AIM: To evaluate the dose-limiting toxicities(DLTs)and determine the maximum-tolerated dose(MTD) and recommended dose(RD) of combination chemotherapy with gemcitabine, cisplatin and S-1 which is an oral fluoropyrimidi...AIM: To evaluate the dose-limiting toxicities(DLTs)and determine the maximum-tolerated dose(MTD) and recommended dose(RD) of combination chemotherapy with gemcitabine, cisplatin and S-1 which is an oral fluoropyrimidine pro-drug in patients with advanced biliary tract cancer.METHODS: Patients with histologically or cytologically confirmed unresectable or recurrent biliary tract cancer were enrolled. The planned dose levels of gemcitabine(mg/m2), cisplatin(mg/m2), and S-1(mg/m2 per day) were as follows: level-1, 800/20/60;level 0, 800/25/60; level 1, 1000/25/60; and level 2,1000/25/80. In each cycle, gemcitabine and cisplatin were administered intravenously on days 1 and 15,and S-1 was administered orally twice daily on days 1to 7 and days 15 to 21, every 4 wk.RESULTS: Twelve patients were enrolled, and level0 was chosen as the starting dose. None of the first three patients had DLTs at level 0, and the dose was escalated to level 1. One of six patients had DLTs(grade 4 febrile neutropenia, leucopenia, and neutropenia; grade 3 thrombocytopenia) at level 1.We then proceeded to level 2. None of three patients had DLTs during the first cycle. Although the MTD was not determined, level 2 was designated at the RD for a subsequent phase Ⅱ study.CONCLUSION: The RD was defined as gemcitabine1000 mg/m2(days 1, 15), cisplatin 25 mg/m2(days1, 15), and S-1 80 mg/m2 per day(days 1-7, 15-21),every 4 weeks. A phase Ⅱ study is planned to evaluate the effectiveness of combination chemotherapy withgemcitabine, cisplatin, and S-1 in advanced biliary tract cancer.展开更多
Background: Despite there are a few reports that assessed the S-1 + CDDP regimen with short hydration regimen for unresectable or metastatic gastric cancer, there is no consensus on the best regimen for short hydratio...Background: Despite there are a few reports that assessed the S-1 + CDDP regimen with short hydration regimen for unresectable or metastatic gastric cancer, there is no consensus on the best regimen for short hydration. The aim of study was to evaluate the safety and the efficacy of S-1 plus cisplatin doublet chemotherapy with short hydration. Methods: S-1 was administered orally (p.o.) twice daily for the first 3 weeks of a 5-week cycle. Dose of S-1 administered was calculated according to the body surface area. CDDP was given as an intravenous (i.v.) infusion of 60 mg/m2 on day 8 of each cycle. Patients received the total of 1900 ml infusion containing 1000 ml of acetate Ringer’s solution as pre- and post-hydraion. 300 ml of 20% mannitol was administered as a diuretic. Results: 35 patients with unresectable or recurrent gastric cancer were enrolled. The reasons for termination of S-1 + CDDP were as follows: 21 (63.6%) by progressive disease;12 (31.4%) by toxicity. Even though 12 of 35 patients (34.2%) were discontinued S-1 + CDDP chemotherapy, only one patient was discontinued by Grade 2 of increased creatinine. TTF (time to progression) was 174 days (3 - 586 days), and the median of the total number of treatment cycles of S-1 + CDDP was 3.31. Median overall survival, as secondary endpoint, was 518 days. Conclusions: Our study suggested that the short hydration regimen is as safe and efficient as the continuous hydration regimen.展开更多
Objective: To evaluate the feasibility of S-1 and high-dose cisplatin short hydration regimens for outpatients with unresectable metastatic gastric cancer. Methods: Data for individual outpatients treated in our insti...Objective: To evaluate the feasibility of S-1 and high-dose cisplatin short hydration regimens for outpatients with unresectable metastatic gastric cancer. Methods: Data for individual outpatients treated in our institution were retrospectively pooled to assess the feasibility of an S-1 and highdose cisplatin short hydration regimen (S-1: 80 to 120 mg on Days 1 to 21;cisplatin: 60 mg/m2?on Day 8, every 5 weeks), which included 2250 ml of intravenous fluids and 1000 ml oral hydration. Ten consecutive patients were treated with S-1 and high-dose cisplatin short hydration for unresectable metastatic gastric cancer from July 2011 to May 2012 and were included in the analysis. Results: With a median of 3.5 medication cycles, unscheduled admission occurred in two patients for 5 days each due to paralytic ileus and cerebral infarction. Four patients required dose reduction, in both S-1 and cisplatin in two patients, and in S-1 alone and cisplatin alone in one patient each. Renal function transiently declined after administration of cisplatin, but serum creatinine level and estimated glomerular filtration rate were both improved by the time of the next administration. Conclusion: This study suggests that an S-1 and high-dose cisplatin short hydration strategy for outpatients with unresectable metastatic gastric cancer might be feasible.展开更多
