropenia (13.8%) and anorexia (12.3%) in the reduced-dose group. CONCLUSIONS These findings demonstrate CapeOX's efficacy and safety in older AGC patients.
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Affiliation(s)
- Ryohei Kawabata
- Department of Surgery, Osaka Rosai Hospital, Nagasone-cho, Kita-ku, Sakai, Osaka, 1179-35918025, Japan.
| | - Keisho Chin
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Daisuke Takahari
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Hisashi Hosaka
- Department of Gastroenterology, Gunma Prefectural Cancer Center, Gunma, Japan
| | - Osamu Muto
- Department of Medical Oncology, Japanese Red Cross Akita Hospital, Akita, Japan
| | - Yoshiaki Shindo
- Department of Gastroenterological Surgery, Nakadori General Hospital, Akita, Japan
| | - Naoki Nagata
- Department of Gastroenterological Surgery, Kitakyushu General Hospital, Kitakyushu, Fukuoka, Japan
| | - Hiroshi Yabusaki
- Department of Gastroenterological Surgery, Niigata Cancer Center Hospital, Niigata, Japan
| | - Hiroshi Imamura
- Department of Gastroenterological Surgery, Toyonaka Municipal Hospital, Toyonaka, Osaka, Japan
| | - Shunji Endo
- Department of Gastroenterological Surgery, Yao Municipal Hospital, Yao, Osaka, Japan
| | - Tomomi Kashiwada
- Department of Internal Medicine, Division of Hematology, Respiratory Medicine and Oncology, Faculty of Medicine, Saga University, Saga, Japan
| | - Masato Nakamura
- Aizawa Comprehensive Cancer Center, Aizawa Hospital, Matsumoto, Nagano, Japan
| | - Jun Hihara
- Department of Gastroenterological Surgery, Hiroshima City North Medical Center Asa Citizens Hospital, Hiroshima, Japan
| | - Michiya Kobayashi
- Cancer Treatment Center, Kochi Medical School Hospital, Nankoku, Kochi, Japan
| | - Tamotsu Sagawa
- Department of Gastroenterology, National Hospital Organization Hokkaido Cancer Center, Sapporo, Hokkaido, Japan
| | - Soh Saito
- Department of Gastroenterology, Misawa Citi Hospital, Misawa, Aomori, Japan
| | - Atsushi Sato
- Department of Medical Oncology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Takeshi Yamada
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaragi, Japan
| | - Naohiro Okano
- Department of Medical Oncology, Kyorin University Faculty of Medicine, Mitaka, Tokyo, Japan
| | - Ken Shimada
- Department of Internal Medicine, Division of Medical Oncology, Showa University Koto-Toyosu Hospital, Tokyo, Japan
| | - Masashi Matsushima
- Department of Gastroenterology, Tokai University School of Medicine, Tokyo, Japan
| | - Masato Kataoka
- Department of Surgery, National Hospital Organization Nagoya Medical Center, Tokyo, Japan
| | - Shigemi Matsumoto
- Department of Clinical Oncology, Kyoto University Hospital, Kyoto, Japan
| | - Masahiro Goto
- Cancer Chemotherapy Center, Osaka Medical and Pharmaceutical University Hospital, Suita, Osaka, Japan
| | | | - Takeshi Shiraishi
- Department of Medical Oncology, Japanese Red Cross Matsuyama Hospital, Matsuyama, Ehime, Japan
| | - Hiromichi Yamai
- Department of Gastroenterological Surgery, Japanese Red Cross Kochi Hospital, Kochi, Japan
| | - Fumio Nagashima
- Department of Medical Oncology, Kyorin University Faculty of Medicine, Mitaka, Tokyo, Japan
| | - Naoki Ishizuka
- Clinical Planning and Strategy Department Center for Development of Advanced Cancer Therapy, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Kensei Yamaguchi
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
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Ye Z, Chen J, Rao Y, Yang W. Should S-1 be better than capecitabine for patients with advanced gastric cancer in Asia? A systematic review and meta-analysis. Onco Targets Ther 2018; 12:269-277. [PMID: 30643425 PMCID: PMC6312060 DOI: 10.2147/ott.s187815] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
