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Luksta M, Bausys A, Bickaite K, Rackauskas R, Paskonis M, Luksaite-Lukste R, Ranceva A, Stulpinas R, Brasiuniene B, Baltruskeviciene E, Lachej N, Sabaliauskaite R, Bausys R, Tulyte S, Strupas K. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) with cisplatin and doxorubicin in combination with FOLFOX chemotherapy as a first-line treatment for gastric cancer patients with peritoneal metastases: single-arm phase II study. BMC Cancer 2023; 23:1032. [PMID: 37875869 PMCID: PMC10599063 DOI: 10.1186/s12885-023-11549-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2023] [Accepted: 10/19/2023] [Indexed: 10/26/2023] Open
Abstract
BACKGROUND Gastric cancer (GC) remains among the most common and most lethal cancers worldwide. Peritoneum is the most common site for distant dissemination. Standard treatment for GC peritoneal metastases (PM) is a systemic therapy, but treatment outcomes remain very poor, with median overall survival ranging between 3-9 months. Thus, novel treatment methods are necessary. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is the most novel technique for intraperitoneal chemotherapy. Some preliminary data suggest PIPAC can achieve improved long-term outcomes in patients with GC PM, especially when used in combination with systemic chemotherapy. However, there is a lack of data from well-design prospective studies that would confirm the efficacy of PIPAC and systemic therapy combination for first-line treatment. METHODS This study is an investigator-initiated single-arm, phase II trial to investigate the efficacy of PIPAC combined with systemic FOLFOX (5-fluorouracil, oxaliplatin, leucovorin) as a first-line treatment for GC PM. The study is conducted in 2 specialized GC treatment centers in Lithuania. It enrolls GC patients with histologically confirmed PM without prior treatment. The treatment protocol consists of PIPAC with cisplatin (10.5 mg/m2 body surface in 150 mL NaCl 0.9%) and doxorubicin (2.1 mg/m2 in 50 mL NaCl 0.9%) followed by 2 cycles of FOLFOX every 6-7 weeks. In total 3 PIPACs and 6 cycles of FOLFOX will be utilized. The primary outcome of the study is the objective response rate (ORR) according to RECIST v. 1.1 criteria (Eisenhauer et al., Eur J Cancer 45:228-47) in a CT scan performed 7 days after the 4th cycle of FOLFOX. Secondary outcomes include ORR after all experimental treatment, PIPAC characteristics, postoperative morbidity, histological and biochemical response, ascites volume, quality of life, overall survival, and toxicity. DISCUSSION This study aims to assess PIPAC and FOLFOX combination efficacy for previously untreated GC patients with PM. TRIAL REGISTRATION NCT05644249. Registered on December 9, 2022.
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Affiliation(s)
- Martynas Luksta
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania, Ciurlionio str. 21, 03101.
| | - Augustinas Bausys
- Department of Abdominal Surgery and Oncology, National Cancer Institute, Vilnius, Lithuania
- Centre for Visceral Medicine and Translational Research, Faculty of Medicine, Institute of Clinical Medicine, Vilnius University, Vilnius, 03101, Lithuania
| | - Klaudija Bickaite
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania, Ciurlionio str. 21, 03101
| | - Rokas Rackauskas
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania, Ciurlionio str. 21, 03101
| | - Marius Paskonis
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania, Ciurlionio str. 21, 03101
| | - Raminta Luksaite-Lukste
- Department of Radiology, Nuclear Medicine and Medical Physics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
| | - Anastasija Ranceva
- Hematology, Oncology, and Transfusion Medicine Center, Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania
| | - Rokas Stulpinas
- National Center of Pathology, Affiliate of Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania
| | - Birute Brasiuniene
- Department of Medical Oncology, National Cancer Institute, Vilnius, Lithuania
- Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
| | | | - Nadezda Lachej
- Department of Medical Oncology, National Cancer Institute, Vilnius, Lithuania
| | - Rasa Sabaliauskaite
- Laboratory of Genetic Diagnostic, National Cancer Institute, Santariškių 1, Vilnius, LT-08406, Lithuania
| | - Rimantas Bausys
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania, Ciurlionio str. 21, 03101
- Department of Abdominal Surgery and Oncology, National Cancer Institute, Vilnius, Lithuania
| | - Skaiste Tulyte
- Hematology, Oncology, and Transfusion Medicine Center, Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania
- Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
| | - Kestutis Strupas
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania, Ciurlionio str. 21, 03101
- Centre for Visceral Medicine and Translational Research, Faculty of Medicine, Institute of Clinical Medicine, Vilnius University, Vilnius, 03101, Lithuania
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Qiang W, Shi H, Wu J, Ji M, Wu C. Hepatic Arterial Infusion Combined with Systemic Chemotherapy for Patients with Extensive Liver Metastases from Gastric Cancer. Cancer Manag Res 2020; 12:2911-2916. [PMID: 32425604 PMCID: PMC7196811 DOI: 10.2147/cmar.s245697] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2020] [Accepted: 03/31/2020] [Indexed: 12/27/2022] Open
Abstract
Purpose Liver metastases in patients with gastric cancer often indicate poor prognosis. Once liver metastases are extensive, it is difficult to achieve disease control by using systemic chemotherapy alone. The purpose of this study was to evaluate the effect and safety of hepatic arterial infusion (HAI) combined with systemic chemotherapy on extensive liver metastases from gastric cancer. Patients and Methods Between 2012 and 2019, 21 patients with extensive liver metastases from gastric cancer (LMGC) were enrolled in our study. Liver metastases were identified as unresectable and a major factor affecting prognosis mainly based on size and number of intrahepatic lesions. All patients received systemic chemotherapy with S-1 and HAI oxaliplatin plus floxuridine (FUDR). Results Liver metastases in 16 patients (76.2%) were evaluated as H3. The overall response rate was 76.2% (9.5% complete response). Intrahepatic and extrahepatic median progression-free survival times were 9.5 and 5.2 months, respectively. Median survival time (MST) was 12.3 months. All patients did not have the toxicity of grade 4. Grade 3 toxic effects included bone marrow suppression (14.3%) and diarrhea (9.5%). The other treatment-related toxicities were mild and reversible. Conclusion HAI combined with systemic chemotherapy for extensive LMGC seems to be safe and effective, which achieves a high-local response and may contribute to long survival time for patients.
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Affiliation(s)
- Weiguang Qiang
- Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, People's Republic of China
| | - Hongbing Shi
- Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, People's Republic of China
| | - Jun Wu
- Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, People's Republic of China
| | - Mei Ji
- Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, People's Republic of China
| | - Changping Wu
- Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, People's Republic of China.,Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, People's Republic of China
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Fiorillo C, Laterza V, Quero G, Menghi R, Cina C, Rosa F, Tortorelli AP, Boskoski I, Alfieri S. From biology to surgery: One step beyond histology for tailored surgical treatments of gastric cancer. Surg Oncol 2020; 34:86-95. [PMID: 32891359 DOI: 10.1016/j.suronc.2020.04.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Revised: 03/06/2020] [Accepted: 04/02/2020] [Indexed: 02/07/2023]
Abstract
Gastric cancer is the third most common cause of cancer related death. Although its incidence is globally declined, prognosis remains dismal in the Western hemisphere, while better outcomes are evidenced in Asian countries. Endoscopic or surgical resection with or without lymphadenectomy represents the only chance of cure, with limited improvements of the prognosis in case of associated chemotherapy in a neoadjuvant or adjuvant setting. This could be mainly attributed to the uniform fashion of treatment of gastric cancer, mainly based on the histological features, that usually do not reflect the complexity of the disease. With the recent introduction of genomic technologies and new generation sequencing techniques, gastric cancer biology is now investigated in great details. This has brought to the publication of three main molecular classifications, based on the underlying molecular biology of gastric cancer. Although only few clinical reports are currently present in literature, the identification of gastric cancer molecular subtypes has shown interesting findings that may pave the way to a tailored clinical and surgical management. The aim of this review is, thus, to give a comprehensive overview of the current molecular classifications as compared to the available histopathological ones, also focusing on the potential clinical and surgical benefits and the future perspectives for a more personalized treatment of gastric cancer.