BACKGROUND： Pancreatic cancer is one of the most aggressive malignancies and chemotherapy is an effective strategy for advanced pancreatic cancer. Gemcitabine （GEM） is one of first-line agents. However, GEM-based c...BACKGROUND： Pancreatic cancer is one of the most aggressive malignancies and chemotherapy is an effective strategy for advanced pancreatic cancer. Gemcitabine （GEM） is one of first-line agents. However, GEM-based combination therapy has shown promising efficacy in patients with advanced pancreatic cancer. This meta-analysis aimed to compare the efficacy and safety of GEM-based combination therapy versus GEM alone in the treatment of advanced pancreatic cancer.DATA SOURCES： A comprehensive search of literature was performed using PubMed, EMBASE, Web of Science and Cochrane Central Register of Controlled Trials. A quantitative meta-analysis was performed based on the inclusion criteria from all eligible randomized controlled trials. The outcome indicators included overall survival （OS）, 6-month survival, 1-year survival, progression-free survival/time-to-progression （PFS/TTP）, and toxicities. RESULTS： A total of nine randomized controlled trials involving 1661 patients were included in this meta-analysis. There was significant improvement in the GEM-based combination therapy with regard to the OS （HR=0.85, 95% CI： 0.76-0.95, P=0.003）, PFS （HR=0.76, 95% CI： 0.65-0.90, P-0.002）, 6-month survival （RR=1.09, 95% CI： 1.01-1.17, P=0.03）, and the overall toxicity （RR=l.68, 95% CI： 1.52-1.86, P〈0.01）. However, there was no significant difference in the 1-year survival.CONCLUSIONS： GEM-based combination chemotherapy might improve the OS, 6-month survival, and PFS in advanced pancreatic cancer. However, combined therapy also added toxicity.展开更多
Gemcitabine chemotherapy has been the standard for advanced pancreatic cancer for more than a decade.New oral fluoropyrimidines such as S-1 and capecitabine are other key drugs.Gemcitabine plus erlotinib was the only ...Gemcitabine chemotherapy has been the standard for advanced pancreatic cancer for more than a decade.New oral fluoropyrimidines such as S-1 and capecitabine are other key drugs.Gemcitabine plus erlotinib was the only combination therapy that significantly prolonged survival,although the effect was minimal.Little or no improvement in survival with recent moleculartargeted drugs might be attributed to the very high incidence of K-ras gene mutation in pancreatic cancer.Recently,the non-gemcitabine-based-regimen of FOLFIRINOX showed significantly greater overall survival compared with gemcitabine for the first time.For biliary tract cancer,gemcitabine plus cisplatin combination chemotherapy has been proved to significantly prolong survival and will become the standard therapy.Further improvement in survival is expected by the addition of cetuximab.展开更多
Background: We have developed a new next-generation intrapleural hyperthermic chemotherapy (IPHC) for non-small cell lung cancer with dissemination, which is a hybrid chemotherapy combined with oral S-1 medication plu...Background: We have developed a new next-generation intrapleural hyperthermic chemotherapy (IPHC) for non-small cell lung cancer with dissemination, which is a hybrid chemotherapy combined with oral S-1 medication plus conventional cisplatin-based IPHC. We now report the preliminary feasibility and outcome of quality of life (QOL) regarding this hybrid IPHC. Methods: The patient was a 76-year-old male with a 2-cm nodule in the left upper lobe. After partial resection by video-assisted thoracic surgery (VATS), which was diagnosed with advanced pulmonary adenocarcinoma with intrapleural dissemination. We initially performed two regimens of systemic chemotherapy, S-1 (day 1 - 21, 100 mg 2X/day) + CDDP (day 8, 60 mg/m<sup>2</sup>) and S-1 (day 1 - 14,100 mg 2X/day) + CBDCA (day 1, AUC 5). The regimen of next-generation IPHC is oral S-1 medication (day 1 - 21, 100 mg/day) + intrapleural hyperthermic perfusion of cisplatin (200 mg/m<sup>2</sup>) with VATS (day 8,43°C, 2 hours). Adverse outcomes, QOL, and pleural effusion were