Background S-1 or capecitabine (Cap) containing treatment is an increasingly used strategy in patients with advanced gastric cancer in Asia. It is unclear whether there is sufficient evidence to support which regimen is better. Methods A systematic review of retrospective studies and randomized controlled trials (RCTs) comparing S-1 with Cap containing treatment in advanced gastric cancer patients was performed. Embase, PubMed, ClinicalTrials.gov, Cochrane Library, and reference lists were searched from inception until August 2018 for relevant studies. Outcomes of interest included 1-year overall survival (OS), 1-year progression-free survival (PFS), objective response rate (ORR), and adverse events. Meta-analyses of the random events were performed. We also performed sensitivity analysis to examine whether the results of the meta-analyses were robust. Results A total of 770 subjects from six RCTs and two retrospective studies in Asia were analyzed. Compared with S-1, Cap containing treatment had better ORR (overall risk ratio =0.85, 95% CI: 0.72, 0.99, I 2=0%, P=0.043) and higher incidence of all-grade hand-foot syndrome (HFS) (overall risk ratio =0.29, 95% CI: 0.20, 0.40, I 2=0%, P<0.001) and neutropenia (overall risk ratio =0.85, 95% CI: 0.73, 0.99, I 2=0%, P=0.039). But there was no statistical difference in 1-year PFS, 1-year OS, incidence of other all-grade or grade 3-4 adverse events between S-1 and Cap containing arms (P>0.05). We found no publication bias in this review. Conclusion This systematic review showed that for Asian patients, Cap shows superiority in ORR but not 1-year OS or PFS, and it will increase the risk of all-grade HFS and neutropenia. Until now, S-1 containing treatment might be a better choice for advanced gastric cancer patients. But more high-quality RCTs are needed to confirm these results.
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Affiliation(s)
- Ziqi Ye
- Department of Pharmacy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Jie Chen
- Department of Pharmacy, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Yuefeng Rao
- Department of Pharmacy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Wenchao Yang
- Department of Pharmacy, Traditional Chinese Medical Hospital of Zhuji, Zhuji, China,
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Kawakami H, Takeno A, Endo S, Makari Y, Kawada J, Taniguchi H, Tamura S, Sugimoto N, Kimura Y, Tamura T, Fujitani K, Sakai D, Shimokawa T, Kurokawa Y, Satoh T. Randomized, Open-Label Phase II Study Comparing Capecitabine-Cisplatin Every 3 Weeks with S-1-Cisplatin Every 5 Weeks in Chemotherapy-Naïve Patients with HER2-Negative Advanced Gastric Cancer: OGSG1105, HERBIS-4A Trial. Oncologist 2018; 23:1411-e147. [PMID: 30115736 PMCID: PMC6292554 DOI: 10.1634/theoncologist.2018-0175] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Accepted: 05/24/2018] [Indexed: 01/23/2023] Open
Abstract
LESSONS LEARNED Evidence has suggested that capecitabine-cisplatin is similar or possibly superior to S-1-cisplatin in terms of safety and efficacy for Japanese patients with advanced gastric cancer (AGC).As far as we are aware, our study is the first randomized trial of two regimens consisting of an oral fluoropyrimidine plus cisplatin in human epidermal growth receptor 2-negative AGC patients with measurable lesions. BACKGROUND We performed a phase II study to evaluate the safety and efficacy of capecitabine plus cisplatin in comparison with S-1 plus cisplatin for first-line treatment of human epidermal growth receptor 2 (HER2)-negative advanced gastric cancer in Japan. METHODS Eligible patients were randomly assigned to receive either capecitabine at 1,000 mg/m2 twice daily for 14 days plus cisplatin at 80 mg/m2 on day 1 every 3 weeks (n = 43) or S-1 at 40-60 mg twice daily for 21 days plus cisplatin at 60 mg/m2 on day 8 every 5 weeks (n = 41). The primary endpoint of the study was response rate. RESULTS Response rate did not differ significantly between the capecitabine-cisplatin and S-1-cisplatin groups (53.5% vs. 51.2%, respectively, p > .999). S-1-cisplatin tended to confer a better progression-free survival (PFS; median of 5.9 vs. 4.1 months, p = .284), overall survival (OS; median of 13.5 vs. 10.0 months, p = .290), and time to treatment failure (TTF; median of 4.5 vs. 3.1 months, p = .052) compared with capecitabine-cisplatin. Common hematologic toxicities of grade 3 or 4 included anemia and neutropenia in both groups. However, anorexia, fatigue, and hyponatremia of grade 3 or 4 occurred more frequently in the capecitabine-cisplatin group. CONCLUSION Capecitabine-cisplatin failed to demonstrate superior efficacy compared with S-1-cisplatin. The higher incidence of severe adverse events with capecitabine-cisplatin suggests that S-1-cisplatin should remain the standard first-line chemotherapy for HER2-negative advanced gastric cancer in Japan.
