e15502 Background: There are no standard chemotherapeutic regimens for incurable biliary adenocarcinomas. Monotherapies with gemcitabine or FU/LV achieve occasional responses and a median overall survival of about 6 months. By blocking PDGFR a decreased intrastromal pressure may increase therapy effects of chemotherapy. The combination of imatinib and FU/LV has been shown to be safe and feasible in a previous Phase I trial. This multicenter phase II trial was designed to investigate the disease control rate (DCR) of FU/LV and imatinib. Methods: Eligibility criteria included unresectable or metastatic measurable biliary tract cancer (BTC)/gallbladder cancer (GBC), performance status < 2, adequate organ function and no clinically significant cardiovascular disease. Enrolment of 44 chemonaive patients (pts.) was planned. Pts. received LV 200 mg/m2 followed by FU 2000 mg/m2 as a 24-hour infusion on days 1 and 2 combined with 600mg imatinib on days -4 to 4 (8 days). Cycles were repeated every 2 weeks up to 12 cycles. Radiological assessments were performed every 4 cycles. Results: 41 pts (19 GBC; 22 BTC) were enrolled in this phase II study since May 2007. Median age was 62 years (range 33–77), male/female=24/17, ECOG 0/1/2=13/23/5. 35 pts. showed metastatic disease at baseline. Treatment was well tolerated. Treatment related grade 3/4 toxicities included (number of pts): diarrhea (2), edema (1), neutropenia (2), nausea (2), transient SGPT elevation (4). The DCR of 26 pts. available for response assessment at time of analysis 1 was 58% (15 pts) (1 CR, 1 PR,13 SD of at least 4 cycles). 11 pts. showed progressive disease (PD) per RECIST criteria. 3 pts. had disease stabilization after 12 cycles and continue on treatment. We present these preliminary data as they represent a large patient number in this entity and response data are promising. Conclusions: This preliminary analysis suggests that the combination of FU/LV and imatinib can be safely administrated in pts. with GBC/BTC. Early evidence of antitumor activity was seen with some pts. achieving long term stabilization of the disease. [Table: see text]
Phase II trial of low-dose cyclo-phosphamide, leucovorin, high-dose 5-fluorouracil 24-hour continuous infusion and tamoxifen in advanced biliary tract cancer