assessed in three regimens. To investigate the outcomes of the QOL, the European Organization for Research and Treatment of Cancer QOL Questionnaire (EORTC QLQ-C30 and QLQ-LC13), the QOL questionnaire for cancer patients treated with anticancer drugs (QOL-ACD), the Cancer Dyspnea Score (CDS), and the St. George’s Respiratory Questionnaire (SGRQ) were used. Results: During the IPHC treatment course, grade 3 neutropenia, anemia, and diarrhea were observed. The physical function after IPHC became worse compared to that before the IPHC. Fatigue during chemotherapy (CBDCA+S-1) was more pronounced than that during the IPHC. Nausea, vomiting, and diarrhea during the IPHC were prevalent than those of chemotherapy. The overall QOL after the IPHC was improved compared to that before the IPHC. Regarding before and after the IPHC, the physical function after the IPHC became worse compared to that before the IPHC, on the other hand, the global QOL before and after the IPHC had not dramatically changed. Pleural effusion was controlled after the IPHC for more than 1 year. Conclusion: The first case of a clinical trial of the next-generation IPHC showed grade 3 adverse events. However, it was an acceptable feasibility compared to the usual platinum doublet chemotherapy. The effectiveness of the IPHC allowed the patient to obtain a good control of the pleural effusion and preserved the patient’s QOL.展开更多
A 72-year-old male gastric cancer patient with outlet obstruction underwent laparoscopic exploration. The examination disclosed intraperitoneal free cancer cells with no overt peritoneal, lymphatic, or hepatic metasta...A 72-year-old male gastric cancer patient with outlet obstruction underwent laparoscopic exploration. The examination disclosed intraperitoneal free cancer cells with no overt peritoneal, lymphatic, or hepatic metastasis. The patient underwent laparoscopy-assisted gastroje-junostomy (LAGJ) and started chemotherapy with S-1 plus cisplatin on postoperative day 13. Three course of the chemotherapy shrank the tumor markedly. Then, the patient underwent gastrectomy with a curative intent. Laparotomy revealed no intraperitoneal free cancer cells, and microscopically complete resection was achieved. The patient received S-1 chemotherapy as postoperative adjuvant treatment for 1 year, and is still alive with no evidence of peritoneal recurrence. LAGJ followed by S-1 plus cisplatin is one of the optional treatments that should be considered for patients with outlet obstruction as it may widen opportunities for potentially curative resection.展开更多
3多西紫杉醇、顺铂及S-1在局部复发转移的晚期头颈鳞癌中的Ⅰ、Ⅱ期研究 Phase I/II study of docetaxel, cisplatin and S-1 in local- ly advanced, recurrent and metastatic head and neck squamous cell carcinoma.Tada Y, Maruya...3多西紫杉醇、顺铂及S-1在局部复发转移的晚期头颈鳞癌中的Ⅰ、Ⅱ期研究 Phase I/II study of docetaxel, cisplatin and S-1 in local- ly advanced, recurrent and metastatic head and neck squamous cell carcinoma.Tada Y, Maruya SI, Saotome T, et al.Oncol Lett, 2012,4（5）：898-904.展开更多
文摘AIM: To evaluate the dose-limiting toxicities(DLTs)and determine the maximum-tolerated dose(MTD) and recommended dose(RD) of combination chemotherapy with gemcitabine, cisplatin and S-1 which is an oral fluoropyrimidine pro-drug in patients with advanced biliary tract cancer.METHODS: Patients with histologically or cytologically confirmed unresectable or recurrent biliary tract cancer were enrolled. The planned dose levels of gemcitabine(mg/m2), cisplatin(mg/m2), and S-1(mg/m2 per day) were as follows: level-1, 800/20/60;level 0, 800/25/60; level 1, 1000/25/60; and level 2,1000/25/80. In each cycle, gemcitabine and cisplatin were administered intravenously on days 1 and 15,and S-1 was administered orally twice daily on days 1to 7 and days 15 to 21, every 4 wk.RESULTS: Twelve patients were enrolled, and level0 was chosen as the starting dose. None of the first three patients had DLTs at level 0, and the dose was escalated to level 1. One of six patients had DLTs(grade 4 febrile neutropenia, leucopenia, and neutropenia; grade 3 thrombocytopenia) at level 1.We then proceeded to level 2. None of three patients had DLTs during the first cycle. Although the MTD was not determined, level 2 was designated at the RD for a subsequent phase Ⅱ study.CONCLUSION: The RD was defined as gemcitabine1000 mg/m2(days 1, 15), cisplatin 25 mg/m2(days1, 15), and S-1 80 mg/m2 per day(days 1-7, 15-21),every 4 weeks. A phase Ⅱ study is planned to evaluate the effectiveness of combination chemotherapy withgemcitabine, cisplatin, and S-1 in advanced biliary tract cancer.