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Affiliation(s)
- Hisato Kawakami
- Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Atsushi Takeno
- Department of Surgery, Kansai Rosai Hospital, Hyogo, Japan
| | - Shunji Endo
- Department of Surgery, Higashiosaka City Medical Center, Osaka, Japan
| | - Yoichi Makari
- Department of Surgery, Sakai City Medical Center, Osaka, Japan
| | - Junji Kawada
- Department of Surgery, Kaizuka City Hospital, Osaka, Japan
| | | | | | - Naotoshi Sugimoto
- Department of Medical Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Yutaka Kimura
- Department of Surgery, Kindai University Faculty of Medicine, Osaka, Japan
| | - Takao Tamura
- Department of Medical Oncology, Kindai University Nara Hospital, Nara, Japan
| | | | - Daisuke Sakai
- Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Toshio Shimokawa
- Clinical Study Support Center, Wakayama Medical University, Wakayama, Japan
| | - Yukinori Kurokawa
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Taroh Satoh
- Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Osaka, Japan
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Sun J, Ren Z, Sun X, Hou H, Li K, Ge Q. Efficacy and safety comparison of chemotherapies for advanced gastric cancer: A network meta-analysis. Oncotarget 2017; 8:39673-39682. [PMID: 28562333 PMCID: PMC5503642 DOI: 10.18632/oncotarget.17784] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2017] [Accepted: 04/03/2017] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE Chemotherapy is one of the commonly used therapies for advanced gastric cancer. In this study, we performed a network meta-analysis on the efficacy and safety of common treatments to give evidences of their relative benefits. RESULTS 32 trials with 8550 patients and 20 regimens were included in this study. According to the results of primary outcomes, 5-FU plus OXA, 5-FU plus DOC, CAP plus CIS, CAP plus OXA, S-1 plus OXA and S-1 plus PAC performed well in improving OS and ORR. As for the adverse events, S-1 had a safer effect than other treatments, conversely, 5-FU plus CIS ranked the last. However, there was no regimen with outstanding performances in both efficacy and safety. MATERIALS AND METHODS Studies were searched from database and screened with criteria. The Bayesian framework based network meta-analysis was performed with software R and STATA. Overall survival (OS) and overall response rate (ORR) were considered as primary outcomes while adverse events as secondary outcomes. The outcomes were represented by hazard ratios or odd ratios with 95% corresponding credible intervals, respectively. CONCLUSIONS The network meta-analysis suggested that 5-FU plus OXA and 5-FU plus DOC were recommended when efficacy was stressed. S-1 was safest but poorly effective. A regimen, as an excellent combination of efficacy and safety, is still waiting to be discovered.
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Affiliation(s)
- Jinping Sun
- Department of Digestive Internal Medicine, Huaihe Hospital of Henan University, Kaifeng, 475000, Henan, China
| | - Zheng Ren
- Department of Digestive Internal Medicine, Huaihe Hospital of Henan University, Kaifeng, 475000, Henan, China
| | - Xinfang Sun
- Department of Digestive Internal Medicine, Huaihe Hospital of Henan University, Kaifeng, 475000, Henan, China
| | - Hongtao Hou
- Department of Digestive Internal Medicine, Huaihe Hospital of Henan University, Kaifeng, 475000, Henan, China
| | - Ke Li
- Department of Digestive Internal Medicine, Huaihe Hospital of Henan University, Kaifeng, 475000, Henan, China
| | - Quanxing Ge
- Department of Digestive Internal Medicine, Huaihe Hospital of Henan University, Kaifeng, 475000, Henan, China
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Duo-Ji MM, Ci-Ren BS, Long ZW, Zhang XH, Luo DL. Short-term efficacy of different chemotherapy regimens in the treatment of advanced gastric cancer: a network meta-analysis. Oncotarget 2017; 8:37896-37911. [PMID: 28099947 PMCID: PMC5514960 DOI: 10.18632/oncotarget.14664] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2016] [Accepted: 11/14/2016] [Indexed: 01/13/2023] Open
Abstract