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Affiliation(s)
- Claudio Fiorillo
- Digestive Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy
| | - Vito Laterza
- Digestive Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy
| | - Giuseppe Quero
- Digestive Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy; Università Cattolica del Sacro Cuore di Roma, Italy.
| | - Roberta Menghi
- Digestive Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy
| | - Caterina Cina
- Digestive Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy
| | - Fausto Rosa
- Digestive Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy
| | - Antonio Pio Tortorelli
- Digestive Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy
| | - Ivo Boskoski
- Endoscopy Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy
| | - Sergio Alfieri
- Digestive Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy; Università Cattolica del Sacro Cuore di Roma, Italy
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Macrì A, Morabito F. The use of intraperitoneal chemotherapy for gastric malignancies. Expert Rev Anticancer Ther 2019; 19:879-888. [PMID: 31544548 DOI: 10.1080/14737140.2019.1671189] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Accepted: 09/19/2019] [Indexed: 12/12/2022]
Abstract
Introduction: Gastric cancer is the fourth/fifth most common malignancy worldwide, with only a quarter of patients achieving a 5-year survival rate. It has been estimated that 15-50% or more of patients have peritoneal disease upon surgical exploration. Until the early 1990s, peritoneal metastasis was considered as terminal stage of the disease; in the late 1990s, selected patients with peritoneal metastasis were recategorized as local disease. Over the past two decades, the treatment of peritoneal involvement has transformed, and cytoreductive surgery plus intraperitoneal therapy have drastically altered the natural course of several malignancies. Areas covered: We performed a review of studies available on PubMed from 1 January 2014 to 31 July 2019 and the analysis of their reference citations. We describe the most current intraperitoneal chemotherapy opportunities in the treatment of gastric cancer: hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC), laparoscopic hyperthermic intraperitoneal chemotherapy (LHIPEC), neoadjuvant intraperitoneal and systemic chemotherapy (NIPS), LHIPEC + NIPS, extensive intraoperative peritoneal lavage (EIPL), early postoperative intraperitoneal chemotherapy (EPIC), and pressurized intraperitoneal aerosol chemotherapy (PIPAC). Expert opinion: Comprehensive treatment consisting of CRS combined with perioperative intraperitoneal/systemic chemotherapy can, today, be considered an effective strategy to improve the long-term survival of gastric cancer patients with peritoneal metastasis.
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Affiliation(s)
- Antonio Macrì
- Peritoneal Surface Malignancy and Soft Tissue Sarcoma Program, Messina University Medical School Hospital , Messina , Italy
| | - Federico Morabito
- Peritoneal Surface Malignancy and Soft Tissue Sarcoma Program, Messina University Medical School Hospital , Messina , Italy
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Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with gastric cancer and peritoneal carcinomatosis. Eur J Surg Oncol 2018; 44:1805-1810. [PMID: 30087071 DOI: 10.1016/j.ejso.2018.06.036] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2018] [Revised: 05/23/2018] [Accepted: 06/27/2018] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Gastric Cancer (GC) with Peritoneal Carcinomatosis (PC) has long been regarded as a terminal disease. Over the past two decades, cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has changed the traditional concept of peritoneal metastases from being a systemic disease, to being considered a locoregional dissemination. PATIENTS AND METHODS A prospective study was performed at a high-volume Carcinomatosis Center to evaluate survival, morbi-mortality and prognostic factors for survival in a cohort of patients with GC and PC treated with CRS + HIPEC between June 2006 and December 2016. RESULTS Thirty-five patients were included in the study. Median follow-up was 54 months. Postoperative major complications (>grade IIIa) occurred in 25.7% of patients, including 2 deaths (mortality 5.7%). The median overall survival (OS) was 16 months and the 1-, 3- and 5-year OS rates were 70.8%, 21.3% and 21.3% %, respectively. The median OS for patients with PCI ≤6 was 19 months, in contrast to 12 months for the 19 patients with PCI >6. Three patients were included with only a positive cytology and their median OS was not reached. Perineural invasion was the only factor that had a negative influence in prognosis (HR 18.8) in multivariate analysis. CONCLUSION Although GC with PC still has a poor prognosis, survival has improved in selected patients with CRS + HIPEC and perioperative systemic chemotherapy. Patients with isolated positive cytology or peritoneal carcinomatosis with PCI less than 6 had encouraging survival rates.
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Beeharry MK, Liu WT, Yao XX, Yan M, Zhu ZG. A critical analysis of the cytoreductive surgery with hyperthermic intraperitoneal chemotherapy combo in the clinical management of advanced gastric cancer: an effective multimodality approach with scope for improvement. Transl Gastroenterol Hepatol 2016; 1:77. [PMID: 28138643 DOI: 10.21037/tgh.2016.08.05] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2016] [Accepted: 08/22/2016] [Indexed: 12/16/2022] Open
Abstract
Peritoneal carcinomatosis (PC) is manifested in up to 40% of gastric cancer (GC) patients, after which their 5-year survival drops to less than 5%. The currently most acceptable treatment option for advanced GC (AGC) is systemic chemo and radio therapies with however generally very unsatisfying results and this led to a resurgence of interest in regional therapies like cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Small trials have indicated an association with prolonged survival when applying this technique to AGC manifesting with PC. High procedure-related morbidity and mortality associated with the CRS-HIPEC approach have however brought by a polemic on the merits of the latter: with the advent of regulatory approval of more effective as well as novel, more personalized treatment options in AGC, along with advances in tailoring investigational agents specifically for peritoneal delivery, there clearly is a need to outline the appropriate role of CRS-HIPEC in this disease. In a clear objective to improve the therapeutic efficiency of HIPEC, there have been immense developments in the technical aspects of this technology including the use of nanotechnology in more precise drug delivery systems (DDS) or choice of more efficient drugs such as gene-target technology, laparoscopy and so on. Henceforth, in this review, we will be highlighting the past and current status of the CRS + HIPEC procedure, shedding light on the pros and cons in order to boost up the efficiency of this multimodality approach.
