297 Background: The purpose of this study was to determine the maximum tolerated dose (MTD), dose limiting toxicities (DLT), and efficacy of the second-line chemotherapy (after gemcitabine based chemotherapy) by FOLFIRINOX with unresectable pancreatic cancer. Methods: The subjects were histopathologically proven unresectable pancreatic cancer patients. The schedule was oxaliplatin 85mg/m2 on day1, irinotecan on day1, leucovorin 400mg/m2 on day 1 followed by FU 400mg/m2 as a bolus on day 1 and 2400mg/m2 as 46-hour continuous infusion biweekly. We were planned the dose of oxaliplatin, leucovorin and FU were fixed and the dose of irinotecan was defined as follows: level 0: 100mg/m2, level 1: 125mg/m2, level 2: 150mg/m2, and level 3: 180mg/m2. We started level 1 and at least three patients were enrolled at same dose two cycles. If DLT was observed two patients in six or three patients, we suspected the level was MTD. We also evaluated this study as phase II. Primary end point was response rate (RR). We also evaluated progression free survival (PFS), overall survival (OS) and adverse event (AE). Results: Eighteen patients were enrolled in this study (man: n = 11, woman: n = 7). We evaluated initial eight patients as phase I study. One patient had neutropenia and another one patient had hyperglycemia and severe infection. We decided level 1 was MTD and recommended dose was level 0. According to phase II study, RR was 22.2% (CR: n = 0, PR: n = 4, SD: n = 7, PD: n = 7) and disease control rate (DCR) was 61.1%. PFS was 2.8 (0.7-11.7) months and OS was 9.8 (2.4-14.4) months. The most common severe AE was neutropenia (66.7%). Fibril neutropenia was occurred one (5.6%) case. Conclusions: Recommended dose was oxaliplatin 85mg/m2 on day1, irinotecan 100mg/m2 on day1, leucovorin 400mg/m2 on day 1 followed by FU 400mg/m2 as a bolus on day 1 and 2400mg/m2 as 46-hour continuous infusion. RR was 22.2% and major AE was neutropenia but FN was rare. Second-line FOLFIRINOX is marginally effective treatment for gemcitabine-base chemotherapy failure cases.
Role of second-line chemotherapy in advanced pancreatic cancer and its influence on phase II/III study results