OBJECTIVE A network meta-analysis was performed to compare the short-term efficacy of different chemotherapy regimens in the treatment of advanced gastric cancer. METHODS Randomized controlled trials of different chemotherapy regimens for advanced gastric cancer were included in this study. Network meta-analysis combined direct evidence and indirect evidence to evaluate the odds ratio and draw surface under the cumulative ranking curves of different chemotherapy regimens in advanced gastric cancer. RESULTS The results of surface under the cumulative ranking curves showed that S-1 and capecitabine regimens were better than fluorouracil. As for multi-drug combination regimens, the disease control rate of cisplatin + capecitabine, docetaxel + cisplatin + fluorouracil and etoposide + cisplatin + capecitabine regimens were relatively better, while fluorouracil + adriamycin + mitomycin regimen was relatively poorer when compared with cisplatin + fluorouracil regimen. Additionally, the overall response ratio of cisplatin + capecitabine, paclitaxel + fluorouracil, docetaxel + cisplatin + fluorouracil and etoposide + cisplatin + fluorouracil regimens were relatively better, while the disease control rate of fluorouracil + adriamycin + mitomycin regimen was relatively poorer when compared with cisplatin + fluorouracil regimen. Furthermore, the results of cluster analysis demonstrated that cisplatin + capecitabine, etoposide + cisplatin + capecitabine, S-1 + paclitaxel and S-1 + irinotecan chemotherapy regimens had better disease control rate and overall response ratio for advanced gastric cancer patients. CONCLUSION This network meta-analysis clearly showed that multi-drug combination chemotherapy regimens based on capecitabine and S-1 might be the best chemotherapy regimen for advanced gastric cancer.
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Affiliation(s)
- Mi-Ma Duo-Ji
- Department of Medicine, Shigatse People's Hospital, Shigatse 857000, P.R. China
| | - Ba-Sang Ci-Ren
- Department of Medicine, Shigatse People's Hospital, Shigatse 857000, P.R. China
| | - Zi-Wen Long
- Department of Gastric Cancer and Soft-Tissue Sarcoma Sugery, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China
| | - Xiao-Hua Zhang
- Department of Medicine, Shigatse People's Hospital, Shigatse 857000, P.R. China
| | - Dong-Lin Luo
- Department of Medicine, Shigatse People's Hospital, Shigatse 857000, P.R. China
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Zhu B, Wu JR, Zhou XP. A Retrospective Comparison of Trastuzumab Plus Cisplatin and Trastuzumab Plus Capecitabine in Elderly HER2-Positive Advanced Gastric Cancer Patients. Medicine (Baltimore) 2015; 94:e1428. [PMID: 26313797 PMCID: PMC4602910 DOI: 10.1097/md.0000000000001428] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
A combination of trastuzumab and cisplatin or trastuzumab and capecitabine has been confirmed to be effective for treating adverse effects in with HER2-positive advanced gastric cancer (AGC) patients. We retrospectively compared the activity and safety of trastuzumab plus cisplatin (HP) and trastuzumab plus capecitabine (HX) for elderly HER2-positive AGC patients.Ninety two HER2-positive AGC patients were included in this study; of those 48 patients received trastuzumab (course 1, 8 mg/kg followed by course 2, onward, 6 mg/kg on day 1) plus cisplatin (60 mg/m) intravenously on day 1 of a 3-week cycle and 44 patients received trastuzumab (course 1, 8 mg/kg; course 2 onward, 6 mg/kg) plus intravenous oral capecitabine (1000 mg/m twice daily on days 1-14), every 3 weeks. The primary end point was overall survival (OS). The secondary end points included objective response rate (ORR), progression-free survival (PFS), and toxicity.The median age was 71 years in both groups. The median OS was 15.5 months in the HP group and 17.0 months in the HX group, with no significant difference between the 2 groups (P = 0.78). There were also no significant differences in PFS (median 6.6 months vs 7.2 months, respectively; P = 0.90) and ORR (58.3% vs 59.1%, respectively; P = 1.00) between the HP group and the HX group. The major grade 3 or 4 adverse events in the HP group and the HX group were neutropenia (35.4% vs 29.5%, respectively), followed by anorexia (25.0% vs 22.7%, respectively), and anemia (16.7% vs 13.6%, respectively), no significant differences were observed.HP and HX were associated with similar efficacy and safety in HER2-positive AGC patients.