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Affiliation(s)
- Maneesh K Beeharry
- Department of Surgery, Rui Jin Hospital, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Wen-Tao Liu
- Department of Surgery, Rui Jin Hospital, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Xue-Xin Yao
- Department of Surgery, Rui Jin Hospital, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Min Yan
- Department of Surgery, Rui Jin Hospital, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Zheng-Gang Zhu
- Department of Surgery, Rui Jin Hospital, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
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Chia CS, Seshadri RA, Kepenekian V, Vaudoyer D, Passot G, Glehen O. Survival outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis from gastric cancer: a systematic review. Pleura Peritoneum 2016; 1:67-77. [PMID: 30911610 PMCID: PMC6386497 DOI: 10.1515/pp-2016-0010] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2016] [Accepted: 05/08/2016] [Indexed: 02/07/2023] Open
Abstract
Background: The current treatment of choice for peritoneal carcinomatosis from gastric cancer is systemic chemotherapy. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a new aggressive form of loco-regional treatment that is currently being used in pseudomyxoma peritoneii, peritoneal mesothelioma and peritoneal carcinomatosis from colorectal cancer. It is still under investigation for its use in gastric cancer. Methods: The literature between 1970 and 2016 was surveyed systematically through a review of published studies on the treatment outcomes of CRS and HIPEC for peritoneal carcinomatosis from gastric cancer. Results: Seventeen studies were included in this review. The median survival for all patients ranged from 6.6 to 15.8 months. The 5-years overall survival ranged from 6 to 31%. For patients with complete cytoreduction, the median survival was 11.2 to 43.4 months and the 5-years overall survival was 13 % to 23%. Important prognostic factors were found to be a low peritoneal carcarcinomatosis index (PCI) score and the completeness of cytoreduction. Conclusion: The current evidence suggests that CRS and HIPEC has a role to play in the treatment of peritoneal carcinomatosis from gastric cancer. Long term survival has been shown for a select group of patients. However, further studies are needed to validate these results.
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Seshadri RA, Glehen O. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in gastric cancer. World J Gastroenterol 2016; 22:1114-30. [PMID: 26811651 PMCID: PMC4716024 DOI: 10.3748/wjg.v22.i3.1114] [Citation(s) in RCA: 67] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 09/22/2015] [Accepted: 11/30/2015] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer associated peritoneal carcinomatosis (GCPC) has a poor prognosis with a median survival of less than one year. Systemic chemotherapy including targeted agents has not been found to significantly increase the survival in GCPC. Since recurrent gastric cancer remains confined to the abdominal cavity in many patients, regional therapies like aggressive cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been investigated for GCPC. HIPEC has been used for three indications in GC- as an adjuvant therapy after a curative surgery, HIPEC has been shown to improve survival and reduce peritoneal recurrences in many randomised trials in Asian countries; as a definitive treatment in established PC, HIPEC along with CRS is the only therapeutic modality that has resulted in long-term survival in select groups of patients; as a palliative treatment in advanced PC with intractable ascites, HIPEC has been shown to control ascites and reduce the need for frequent paracentesis. While the results of randomised trials of adjuvant HIPEC from western centres are awaited, the role of HIPEC in the treatment of GCPC is still evolving and needs larger studies before it is accepted as a standard of care.
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Coccolini F, Catena F, Glehen O, Yonemura Y, Sugarbaker PH, Piso P, Montori G, Ansaloni L. Complete versus incomplete cytoreduction in peritoneal carcinosis from gastric cancer, with consideration to PCI cut-off. Systematic review and meta-analysis. Eur J Surg Oncol 2015; 41:911-9. [PMID: 25936764 DOI: 10.1016/j.ejso.2015.03.231] [Citation(s) in RCA: 76] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2015] [Revised: 03/19/2015] [Accepted: 03/20/2015] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION The completeness of cytoreduction has been considerated as fundamental in increasing the life expectancy in patients with peritoneal carcinosis (PC) in gastric cancer. However no definitive data about the real effect of complete cytoreduction (CC) have still been published. Moreover the PCI cut-off to attempt CC with a reasonable risk-benefit ratio still lacks. MATERIAL AND METHODS A systematic review with meta-analysis of trials of complete vs incomplete cytoreduction in patients with peritoneal carcinosis from GC was performed. RESULTS Nine trials have been included (748 patients: 417 with CC0-CC1 and 324 with CC2-CC3 cytoreduction). 1, 2, 3 and 5 years survival is favorable to CC0-CC1 (Risk Ratio: 2.41, 8.18, 8.66, and 7.96 respectively). CC0 vs. CC1 survival benefit at 1 and 3 years: RR 2.28 and 6.36 respectively, favoring CC0. 1, 2, 3 and 5 years survival changes significantly above and below a PCI of 12. CONCLUSIONS 1, 2, 3 and 5-year overall survival is increased by CC0-CC1 cytoreduction in patients with PC from gastric origin. Moreover CC0 increases the 1 and 3 years survival when compared to CC1 cytoreduction.
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Affiliation(s)
- F Coccolini
- General Surgery Dept., Papa Giovanni XXIII Hospital, Bergamo, Italy.
| | - F Catena
- General Surgery Dept., Ospedale Maggiore, Parma, Italy
| | - O Glehen
- General Surgery Dept., Centre Hospitalier Lyon Sud, Hospices Civils de Lyon and EMR 3738, Université Lyon 1, France
| | - Y Yonemura
- General Surgery Dept., Kusatsu General Hospital, Yabase 1660, Japan
| | | | - P Piso
- Surgery Dept., University of Regensburg, Regensburg D-93053, Germany
| | - G Montori
- General Surgery Dept., Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - L Ansaloni
- General Surgery Dept., Papa Giovanni XXIII Hospital, Bergamo, Italy
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Magge D, Zenati M, Mavanur A, Winer J, Ramalingam L, Jones H, Zureikat A, Holtzman M, Lee K, Ahrendt S, Pingpank J, Zeh HJ, Bartlett DL, Choudry HA. Aggressive locoregional surgical therapy for gastric peritoneal carcinomatosis. Ann Surg Oncol 2013; 21:1448-55. [PMID: 24197761 DOI: 10.1245/s10434-013-3327-5] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2013] [Indexed: 12/13/2022]
Abstract
BACKGROUND Peritoneal carcinomatosis from gastric cancer (GPC) responds poorly to systemic chemotherapy. Limited published data demonstrate improved outcomes after aggressive locoregional therapies. We assessed the efficacy of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) in GPC. METHODS We prospectively analyzed 23 patients with GPC undergoing CRS/HIPEC between 2001 and 2010. Kaplan-Meier survival curves and multivariate Cox regression models identified prognostic factors affecting oncologic outcomes. RESULTS CRS/HIPEC was performed for synchronous GPC in 20 patients and metachronous GPC in 3 patients. Adequate CRS was achieved in 22 patients (CC-0 = 17; CC-1 = 5) and median peritoneal cancer index was 10.5. Most patients received preoperative chemotherapy (83 %) and total gastrectomy (78 %). Pathology revealed diffuse histology (65 %), signet cells (65 %) and LN involvement (64 %). Major postoperative morbidity occurred in 12 patients, with 1 in-hospital mortality at postoperative day 66. With median follow-up of 52 months, median overall survival (OS) was 9.5 months (95 % confidence interval 4.7-17.3), with 1- and 3- year OS rates of 50 and 18 %. Median progression-free survival (PFS) was 6.8 months (95 % confidence interval 3.9-14.6). In a multivariate Cox regression model, male gender [hazard ratio (HR) 6.3], LN involvement (HR 1.2), residual tumor nodules (HR 2.4), and >2 anastomoses (HR 2.8) were joint significant predictors of poor OS (χ (2) = 18.2, p = 0.001), while signet cells (HR 8.9), anastomoses >2 (HR 5.5), and male gender (HR 2.4) were joint significant predictors of poor progression (χ (2) = 16.3, p = 0.001). CONCLUSIONS Aggressive CRS/HIPEC for GPC may confer a survival benefit in select patients with limited lymph node involvement and completely resectable disease requiring less extensive visceral resections.
