Pemetrexed and gemcitabine for biliary tract and gallbladder carcinomas: A north central cancer treatment group (NCCTG) phase i and II trial, N9943

Purpose: To determine the maximum tolerated dose (MTD) and efficacy of pemetrexed and gemcitabine in patients with either biliary tract or gallbladder carcinoma. Patients and Methods: Patients with unresectable previously untreated biliary tract cancers were eligible for participation. An initial phase I trial was performed to determine the MTD using an every-2-weeks schedule. The MTD was then used in the phase II portion of the trial. The primary end point for the phase II portion was 6-month survival with a planned accrual of 59 patients. Results: Overall, 63 eligible patients were enrolled. The MTD was established as pemetrexed 500 mg/m² IV over 10 min and gemcitabine 800 mg/m ² IV at 10 mg/m² per minute on days 1 and 15 of an every-4-weeks schedule with vitamin B12 and folate supplementation. Fifty-eight patients were included in the phase II portion. Median age was 61 and median follow-up was 18.2 months. A median of three cycles of treatment was given. Six-month survival was 55% and the median survival was 6.6 months (95% confidence interval 5.4-8.7 months) with a median time to progression of 3.8 months (2.4-5.4). Forty-seven (81%) experienced at least one grade 3+ adverse event, and 28 patients (48%) experienced at least one grade 4 adverse event, most of which were due to grade 4 neutropenia. Conclusion: The addition of pemetrexed to fixed-dose-rate gemcitabine, in a biweekly schedule, did not enhance the activity of gemcitabine in patients with biliary tract or gallbladder carcinoma.