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Affiliation(s)
- Bo Zhu
- From the Department of Clinical Laboratory, The Afffiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, China (BZ, J-RW); and Department of Clinical Laboratory, First Affiliated Hospital of Guangxi University of Chinese Medicine (X-PZ)
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He AB, Peng XL, Song J, Zhang JX, Dong WG, Luo RF, Tang Y. Efficacy of S-1 vs capecitabine for the treatment of gastric cancer: A meta-analysis. World J Gastroenterol 2015; 21:4358-4364. [PMID: 25892887 PMCID: PMC4394098 DOI: 10.3748/wjg.v21.i14.4358] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2014] [Revised: 09/12/2014] [Accepted: 10/21/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To rationally evaluate the effect of S-1 vs capecitabine for the treatment of gastric cancer.
METHODS: MEDLINE, EMBASE, Cochrane Controlled Trials Register, Google Scholar, and China Journal Full Text Database were accessed to collect clinical randomized controlled trials regarding the effect of S-1 vs capecitabine for the treatment of gastric cancer patients. Statistical analysis was performed by meta-analysis. Four randomized controlled trials met the inclusion criteria.
RESULTS: Compared with capecitabine regimens, the 1-year survival rate in gastric cancer patients was 0.80 (95%CI: 0.52-1.21, P = 0.29). The overall response rate of S-1 vs capecitabine was 0.94 (95%CI: 0.59-1.51, P = 0.93). Compared with capecitabine regimens, the most frequent hematologic toxicities were neutropenia (OR = 0.99, 95%CI: 0.65-1.49, P = 0.94) and thrombocytopenia (OR = 0.72, 95%CI: 0.31-1.67, P = 0.44). The most frequent non-hematologic toxicities included nausea (OR = 0.85, 95%CI: 0.56-1.28, P = 0.43) and hand-foot syndrome (OR = 0.16, 95%CI: 0.10-0.27, P < 0.00001).
CONCLUSION: The existing studies suggest that S-1 is not more effective than capecitabine in the treatment of gastric cancer patients, but does exhibit less toxicity with regard to hand-foot syndrome.
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Wu FL, Lu DC, Ying YP, Huang JJ, Zhou AM, Jiang DK, Chen MW, Yang X, Zhou J, Huang HQ, Zeng HY. A Meta-analysis Reveals S-1-based Chemotherapy Improves the Survival of Patients With Advanced Gastric Cancer. Medicine (Baltimore) 2015; 94:e652. [PMID: 25906091 PMCID: PMC4602687 DOI: 10.1097/md.0000000000000652] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
The aim of this study was to compare the efficacy and safety of S-1-based therapy versus non-S-1-based therapy in advanced gastric cancer (AGC) patients.Eligible studies stratifying objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) in AGC patients were identified from Embase, Pubmed, Cochrane Library, and China National Knowledge Infrastructure databases. The STATA package (version 11.0) was used to pool the data from the eligible studies.Fifteen studies with 2973 AGC cases, of which 1497 (50.4%) received S-1-based therapy and 1476 (49.6%) received non-S-1-based therapy, were identified in the meta-analysis. AGC patients who had received S-1-based therapy had a higher median OS, median PFS, and ORR than those who had received 5-fluorouracil (FU)-based therapy (OS: hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.80-0.98, P = 0.015; PFS: HR 0.88, 95% CI 0.80-0.98, P = 0.016; ORR: OR 1.25, 95% CI 1.08-1.45, P = 0.003, respectively). S-1-based therapy had similar efficacy to capecitabine-based therapy in terms of median OS (HR 1.14, 95% CI 0.91-1.41, P = 0.253), median PFS (HR 1.01, 95% CI 0.82-1.25, P = 0.927), and ORR (OR 0.84, 95% CI 0.63-1.12, P = 0.226). Subgroup analysis for grade 3 to 4 toxicity showed higher incidence of neutropenia (relative risk [RR] = 0.827, P = 0.006), nausea (RR = 0.808, P = 0.040), and lower diarrhea (RR = 1.716, P = 0.012) in 5-FU-based arm, and higher diarrhea (RR = 0.386, P = 0.007) in capecitabine-based arm.S-1-based chemotherapy is favorable to AGC patients with better clinical benefit than 5-FU-based chemotherapy and with equivalent antitumor compare with capecitabine-based therapy.