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Affiliation(s)
- Deepa Magge
- Division of Surgical Oncology, University of Pittsburgh, Pittsburgh, PA, USA
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Coccolini F, Gheza F, Lotti M, Virzì S, Iusco D, Ghermandi C, Melotti R, Baiocchi G, Giulini SM, Ansaloni L, Catena F. Peritoneal carcinomatosis. World J Gastroenterol 2013; 19:6979-6994. [PMID: 24222942 PMCID: PMC3819534 DOI: 10.3748/wjg.v19.i41.6979] [Citation(s) in RCA: 233] [Impact Index Per Article: 19.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2013] [Revised: 09/12/2013] [Accepted: 09/16/2013] [Indexed: 02/06/2023] Open
Abstract
Several gastrointestinal and gynecological malignancies have the potential to disseminate and grow in the peritoneal cavity. The occurrence of peritoneal carcinomatosis (PC) has been shown to significantly decrease overall survival in patients with liver and/or extraperitoneal metastases from gastrointestinal cancer. During the last three decades, the understanding of the biology and pathways of dissemination of tumors with intraperitoneal spread, and the understanding of the protective function of the peritoneal barrier against tumoral seeding, has prompted the concept that PC is a loco-regional disease: in absence of other systemic metastases, multimodal approaches combining aggressive cytoreductive surgery, intraperitoneal hyperthermic chemotherapy and systemic chemotherapy have been proposed and are actually considered promising methods to improve loco-regional control of the disease, and ultimately to increase survival. The aim of this review article is to present the evidence on treatment of PC in different tumors, in order to provide patients with a proper surgical and multidisciplinary treatment focused on optimal control of their locoregional disease.
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Coccolini F, Cotte E, Glehen O, Lotti M, Poiasina E, Catena F, Yonemura Y, Ansaloni L. Intraperitoneal chemotherapy in advanced gastric cancer. Meta-analysis of randomized trials. Eur J Surg Oncol 2013; 40:12-26. [PMID: 24290371 DOI: 10.1016/j.ejso.2013.10.019] [Citation(s) in RCA: 179] [Impact Index Per Article: 14.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2013] [Revised: 10/20/2013] [Accepted: 10/23/2013] [Indexed: 12/15/2022] Open
Abstract
INTRODUCTION An important component of treatment failure in gastric cancer (GC) is cancer dissemination within the peritoneal cavity and nodal metastasis. Intraperitoneal chemotherapy (IPC) is considered to give a fundamental contribute in treating advanced GC. The purpose of the study is to investigate the effects of IPC in patients with advanced GC. MATERIAL AND METHODS A systematic review with meta-analysis of randomized controlled trials (RCTs) of IPC + surgery vs. control in patients with advanced GC was performed. RESULTS Twenty prospective RCTs have been included (2145 patients: 1152 into surgery + IPC arm and 993 into control arm). Surgery + IPC improves: 1, 2 and 3-year mortality (OR = 0.31, 0.27, 0.29 respectively), 2 and 3-year mortality in patients with loco-regional nodal metastasis (OR = 0.28, 0.16 respectively), 1 and 2-year mortality rate in patients with serosal infiltration (OR = 0.33, 0.27 respectively). Morbidity rate was increased by surgery + IPC (OR = 1.82). The overall recurrence and the peritoneal recurrence rates were improved by surgery + IPC (OR = 0.46 and 0.47 respectively). There was no statistically significant difference in lymph-nodal recurrence rate. The rate of haematogenous metastasis was improved by surgery + IPC (OR = 0.63). CONCLUSIONS 1, 2 and 3-year overall survival is incremented by the IPC. No differences have been found at 5-year in overall survival rate. 2 and 3-year mortality rates in patients with nodal invasion and 1 and 2-year mortality rates in patients with serosal infiltration are improved by the use of IPC. IPC has positive effect on peritoneal recurrence and distant metastasis. Morbidity rate is incremented by IPC. Loco-regional lymph-nodes invasion in patients affected by advanced gastric cancer is not a contraindication to IPC.
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Affiliation(s)
- F Coccolini
- General Surgery Dept., Papa Giovanni XXIII Hospital, Bergamo, Italy; General Surgery Dept., Centre Hospitalier Lyon Sud, Hospices Civils de Lyon and EMR 3738, Université Lyon 1, France.
| | - E Cotte
- General Surgery Dept., Centre Hospitalier Lyon Sud, Hospices Civils de Lyon and EMR 3738, Université Lyon 1, France
| | - O Glehen
- General Surgery Dept., Centre Hospitalier Lyon Sud, Hospices Civils de Lyon and EMR 3738, Université Lyon 1, France
| | - M Lotti
- General Surgery Dept., Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - E Poiasina
- General Surgery Dept., Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - F Catena
- General Surgery Dept., Ospedale Maggiore, Parma, Italy
| | - Y Yonemura
- General Surgery Dept., Kusatsu General Hospital, Yabase 1660, Japan
| | - L Ansaloni
- General Surgery Dept., Papa Giovanni XXIII Hospital, Bergamo, Italy
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Hong SH, Shin YR, Roh SY, Jeon EK, Song KY, Park CH, Jeon HM, Hong YS. Treatment outcomes of systemic chemotherapy for peritoneal carcinomatosis arising from gastric cancer with no measurable disease: retrospective analysis from a single center. Gastric Cancer 2013; 16:290-300. [PMID: 22898806 DOI: 10.1007/s10120-012-0182-1] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2012] [Accepted: 07/07/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND Few studies of systemic chemotherapy have focused on gastric cancer with peritoneal carcinomatosis (PC) without measurable lesions. In the present study, we characterized the outcomes of systemic chemotherapy and prognostic factors for gastric cancer with PC, particularly in patients without measurable disease. METHODS Clinical data from 211 gastric cancer patients with PC (137 without and 74 with measurable disease) who had received systemic chemotherapy between January 2003 and December 2010 at a single center were reviewed. RESULTS The median overall survival (OS) rate of gastric cancer patients with PC with no measurable disease was significantly longer than that of patients with measurable disease (18.0 vs. 11.6 months, p = 0.010). On multivariate analysis, poor performance status [hazard ratio (HR) = 2.15, p < 0.001], the presence of metastatic lymphadenopathy (HR = 2.17, p < 0.001), and high-grade PC (HR = 1.83, p = 0.001) were associated with significantly decreased OS. When patients with low-grade PC were stratified by clinical PC grade, the median OS of those without measurable disease was 19.6 months. The median OS of patients with low-grade PC with no measurable disease was longer than those of patients with high-grade PC without measurable disease, patients with low-grade PC with measurable disease, and patients with high-grade PC with measurable disease (p = 0.001, p = 0.029, and p < 0.001, respectively). Among the patients with low-grade PC, patients who received a gastrectomy had longer survival than patients who did not receive a gastrectomy (p < 0.001). CONCLUSIONS In our study, clinically low-grade PC without measurable disease was associated with better outcomes of systemic chemotherapy than the outcomes in the other groups examined. Clinical trials in patients with gastric cancer with PC should be stratified according to PC grade.
