Randomized phase II trial of TS-1 monotherapy versus TS-1 plus gemcitabine therapy in patients with gemcitabine-resistant advanced pancreatic cancer

INTERVENTION: Arm 1: S‐1 monotherapy Patients who enrolled this study will receive either arm of the therapy 3 weeks after their prior treatment has finished. In the S‐1 arm, S‐1 is given orally for four weeks, followed by a 2‐week rest. as two divided doses (after breakfast and dinner), determined according to body surface area (BSA): BSA below 1.25 m2, 80 mg; 1.25 to 1.5 m2, 100 mg and BSA over1.5 m2, 120 mg. This course is repeated until progressive disease or severe toxicities are confirmed. Arm 2: S‐1/Gem Patients who enrolled this study will receive either arm of the therapy 3 weeks after their prior treatment has finished. In the S‐1/Gem arm, Gemcitabine (1000 mg/m2) is given by intravenous infusion over 30 minutes on days 8 and 15, followed by a 1‐week rest. However, if the dose is reduced in patients during the first‐line chemotherapy, administration should be started after reducing the dose of gemcitabine to 800 mg/m2. S‐1 is given orally for two weeks from Day 1 to 14, followed by a 1‐week rest. as two divided doses (after breakfast and dinner), determined according to body surface area (BSA): BSA below 1.25 m2, 60 mg; 1.25 to 1.5 m2, 80 mg and BSA over1.5 m2, 100 mg. This course is repeated until progressive disease or severe toxicities are confirmed. CONDITION: Patients with unresectable advanced pancreatic cancer (Stage IV, TNM Classification) who were primarily resistant to gemcitabine monotherapy PRIMARY OUTCOME: disease control rate SECONDARY OUTCOME: progression‐free survival, overall survival, adverse event, QOL INCLUSION CRITERIA: Eligible criteria in this study are as follows: 1)Cases with clinically proven carcinoma of the pancreas 2) Stage IV (TMN classification, UICC) unresectable patients. 3) Ages between 20 to 80 years old 4) An Eastern Cooperative Oncology Group performance status of 0 or 1. (Karnofsky performance status (KPS) of 70%) 5) Patients with solid tumor(s) which can be evaluated by Response Evaluation Criteria in Solid Tumours (RECIST) guidelines 6) Patients who previously had received gemcitabine monotherapy as the first‐line chemotherapy and had been diagnosed as Progressive Disease (PD) 7) patients who experienced grade 4 hematologic toxicity are ineligible. 8) Patients must not have received any chemotherapy or radiotherapy for 3 weeks before entering this study 9) prior dose of the gemcitabine in the past chemotherapy>= 800 mg/m(2) 10) patients who are capable of oral intake. 11) Sufficient organ function within 1‐week from the enrol