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Affiliation(s)
- Fang-Lan Wu
- From the Hospital Quality Management Office (F-LW); Department of Endocrinology (D-CL, A-MZ, XY, JZ, H-QH); Department of Thoracic and Cardiovascular Surgery (Y-PY); Outpatient Department (J-JH, H-YZ); Department of Gastroenterology (D-KJ); and Department of Infectious Disease, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China (M-WC)
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10
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Kim ST, Hong YS, Lim HY, Lee J, Kim TW, Kim KP, Kim SY, Baek JY, Kim JH, Lee KW, Chung IJ, Cho SH, Lee KH, Shin SJ, Kang HJ, Shin DB, Lee JW, Jo SJ, Park YS. S-1 plus oxaliplatin versus capecitabine plus oxaliplatin for the first-line treatment of patients with metastatic colorectal cancer: updated results from a phase 3 trial. BMC Cancer 2014; 14:883. [PMID: 25424120 PMCID: PMC4289339 DOI: 10.1186/1471-2407-14-883] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2014] [Accepted: 11/18/2014] [Indexed: 02/07/2023] Open
Abstract
Background We report updated progression-free survival (PFS) and overall survival (OS) data from a trial that compared capecitabine plus oxaliplatin (CapeOX) versus S-1 plus oxaliplatin (SOX) for the first-line treatment of metastatic colorectal cancer. Methods This trial was a randomized, two-armed, non-inferiority phase 3 comparison of CapeOX (capecitabine 1000 mg/m2 twice daily on days 1–14 and oxaliplatin 130 mg/m2 on day 1) versus SOX (S-1 40 mg/m2 twice daily on days 1–14 and oxaliplatin 130 mg/m2 on day 1). The primary end point was to show non-inferiority of SOX relative to CapeOX in terms of PFS. Thus, a follow-up exploratory analysis of PFS and OS was performed. Results The intention to treat (ITT) population was comprised of 340 patients (SOX arm: 168 and CapeOX arm: 172). The updated median PFS was 7.1 months (95% CI 6.4-8.0) in the SOX group and 6.3 months (95% CI 4.9-6.7) in the CapeOX group (hazard ratio [HR], 0.83 [0.66-1.04], p = .10). The median OS was 19.0 months (95% CI 15.3-23.0) in the SOX group and 18.4 months (95% CI 14.1-20.7) in the CapeOX group (HR, 0.86 [0.68-1.08], p = .19). Subgroup analyses according to principal demographic factors such as sex, age, ECOG (Eastern Cooperative Oncology Group) performance status, primary tumor location, measurability, previous adjuvant therapy, number of metastatic organs, and liver metastases showed no interaction between any of these characteristics and the treatment. Conclusions Updated survival analysis shows that SOX is similar to CapeOX, confirming the initial PFS analysis. Therefore, the SOX regimen could be an alternative first-line doublet chemotherapy strategy for patients with metastatic colorectal cancer. Trial registration NCT00677443 and May 12 2008
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Young Suk Park
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Korea.
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11
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Zhang X, Cao C, Zhang Q, Chen Y, Gu D, Shen Y, Gong Y, Chen J, Tang C. Comparison of the efficacy and safety of S-1-based and capecitabine-based regimens in gastrointestinal cancer: a meta-analysis. PLoS One 2014; 9:e84230. [PMID: 24392116 PMCID: PMC3879291 DOI: 10.1371/journal.pone.0084230] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2013] [Accepted: 11/21/2013] [Indexed: 12/27/2022] Open
Abstract
PURPOSE Oral fluoropyrimidine (S-1, capecitabine) has been considered as an important part of various regimens. We aimed to evaluate the efficacy and safety of S-1-based therapy versus capecitabine -based therapy in gastrointestinal cancers. METHODS Eligible studies were identified from Pubmed, EMBASE. Additionally, abstracts presented at American Society of Clinical Oncology (ASCO) conferences held between 2000 and 2013 were searched to identify relevant clinical trials. The outcome included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR) and advent events. RESULTS A total of 6 studies (4 RCTs and 2 retrospective analysis studies) containing 790 participants were included in this meta-analysis, including 401 patients in the S-1-based group and 389 patients in the capecitabine-based group. Results of our meta-analysis indicated that S-1-based and capecitabine-based regimens showed very similar efficacy in terms of PFS (HR 0.92, 95% CI 0.78-1.09, P = 0.360), OS (HR 1.01, 95% CI 0.84-1.21, P = 0.949), ORR (HR 1.04, 95% CI 0.87-1.25, P = 0.683) and DCR (HR 1.02, 95% CI 0.94-1.10, P = 0.639). There was also no significant difference in toxicity between regimens other than mild more hand-foot syndrome in capecitabine-based regimens. CONCLUSION Both the S-1-based and capecitabine-based regimens are equally active and well tolerated, and have the potential of backbone chemotherapy regimen in further studies of gastrointestinal cancers.