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Affiliation(s)
- Sook Hee Hong
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 505 Banpo-Dong, Seocho-Gu, Seoul, 137-701, South Korea
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14
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Yonemura Y, Elnemr A, Endou Y, Ishibashi H, Mizumoto A, Miura M, Li Y. Effects of neoadjuvant intraperitoneal/systemic chemotherapy (bidirectional chemotherapy) for the treatment of patients with peritoneal metastasis from gastric cancer. Int J Surg Oncol 2012; 2012:148420. [PMID: 22900159 PMCID: PMC3415092 DOI: 10.1155/2012/148420] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2012] [Accepted: 04/29/2012] [Indexed: 12/24/2022] Open
Abstract
Novel multidisciplinary treatment combined with neoadjuvant intraperitoneal-systemic chemotherapy protocol (NIPS) and peritonectomy was developed. Ninety-six patients were enrolled. Peritoneal wash cytology was performed before and after NIPS through a port system. Patients were treated with 60 mg/m(2) of oral S-1 for 21 days, followed by a 1-week rest. On days 1, 8, and 15, 30 mg/m(2) of Taxotere and 30 mg/m(2) of cisplatin with 500 mL of saline were introduced through the port. NIPS is done 2 cycles before surgery. Three weeks after NIPS, 82 patients were eligible to intend cytoreductive surgery (CRS) by gastrectomy + D2 dissection + periotnectomy to achieve complete cytoreduction. Sixty-eight patients showed positice cytology before NIPS, and the positive cytology results became negative in 47 (69%) patients after NIPS. Complete pathologic response on PC after NIPS was experienced in 30 (36.8%) patients. Stage migration was experienced in 12 patients (14.6%). Complete cytoreduction was achieved in 58 patients (70.7%). By the multivariate analysis, complete cytoreduction and pathologic response became a significantly good survival. However the high morbidity and mortality, stringent patient selection is important. The best indications of the therapy are patients with good pathologic response and PCI ≤ 6, which are supposed to be removed completely by peritonectomy.
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Affiliation(s)
- Yutaka Yonemura
- NPO Organization to Support Peritoneal Surface Malignancy Treatment, Osaka, Kishiwada 596-0032, Japan
- Department of Surgery, Kusatsu General Hospital, Shiga, Kusatsu 525-8585, Japan
- Department of Surgery, Peritoneal Surface Malignancy Center, Kishiwada Tokushukai Hospital, Kishiwada 596-8522, Japan
- Peritoneal Dissemination Program, Kishiwada Tokushukai Hospital and Kusatsu General Hospital, NPO Organization to Support Peritoneal Surface Malignancy Treatment, 1-26, Haruki-Moto-Machi, Osaka, Kishiwada City, 596-0032, Japan
| | - Ayman Elnemr
- NPO Organization to Support Peritoneal Surface Malignancy Treatment, Osaka, Kishiwada 596-0032, Japan
- Department of Surgery, Tanta University Hospital, Tanta, Egypt
| | - Yoshio Endou
- Department of Experimental Therapeutics, Cancer Research Institute, Kanazawa University, Kanazawa 920-1192, Japan
| | - Haruaki Ishibashi
- NPO Organization to Support Peritoneal Surface Malignancy Treatment, Osaka, Kishiwada 596-0032, Japan
- Department of Surgery, Peritoneal Surface Malignancy Center, Kishiwada Tokushukai Hospital, Kishiwada 596-8522, Japan
| | - Akiyoshi Mizumoto
- Department of Surgery, Kusatsu General Hospital, Shiga, Kusatsu 525-8585, Japan
| | - Masahiro Miura
- Department of Anatomy, School of Medicine, Oita University, Oita 870-1192, Japan
| | - Yan Li
- Department of Oncology, Zhongnan Hospital, Cancer Center of Wuhan University, Wuhan 430072, China
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15
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Pathological complete response of locally advanced gastric cancer after four courses of neoadjuvant chemotherapy with paclitaxel plus cisplatin: report of a case. Surg Today 2012; 42:983-7. [PMID: 22398719 DOI: 10.1007/s00595-012-0155-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2011] [Accepted: 08/03/2011] [Indexed: 12/29/2022]
Abstract
We report a case of advanced gastric carcinoma treated successfully by four courses of neoadjuvant chemotherapy (NAC) with paclitaxel and cisplatin. The patient was a 43-year-old man with advanced gastric cancer, clinically diagnosed as P0H0M0CY0T3N2, which had invaded the upper body of the stomach and esophagus. He was entered into a clinical trial and received the following NAC regimen: paclitaxel 80 mg/m(2), and cisplatin 25 mg/m(2), on days 1, 8, and 15, followed by a rest on day 22, as one course. The lymph nodes had reduced in size to 59% after two courses and to 40% after four courses, with no sign of severe toxicity. Subsequently, he underwent D2 total gastrectomy with pancreatico-splenectomy. On microscopic examinations, no tumor cells were detected in the ulcer scar of the resected stomach or the regional lymph nodes. Thus, we discuss the potential of long-term NAC, especially for responders to two initial courses.
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16
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Surgical treatment for peritoneal carcinomatosis from gastric cancer. Eur J Surg Oncol 2010; 36:1131-8. [PMID: 20933363 DOI: 10.1016/j.ejso.2010.09.006] [Citation(s) in RCA: 90] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2010] [Revised: 06/28/2010] [Accepted: 09/02/2010] [Indexed: 12/20/2022] Open
Abstract
This review describes the latest surgical treatments for peritoneal carcinomatosis (PC) arising from gastric cancer. Systemic chemotherapy is less effective against PC because of the existence of the blood-peritoneal barrier. Accordingly, perioperative intraperitoneal chemotherapy plus cytoreductive surgery (CRS) is a new trend of multidisciplinary therapy for PC. Intraperitoneally administered drugs penetrate directly into the peritoneal dissemination, resulting in the high loco-regional intensity of drugs. A new bidirectional chemotherapy called neoadjuvant intraperitoneal/systemic chemotherapy (NIPS) has been developed. After NIPS, the disappearance of PFCCs has been reported, and the incidence of complete cytoreduction has increased accordingly. Complete cytoreduction, a low peritoneal carcinomatosis index, and negative PFCCs are significant favorable prognostic factors. Hyperthermic intraperitoneal chemotherapy (HIPEC) after CRS is associated with improved survival with an acceptable postoperative mortality and morbidity. Early postoperative intraperitoneal chemotherapy (EPIC) has also contributed to improving survival after CRS.
