A phase II study of gemcitabine (GEM) given at fixed-dose rate (FDR) infusion, low-dose cisplatin (CDDP), and bevacizumab (BEV) for metastatic adenocarcinoma of the pancreas (PanCa): Update with completion of study accrual

Abstract

4548 Background: The objectives of this study are to determine safety and efficacy in pts with metastatic PanCa treated with a novel combination consisting of FDR GEM, low-dose CDDP, and BEV. We present here updated results on the full 53-pt study cohort. Methods: Chemotherapy-naive pts with histologically confirmed PanCa and documented extrapancreatic metastases received GEM 1,000 mg/m2 at FDR infusion (10 mg/m2/min), CDDP 20 mg/m2, and BEV 10 mg/kg, all administered on dd 1 and 15 of a 28-dd cycle. Pts were monitored by CT scans every 2 cycles and monthly serum CA19–9 measurements. Results: 53 pts (24M,29F; median age 60 y.o. [range 39–85]; ECOG PS 0–1) were enrolled betw 6/2004 and 9/2006 (med f/u, 513 dd; range, 93–885). 16 pts remain alive, with 9 still undergoing study rx. Pts received a median of 4.75 cycles of rx (range, 0.5–20). 29 pts discontinued study rx 2o to progressive dz (med # of cycles, 5; range, 0.5–20); 9 pts 2o to rx-assoc toxicity; 4 pts 2o to plateau in response with cumulative asthenia (after 8–12 cycles); and 2 pts 2o to prolonged rx delay from bowel obstruction. Major events include 2 bowel perforations, one associated with placement of a duodenal stent; 4 major GI bleeds; 7 DVT/PE; 1 stroke-like sxs; and 3 cardiac events (MI x 1, arrhythmias x 2). 4 pts (7.5%) developed grade 3/4 HTN. Gr 3/4 hematologic toxicities inc. neutropenia in 4 pts (7.5%) and thrombocytopenia in 1 pt (2.9%). 16 pts (20%) required dose reduction in gemcitabine during study rx and 4 required holding of cisplatin. There were 3 deaths potentially assoc with rx. 12 pts (22.6%) have had an unconfirmed response (1 CR, 11 PR) and 26 pts (49.1%) have had stable dz for >2 cycles, for an overall dz control rate of 71.7%. 20 of 35 pts (57.1%) with elev baseline CA19–9 levels (>2X ULN) had >50% biomarker decline during rx. Median TTP is 6.2 months. Median overall survival is 8.0 months with an est. 1-yr survival rate of 40%. Conclusions: The addition of BEV to FDR GEM/low-dose CDDP shows promising efficacy, particularly in TTP and 1-yr survival rate, with manageable toxicity. Further efforts are ongoing to identify which pts are most likely to benefit from BEV-based rx. [Table: see text]