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Affiliation(s)
- Xunlei Zhang
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Chunxiang Cao
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Qi Zhang
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Yi Chen
- Department of Oncology, Nanjing First Hospital, Medical School of Southeast University, Nanjing, China
| | - Dongying Gu
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Yunzhu Shen
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Yongling Gong
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Jinfei Chen
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Cuiju Tang
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
- * E-mail:
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He MM, Wu WJ, Wang F, Wang ZQ, Zhang DS, Luo HY, Qiu MZ, Wang FH, Ren C, Zeng ZL, Xu RH. S-1-based chemotherapy versus capecitabine-based chemotherapy as first-line treatment for advanced gastric carcinoma: a meta-analysis. PLoS One 2013; 8:e82798. [PMID: 24349363 PMCID: PMC3861463 DOI: 10.1371/journal.pone.0082798] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2013] [Accepted: 10/28/2013] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Although both oral fluoropyrimidines were reported effective and safe, doubts exist about whether S-1 or capecitabine is more advantageous in advanced gastric carcinoma (AGC). Herein, we performed a meta-analysis to comprehensively compare the efficacy and safety of S-1-based chemotherapy versus capecitabine-based chemotherapy as first-line treatment for AGC. METHODS PubMed/Medline, EmBase, Cochrane library, and China National Knowledge Infrastructure databases were searched for articles comparing S-1-based chemotherapy to capecitabine-based chemotherapy for AGC. Primary outcomes were overall response rate (ORR), time to progression (TTP), overall survival (OS), progression-free probability, and survival probability. Secondary outcomes were toxicities. Fixed-effects model were used and all the results were confirmed by random-effects model. RESULTS Five randomized controlled trials and five cohort studies with 821 patients were included. We found equivalent ORR (38.3% vs. 39.1%, odds ratio [OR] 0.92, 95% confidence interval [CI] 0.69-1.24, P = 0.59), TTP (harzad ratio [HR] 0.98, 95% CI 0.82-1.16, P = 0.79), OS (HR 0.99, 95% CI 0.87-1.13, P = 0.91), progression-free probability (3-month OR 1.02, 95% CI 0.62-1.68, P = 0.94; 6-month OR 1.34, 95% CI 0.88-2.04, P = 0.18) and survival probability (0.5-year OR 0.90, 95% CI 0.61-1.31, P =0.57; 1-year OR 0.97, 95% CI 0.70- 1.33, P = 0.84; 2-year OR 1.15, 95% CI 0.61-2.17, P = 0.66). Equivalent grade 3 to 4 hematological and non-hematological toxicities were found except hand-foot syndrome was less prominent in S-1-based chemotherapy (0.3% vs. 5.9%, OR 0.19, 95% CI 0.06-0.56, P = 0.003). There're no significant heterogeneity and publication bias. Cumulative analysis found stable time-dependent trend. Consistent results stratified by study design, age, regimen, cycle, country were observed. CONCLUSION S-1-based chemotherapy was associated with non-inferior antitumor efficacy and better safety profile, compared with capecitabine-based therapy. We recommended S-1 and capecitabine can be used interchangeably for AGC, at least in Asia.
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Affiliation(s)
- Ming-ming He
- Department of Medical Oncology and State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Wen-jing Wu
- Department of Medical Oncology and State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Feng Wang
- Department of Medical Oncology and State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Zhi-qiang Wang
- Department of Medical Oncology and State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Dong-sheng Zhang
- Department of Medical Oncology and State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Hui-yan Luo
- Department of Medical Oncology and State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Miao-zhen Qiu
- Department of Medical Oncology and State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Feng-hua Wang
- Department of Medical Oncology and State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Chao Ren
- Department of Medical Oncology and State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Zhao-lei Zeng
- Department of Medical Oncology and State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Rui-hua Xu
- Department of Medical Oncology and State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
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