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17
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A phase II study of preoperative chemotherapy with S-1 plus cisplatin followed by D2/D3 gastrectomy for clinically serosa-positive gastric cancer (JACCRO GC-01 study). Eur J Surg Oncol 2010; 36:546-51. [PMID: 20541062 DOI: 10.1016/j.ejso.2010.04.011] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2009] [Revised: 03/25/2010] [Accepted: 04/12/2010] [Indexed: 12/17/2022] Open
Abstract
AIMS Clinically serosa-positive (T3-4) gastric cancer has a poor prognosis. This phase II trial explored the feasibility and safety of preoperative chemotherapy followed by D2 or D3 gastrectomy in this type of gastric cancer. METHODS Patients with T3-4 gastric cancer received one course of S-1 (80mg/m(2) daily for 3 weeks) and cisplatin (60mg/m(2) on day 8) chemotherapy and then underwent D2 or D3 gastrectomy with curative intent. Primary endpoint was toxicities. RESULTS Of 50 patients enrolled, 49 were eligible and received the treatment protocol. Chemotherapy-related toxicities were mild; grade 3 neutropenia in 2 patients, anorexia in 3, and nausea in 2, and no grade 4 toxicities. Clinical response was achieved in 13 of 34 evaluable patients. Of the 49 patients, 39 underwent D2 or D3 dissection. There was no surgical mortality. Operative morbidity occurred in 5 of 49 patients, including pancreatic fistula in 1 and abdominal abscess in 2. CONCLUSION This multi-modality treatment seems to be feasible and safe for T3-4 gastric cancer.
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18
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Yonemura Y, Elnemr A, Endou Y, Hirano M, Mizumoto A, Takao N, Ichinose M, Miura M, Li Y. Multidisciplinary therapy for treatment of patients with peritoneal carcinomatosis from gastric cancer. World J Gastrointest Oncol 2010; 2:85-97. [PMID: 21160926 PMCID: PMC2998933 DOI: 10.4251/wjgo.v2.i2.85] [Citation(s) in RCA: 87] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2009] [Revised: 12/05/2009] [Accepted: 12/12/2009] [Indexed: 02/05/2023] Open
Abstract
There is no standard treatment for peritoneal carcinomatosis (PC) from gastric cancer. A novel multidisciplinary treatment combining bidirectional chemotherapy [neoadjuvant intraperitoneal-systemic chemotherapy protocol (NIPS)], peritonectomy, hyperthermic intraperitoneal chemoperfusion (HIPEC) and early postoperative intraperitoneal chemotherapy has been developed. In this article, we assess the indications, safety and efficacy of this treatment, review the relevant studies and introduce our experiences. The aims of NIPS are stage reduction, the eradication of peritoneal free cancer cells, and an increased incidence of complete cytoreduction (CC-0) for PC. A complete response after NIPS was obtained in 15 (50%) out of 30 patients with PC. Thus, a significantly high incidence of CC-0 can be obtained in patients with a peritoneal cancer index (PCI) ≤ 6. Using a multivariate analysis to examine the survival benefit, CC-0 and NIPS are identified as significant indicators of a good outcome. However, the high morbidity and mortality rates associated with peritonectomy and perioperative chemotherapy make stringent patient selection important. The best indications for multidisciplinary therapy are localized PC (PCI ≤ 6) from resectable gastric cancer that can be completely removed during a peritonectomy. NIPS and complete cytoreduction are essential treatment modalities for improving the survival of patients with PC from gastric cancer.
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Affiliation(s)
- Yutaka Yonemura
- Yutaka Yonemura, Ayman Elnemr, NPO Organization to Support Peritoneal Dissemination Treatment, Kishiwada, Osaka 596-0032, Japan
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19
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Yonemura Y, Elnemr A, Endou Y, Hirano M, Mizumoto A, Takao N, Ichinose M, Miura M, Li Y. Multidisciplinary therapy for treatment of patients with peritoneal carcinomatosis from gastric cancer. World J Gastrointest Oncol 2010. [PMID: 21160926 DOI: 10.4251/wjgo.v2.i2.] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
There is no standard treatment for peritoneal carcinomatosis (PC) from gastric cancer. A novel multidisciplinary treatment combining bidirectional chemotherapy [neoadjuvant intraperitoneal-systemic chemotherapy protocol (NIPS)], peritonectomy, hyperthermic intraperitoneal chemoperfusion (HIPEC) and early postoperative intraperitoneal chemotherapy has been developed. In this article, we assess the indications, safety and efficacy of this treatment, review the relevant studies and introduce our experiences. The aims of NIPS are stage reduction, the eradication of peritoneal free cancer cells, and an increased incidence of complete cytoreduction (CC-0) for PC. A complete response after NIPS was obtained in 15 (50%) out of 30 patients with PC. Thus, a significantly high incidence of CC-0 can be obtained in patients with a peritoneal cancer index (PCI) ≤ 6. Using a multivariate analysis to examine the survival benefit, CC-0 and NIPS are identified as significant indicators of a good outcome. However, the high morbidity and mortality rates associated with peritonectomy and perioperative chemotherapy make stringent patient selection important. The best indications for multidisciplinary therapy are localized PC (PCI ≤ 6) from resectable gastric cancer that can be completely removed during a peritonectomy. NIPS and complete cytoreduction are essential treatment modalities for improving the survival of patients with PC from gastric cancer.
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Affiliation(s)
- Yutaka Yonemura
- Yutaka Yonemura, Ayman Elnemr, NPO Organization to Support Peritoneal Dissemination Treatment, Kishiwada, Osaka 596-0032, Japan
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20
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Yonemura Y, Endou Y, Shinbo M, Sasaki T, Hirano M, Mizumoto A, Matsuda T, Takao N, Ichinose M, Mizuno M, Miura M, Ikeda M, Ikeda S, Nakajima G, Yonemura J, Yuuba T, Masuda S, Kimura H, Matsuki N. Safety and efficacy of bidirectional chemotherapy for treatment of patients with peritoneal dissemination from gastric cancer: Selection for cytoreductive surgery. J Surg Oncol 2009; 100:311-6. [PMID: 19697437 DOI: 10.1002/jso.21324] [Citation(s) in RCA: 95] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
There is no standard treatment for peritoneal carcinomatosis (PC) from gastric cancer. New bidirectional chemotherapy (neoadjuvant intraperitoneal-systemic chemotherapy protocol (NIPS)) was developed. The aim of the present study was to assess the safety and efficacy of NIPS and to show the selection for cytoreductive surgery on PC from gastric cancer. Seventy-nine patients with PC from gastric cancer were treated with NIPS. A peritoneal port system was introduced into the abdominal cavity. The peritoneal wash cytological examination through a port was done before and after NIPS. The patients were treated with oral TS-1 twice a daily for 21 days, followed by a 1-week rest. On day 1, 8, and 15 from the start of oral TS-1 administration, 30 mg/m(2) of Docetaxel and 30 mg/m(2) of cisplatinum with 500 ml of saline were introduced into the peritoneal cavity through the port. A median course of oral TS-1 was 2.1 course and a median time of IP chemoterapy was 5.8. Peritoneal free cancer cells (PFCCs) had been detected in 65 (82.2%) patients before NIPS, and the positive cytology changed to be negative in 41 (63.0%) patients after NIPS. After NIPS, 41 patients underwent laparotomy, and complete cytoreduction was done in 32 (78%) patients. Complete cytoreduction was done in 27 (51.9%) of 52 patients with negative cytology but in only 4 (14.8%) of 27 patients with positive cytology (P < 0.001). Patients with negative cytology after NIPS survived significantly longer than those with positive cytology. The adverse effects after NIPS were mild and there was no treatment-related deaths. The grade 3/4 hematological adverse effects were found in 2 (2.6%) patients. Grade 3 renal toxicity and port site infection was found in three patients, respectively. NIPS using a port system is a safe and effective treatment for PC. Peritoneal wash cytology through a port system is a good indicator to select the patients to perform cytoreductive surgery.
