Phase II study of induction chemotherapy with fixed dose rate (FDR) gemcitabine and cisplatin followed by concurrent chemoradiation with capecitabine for locally advanced pancreatic cancer (LAPC)

Abstract

15122 Background: Despite the use of 5-FU based chemoradiotherapy (CRT) over the past decades, prognosis of patients with LAPC remains dismal. To deliver more efficient systemic treatment earlier and reduce toxicity of CRT, we designed a treatment protocol consisting of induction (IND) chemotherapy with FDR gemcitabine (GEM) and cisplatin (CDDP), followed by CRT with capecitabine (CAP) in LAPC. Methods: Eligible patients had unresectable, histologically confirmed adenocarcinoma of pancreas, ECOG PS of 0–2, and no prior chemo- or radiotherapy for this phase II study. Patients received FDR GEM 1000 mg/m2 (D1,8) and CDDP 60 mg/m2 (D1) every 3 weeks for 3 cycles. Patients without disease progression subsequently received CRT of 55.8 Gy in 31 fractions concurrently with CAP, 650 mg/m2 given twice daily without drug holidays. Four weeks after CRT, FDR GEM 1000 mg/m2 was given on day 1, 8 every 3 weeks for 3 cycles. Time to progression was the primary endpoint. Results: Between Jan 2005 and Nov 2006, 21 patients were enrolled (median age 59, M/F: 13/8, ECOG PS 0/1: 3/18). Two patients withdrew consent after 1st and 2nd cycle and remaining 19 patients completed all three cycles of IND chemotherapy, with three (15.8%) out of 19 evaluable patients achieving partial response (0 CR, 3 PR, 14 SD, 2 PD). All 17 patients completed CRT with mean radiation dose of 55.4 Gy. Further four patients progressed during CRT, while one additional patient achieved partial response. As of Jan 2007, 5 patients died and 12 patients showed tumor progression. Median TTP was 12.5 mo (95% CI: 4.2–20.8) and median survival was not reached with median follow up duration of 9.7 months. Grade III/IV toxicities included neutropenia (38.1%/9.5%), thrombocytopenia (4.8%/0%), and anemia (14.3%/0%) during IND phase. Toxicites were generally mild during CRT phase with grade III neutropenia and diarrhea occurring in one and two patients, respectively. One patient died of neutropenic sepsis after 3rd cycle of IND chemotherapy. Conclusions: FDR GEM-CDDP induction chemotherapy followed by CAP-RT and maintenance FDR GEM is feasible and active with promising TTP of 12.5 months. Enrollment continues till reaching target accrual of 37 patients. No significant financial relationships to disclose.