文摘Background: Despite there are a few reports that assessed the S-1 + CDDP regimen with short hydration regimen for unresectable or metastatic gastric cancer, there is no consensus on the best regimen for short hydration. The aim of study was to evaluate the safety and the efficacy of S-1 plus cisplatin doublet chemotherapy with short hydration. Methods: S-1 was administered orally (p.o.) twice daily for the first 3 weeks of a 5-week cycle. Dose of S-1 administered was calculated according to the body surface area. CDDP was given as an intravenous (i.v.) infusion of 60 mg/m2 on day 8 of each cycle. Patients received the total of 1900 ml infusion containing 1000 ml of acetate Ringer’s solution as pre- and post-hydraion. 300 ml of 20% mannitol was administered as a diuretic. Results: 35 patients with unresectable or recurrent gastric cancer were enrolled. The reasons for termination of S-1 + CDDP were as follows: 21 (63.6%) by progressive disease;12 (31.4%) by toxicity. Even though 12 of 35 patients (34.2%) were discontinued S-1 + CDDP chemotherapy, only one patient was discontinued by Grade 2 of increased creatinine. TTF (time to progression) was 174 days (3 - 586 days), and the median of the total number of treatment cycles of S-1 + CDDP was 3.31. Median overall survival, as secondary endpoint, was 518 days. Conclusions: Our study suggested that the short hydration regimen is as safe and efficient as the continuous hydration regimen.
文摘Objective: To evaluate the feasibility of S-1 and high-dose cisplatin short hydration regimens for outpatients with unresectable metastatic gastric cancer. Methods: Data for individual outpatients treated in our institution were retrospectively pooled to assess the feasibility of an S-1 and highdose cisplatin short hydration regimen (S-1: 80 to 120 mg on Days 1 to 21;cisplatin: 60 mg/m2?on Day 8, every 5 weeks), which included 2250 ml of intravenous fluids and 1000 ml oral hydration. Ten consecutive patients were treated with S-1 and high-dose cisplatin short hydration for unresectable metastatic gastric cancer from July 2011 to May 2012 and were included in the analysis. Results: With a median of 3.5 medication cycles, unscheduled admission occurred in two patients for 5 days each due to paralytic ileus and cerebral infarction. Four patients required dose reduction, in both S-1 and cisplatin in two patients, and in S-1 alone and cisplatin alone in one patient each. Renal function transiently declined after administration of cisplatin, but serum creatinine level and estimated glomerular filtration rate were both improved by the time of the next administration. Conclusion: This study suggests that an S-1 and high-dose cisplatin short hydration strategy for outpatients with unresectable metastatic gastric cancer might be feasible.
基金supported by grants from the Scientific Research Foundation of Traditional Chinese Medicine of Zhejiang Province(2015ZA081)Zhejiang Provincial Natural Science Foundation of China(LY14H030006)+1 种基金Foundation for Young Scientists of Zhejiang Province Traditional Chinese Medicine(2011ZQ008)the Health and Family Planning Committee of Zhejiang Province(2012KYB143)
文摘BACKGROUND： Pancreatic cancer is one of the most aggressive malignancies and chemotherapy is an effective strategy for advanced pancreatic cancer. Gemcitabine （GEM） is one of first-line agents. However, GEM-based combination therapy has shown promising efficacy in patients with advanced pancreatic cancer. This meta-analysis aimed to compare the efficacy and safety of GEM-based combination therapy versus GEM alone in the treatment of advanced pancreatic cancer.DATA SOURCES： A comprehensive search of literature was performed using PubMed, EMBASE, Web of Science and Cochrane Central Register of Controlled Trials. A quantitative meta-analysis was performed based on the inclusion criteria from all eligible randomized controlled trials. The outcome indicators included overall survival （OS）, 6-month survival, 1-year survival, progression-free survival/time-to-progression （PFS/TTP）, and toxicities. RESULTS： A total of nine randomized controlled trials involving 1661 patients were included in this meta-analysis. There was significant improvement in the GEM-based combination therapy with regard to the OS （HR=0.85, 95% CI： 0.76-0.95, P=0.003）, PFS （HR=0.76, 95% CI： 0.65-0.90, P-0.002）, 6-month survival （RR=1.09, 95% CI： 1.01-1.17, P=0.03）, and the overall toxicity （RR=l.68, 95% CI： 1.52-1.86, P〈0.01）. However, there was no significant difference in the 1-year survival.CONCLUSIONS： GEM-based combination chemotherapy might improve the OS, 6-month survival, and PFS in advanced pancreatic cancer. However, combined therapy also added toxicity.