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Affiliation(s)
- Yutaka Yonemura
- NPO Organization to Support Peritoneal Dissemination Treatment, Kishiwada, Osaka, Japan.
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Saif MW, Syrigos KN, Katirtzoglou NA. S-1: a promising new oral fluoropyrimidine derivative. Expert Opin Investig Drugs 2009; 18:335-48. [PMID: 19243284 DOI: 10.1517/13543780902729412] [Citation(s) in RCA: 72] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
S-1 is an oral fluoropyrimidine that is designed to improve the antitumor activity of 5-fluorouracil (5-FU) concomitantly with an intent to reduce its toxicity. S-1 consists of tegafur, a prodrug of 5-FU combined with two 5-FU biochemical modulators:5-chloro-2,4-dihydroxypyridine (gimeracil or CDHP), a competitive inhibitor of dihydropyrimidine dehydrogenase and oteracil potassium which inhibits phosphorylation of 5-FU in the gastrointestinal tract decreasing serious gastrointestinal toxicities,including nausea, vomiting, stomatitis and diarrhea. Being an oral agent, S-1 offers convenience of administration and prevents complications of central venous access such as infection, thrombosis and bleeding. S-1 has shown efficacy in both gastrointestinal as well non-gastrointestinal malignancies. The authors review the current literature and provide their expert opinion on the incorporation of S-1 in the treatment of solid malignancies [corrected].
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Affiliation(s)
- Muhammad Wasif Saif
- Yale University School of Medicine, Division of Medical Oncology, 333 Cedar Street, FMP 116 New Haven, CT 06520, USA.
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Abstract
Gastric cancer is the seventh and oesophageal cancer the ninth most common cancer in the UK, and >50% of patients present with locally advanced or metastatic disease. The incidence of oesophageal and oesophagogastric junctional tumours is increasing, making these important disease entities to understand and research. Despite improvements in surgical and peri-operative supportive care, 3-year overall survival with surgery alone for resectable disease is still poor. Outcomes in localised oesophageal cancer are improved with pre-operative chemotherapy, and in gastric cancer with peri-operative treatment or post-operative chemoradiotherapy. Oesophageal squamous cell carcinoma can be treated with definitive chemoradiotherapy as an alternative to surgery. While survival in patients presenting with metastatic disease is improved with the addition of systemic chemotherapy, median survival remains <1 year. Patients who are otherwise fit can be offered chemotherapy and this is superior to best supportive care. Regimens including a platinum and an anthracycline agent are favoured by the results of randomised trials. No standard second-line therapy has emerged. New research into taxanes has shown promising anti-cancer activity, and novel areas of investigation include incorporation of agents targeting vascular endothelial growth factor or epidermal growth factor receptor into standard regimens. This review focuses on the clinical trial evidence that dictates the optimal management of localised and advanced oesophagogastric cancer, focusing on pharmacotherapy. We examine areas of current research and highlight future therapeutic directions.
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Affiliation(s)
- Christopher Jackson
- Gastrointestinal and Lymphoma Units, Royal Marsden Hospital, London and Surrey, United Kingdom
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Lee JL, Kang HJ, Kang YK, Ryu MH, Chang HM, Kim TW, Sohn HJ, Kim H, Lee JS. Phase I/II study of 3-week combination of S-1 and cisplatin chemotherapy for metastatic or recurrent gastric cancer. Cancer Chemother Pharmacol 2007; 61:837-45. [PMID: 17579864 DOI: 10.1007/s00280-007-0541-5] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2007] [Accepted: 06/01/2007] [Indexed: 11/24/2022]
Abstract
PURPOSE To define the maximum-tolerated dose (MTD) of S-1, given daily for 2 weeks followed by a 1-week rest, with a fixed dose of cisplatin on the initial day, and to determine the activity and safety of this regimen at the recommended dose (RD) when used as first line treatment of advanced gastric cancer (AGC). PATIENTS AND METHODS Cisplatin was fixed at a dose of 60 mg/m2 on day 1 (D1) and the starting dose of S-1 was 60 mg/m2/day (30 mg/m2 bid) (level I) on D1 to D14, every 3 weeks. The dose of S-1 was increased by 5 mg/m2 bid up to 100 mg/m2/day (level V) unless the MTD was achieved. RESULTS Sixty-two eligible patients were enrolled. MTD was set at level V with two of three patients developing grade 3 diarrhea or febrile neutropenia. The RD was determined at level IV (90 mg/m2/day). After the first 20 patients were enrolled in phase II, the protocol was amended; the S-1 dose was reduced to 80 mg/m2/day (N=23) because of poor bone marrow recovery. The objective response was observed in 20 of 42 evaluable patients (48%). SD was achieved in 15 (36%). The median PFS was 5.3 months (95% CI, 4.6-6.0 months) with a median OS of 10.0 months (95% CI, 5.1-14.8 months). Grade 3-4 toxicities included neutropenia (33%), anemia (31%), and anorexia (24%). CONCLUSIONS The 3-week combination of cisplatin plus S-1 is active against AGC with favorable toxicitiy profiles. The phase II schedule or doses may need further refinements.
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Affiliation(s)
- Jae-Lyun Lee
- Division of Oncology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap-dong, Songpa-gu, Seoul, 138-736, South Korea
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24
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Nakajo A, Natsugoe S, Hokita S, Ishigami S, Takatori H, Arigami T, Uenosono Y, Aridome K, Aikou T. Successful treatment of advanced gastric cancer by surgical resection following combination chemotherapy with oral S-1 and biweekly paclitaxel. Gastric Cancer 2007; 10:58-62. [PMID: 17334720 DOI: 10.1007/s10120-006-0394-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2005] [Accepted: 07/26/2006] [Indexed: 02/07/2023]
Abstract
We report on the successful treatment of advanced gastric cancer by surgical resection following neoadjuvant chemotherapy. A 67-year-old man was referred to our hospital with a diagnosis of pancreatic cancer. Meticulous examination, however, revealed the presence of gastric cancer with ascites and large lymph node metastasis adjacent to the pancreas. We selected combination chemotherapy with oral S-1 and biweekly paclitaxel. After two courses, both the primary tumor and metastatic lymph nodes were greatly reduced, and the ascites had disappeared. Using laparoscopy, there was no evidence of peritoneal metastases, and the cytological examination was negative. The patient underwent distal gastrectomy with D2 lymph node dissection. Histological examination revealed that the cancer cells were still present in part, but no lymph node metastases were found. The tumor was pathologically diagnosed as pT2, pN0, P0, M0, CY0, and p-stage II. The patient is healthy over 4 years after surgery without recurrence.
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Affiliation(s)
- Akihiro Nakajo
- Department of Digestive Surgery and Surgical Oncology, Kagoshima University Graduate School of Medical & Dental Science, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
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Yamamoto M, Baba H, Toh Y, Okamura T, Maehara Y. Peritoneal lavage CEA/CA125 is a prognostic factor for gastric cancer patients. J Cancer Res Clin Oncol 2007; 133:471-6. [PMID: 17226046 DOI: 10.1007/s00432-006-0189-2] [Citation(s) in RCA: 67] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2006] [Accepted: 12/11/2006] [Indexed: 01/05/2023]
Abstract
BACKGROUND We recently found an elevation in the pre-operative peritoneal lavage carcinoembryonic antigen (CEA) level to be associated with an earlier detection of recurrent peritoneal dissemination and a poor prognosis. METHOD Two hundred and twenty-nine patients with gastric cancer were intraoperatively measured for tumor markers, CEA and CA125 based on peritoneal lavage using a chemiluminescent enzyme immunoassay. RESULTS The patients were divided into four groups. (A) The peritoneal lavage CEA (-) CA125 (-) group (CEA < 0.4 ng/ml, CA125 < 200 ng/ml, n = 129); (B) the peritoneal lavage CEA (-) CA125 (+) group (CEA < 0.4 ng/ml, CA125 >or= 200 ng/ml, n = 50); (C) the peritoneal lavage CEA (+) CA125 (-) group (CEA >or= 0.4 ng/ml, CA125 < 200 ng/ml, n = 18); and (D) the peritoneal lavage CEA (+) CA125 (+) group (CEA >or= 0.4 ng/ml, CA125 >or= 200 ng/ml, n = 32). The 5-year survival of the patients in groups C and D was 40 and 26%, respectively, which was lower than that of the patients in any other group (group A, B; p < 0.0001). Recurrent sites were both peritoneal dissemination and lymph node/liver in group C, while those were only peritoneal dissemination in group D. CONCLUSION This combined analysis of these markers is therefore considered to be helpful method to accurately estimate the recurrent sites and prognosis for advanced gastric cancer patients.
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Affiliation(s)
- Manabu Yamamoto
- Department of Surgery, Hiroshima Red Cross Hospital and Atomic Bomb Survivors Hospital, 1-9-6 Senda-machi, Hiroshima 730-8619, Japan.
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Kikuchi N, Shiozawa T, Ishii Y, Satoh H, Noguchi M, Ohtsuka M. A patient with pulmonary lymphangitic carcinomatosis successfully treated with TS-1 and cisplatin. Intern Med 2007; 46:491-4. [PMID: 17443041 DOI: 10.2169/internalmedicine.46.6363] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
A 37-year-old man was referred to our hospital with complaints of dyspnea and general fatigue. Chest radiograph and CT scan revealed thickness of bronchovascular bundles in both lungs. In spite of various examinations, the primary lesion was not identified. He received chemotherapy containing TS-1 and cisplatin. Pulmonary lymphangitic carcinomatosis disappeared and the patient achieved a good partial response. He survived for 14 months after the chemotherapy. We believe the combination of TS-1 and cisplatin is one of the attractive options for patients with cancer of unknown primary site.
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Affiliation(s)
- Norihiro Kikuchi
- Division of Respiratory Medicine, Institute of Clinical Medicine, University of Tsukuba
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27
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Kobayashi K, Tsuji A, Morita S, Horimi T, Shirasaka T, Kanematsu T. A phase II study of LFP therapy (5-FU (5-fluorourasil) continuous infusion (CVI) and Low-dose consecutive (Cisplatin) CDDP) in advanced biliary tract carcinoma. BMC Cancer 2006; 6:121. [PMID: 16677397 PMCID: PMC1483897 DOI: 10.1186/1471-2407-6-121] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2005] [Accepted: 05/06/2006] [Indexed: 11/14/2022] Open
Abstract
Background Unresectable biliary tract carcinoma is known to demonstrate a poor prognosis. We conducted a single arm phase II study of LFP therapy (5-FU (5-fluorourasil) continuous infusion (CVI) and Low-dose consecutive (Cisplatin) CDDP) for advanced biliary tract malignancies basically on an outpatient basis. Methods Between February 1996 and September 2003, 42 patients were enrolled in this trial. LFP therapy By using a total implanted CV-catheter system, 5-FU (160 mg/m2/day) was continuously infused over 24 hours for 7 consecutive days and CDDP (6 mg/m2/day) was infused for 30 minutes twice a week as one cycle. The administration schedule consisted of 4 cycles as one course. RESIST criteria (Response evaluation criteria for solid tumors) and NCI-CTC (National Cancer Institute-Common Toxicity Criteria) (ver.3.0) were used for evaluation of this therapy. The median survival time (MST) and median time to treatment failure (TTF) were calculated by the Kaplan-Meier method. Results Patients characteristics were: mean age 66.5(47–79): male 24 (54%): BDca (bile duct carcinoma) 27 GBca (Gallbladder carcinoma) 15: locally advanced 26, postoperative recurrence 16. The most common toxicity was anemia (26.2%). Neither any treatment related death nor grade 4 toxicity occurred. The median number of courses of LFP Therapy which patients could receive was two (1–14). All the patients are evaluable for effects with an over all response rates of 42.9% (95% confidence interval C.I.: 27.7–59.0) (0 CR, 18 PR, 13 NC, 11 PD). There was no significant difference regarding the anti tumor effects against both malignant neoplasms. Figure 2 Shows the BDca a longer MST and TTF than did GBca (234 vs 150, 117 vs 85, respectively), but neither difference was statistically significant. The estimated MST and median TTF were 225 and 107 days, respectively. The BDca had a longer MST and TTF than GBca (234 vs 150, 117 vs 85, respectively), but neither difference was statistically significant. Conclusion LFP therapy appears to be useful modality for the clinical management of advanced biliary tract malignancy.
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Affiliation(s)
- Kazuma Kobayashi
- Internal medicine, Clinical Oncology Group, Kochi Municipal Central Hospital, Kochi, Japan
- Department of Transplantation and Digestive Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Akihito Tsuji
- Department of Clinical Oncology, Kochi Health Science Center, Kochi, Japan
| | - Sojiro Morita
- Radiology, Clinical Oncology Group, Kochi Municipal Central Hospital, Kochi, Japan
| | - Tadashi Horimi
- Surgery, Clinical Oncology Group, Kochi Municipal Central Hospital, Kochi, Japan
| | | | - Takashi Kanematsu
- Department of Transplantation and Digestive Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
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28
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Ohashi S, Yazumi S, Nishio A, Fukui T, Asada M, Chiba T. Acute cerebral infarction during combination chemotherapy with s-1 and cisplatin for a young patient with a mucin-producing adenocarcinoma of the stomach. Intern Med 2006; 45:1049-53. [PMID: 17043376 DOI: 10.2169/internalmedicine.45.1720] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
We report a 29-year-old woman with gastric cancer who developed Trousseau's syndrome, a malignancy-related thromboembolism, during chemotherapy. She was diagnosed with a mucin-producing adenocarcinoma of the stomach, and chemotherapy with S-1 and cisplatin was commenced. During treatment, she developed a sudden onset of right hemiplegia. Magnetic resonance imaging showed an acute cerebral infarction of the left cerebral hemisphere. The underlying pathophysiology is thought to be chronic disseminated intravascular coagulation due to mucin-producing adenocarcinomas. However, cisplatin-induced vascular toxicity and hypercoagulability caused by decreased plasma protein C activity, elevated plasma von-Willebrand factor levels, and hypomagnesemia has also been proposed to be associated with thrombogenicity.
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Affiliation(s)
- Shinya Ohashi
- Department of Gastroenterology and Hepatology, Tazuke-Kofukai Medical Research Institute and Kitano Hospital, 2-4-20 Ogimachi, Kita-ku, Osaka 530-8480, Japan
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