文摘Gemcitabine chemotherapy has been the standard for advanced pancreatic cancer for more than a decade.New oral fluoropyrimidines such as S-1 and capecitabine are other key drugs.Gemcitabine plus erlotinib was the only combination therapy that significantly prolonged survival,although the effect was minimal.Little or no improvement in survival with recent moleculartargeted drugs might be attributed to the very high incidence of K-ras gene mutation in pancreatic cancer.Recently,the non-gemcitabine-based-regimen of FOLFIRINOX showed significantly greater overall survival compared with gemcitabine for the first time.For biliary tract cancer,gemcitabine plus cisplatin combination chemotherapy has been proved to significantly prolong survival and will become the standard therapy.Further improvement in survival is expected by the addition of cetuximab.
文摘Background: We have developed a new next-generation intrapleural hyperthermic chemotherapy (IPHC) for non-small cell lung cancer with dissemination, which is a hybrid chemotherapy combined with oral S-1 medication plus conventional cisplatin-based IPHC. We now report the preliminary feasibility and outcome of quality of life (QOL) regarding this hybrid IPHC. Methods: The patient was a 76-year-old male with a 2-cm nodule in the left upper lobe. After partial resection by video-assisted thoracic surgery (VATS), which was diagnosed with advanced pulmonary adenocarcinoma with intrapleural dissemination. We initially performed two regimens of systemic chemotherapy, S-1 (day 1 - 21, 100 mg 2X/day) + CDDP (day 8, 60 mg/m<sup>2</sup>) and S-1 (day 1 - 14,100 mg 2X/day) + CBDCA (day 1, AUC 5). The regimen of next-generation IPHC is oral S-1 medication (day 1 - 21, 100 mg/day) + intrapleural hyperthermic perfusion of cisplatin (200 mg/m<sup>2</sup>) with VATS (day 8,43°C, 2 hours). Adverse outcomes, QOL, and pleural effusion were assessed in three regimens. To investigate the outcomes of the QOL, the European Organization for Research and Treatment of Cancer QOL Questionnaire (EORTC QLQ-C30 and QLQ-LC13), the QOL questionnaire for cancer patients treated with anticancer drugs (QOL-ACD), the Cancer Dyspnea Score (CDS), and the St. George’s Respiratory Questionnaire (SGRQ) were used. Results: During the IPHC treatment course, grade 3 neutropenia, anemia, and diarrhea were observed. The physical function after IPHC became worse compared to that before the IPHC. Fatigue during chemotherapy (CBDCA+S-1) was more pronounced than that during the IPHC. Nausea, vomiting, and diarrhea during the IPHC were prevalent than those of chemotherapy. The overall QOL after the IPHC was improved compared to that before the IPHC. Regarding before and after the IPHC, the physical function after the IPHC became worse compared to that before the IPHC, on the other hand, the global QOL before and after the IPHC had not dramatically changed. Pleural effusion was controlled after the IPHC for more than 1 year. Conclusion: The first case of a clinical trial of the next-generation IPHC showed grade 3 adverse events. However, it was an acceptable feasibility compared to the usual platinum doublet chemotherapy. The effectiveness of the IPHC allowed the patient to obtain a good control of the pleural effusion and preserved the patient’s QOL.
文摘A 72-year-old male gastric cancer patient with outlet obstruction underwent laparoscopic exploration. The examination disclosed intraperitoneal free cancer cells with no overt peritoneal, lymphatic, or hepatic metastasis. The patient underwent laparoscopy-assisted gastroje-junostomy (LAGJ) and started chemotherapy with S-1 plus cisplatin on postoperative day 13. Three course of the chemotherapy shrank the tumor markedly. Then, the patient underwent gastrectomy with a curative intent. Laparotomy revealed no intraperitoneal free cancer cells, and microscopically complete resection was achieved. The patient received S-1 chemotherapy as postoperative adjuvant treatment for 1 year, and is still alive with no evidence of peritoneal recurrence. LAGJ followed by S-1 plus cisplatin is one of the optional treatments that should be considered for patients with outlet obstruction as it may widen opportunities for potentially curative resection.
文摘3多西紫杉醇、顺铂及S-1在局部复发转移的晚期头颈鳞癌中的Ⅰ、Ⅱ期研究 Phase I/II study of docetaxel, cisplatin and S-1 in local- ly advanced, recurrent and metastatic head and neck squamous cell carcinoma.Tada Y, Maruya SI, Saotome T, et al.Oncol Lett, 2012,4（5）：898-904.
