Fixed dose rate (FDR) gemcitabine (G) and capecitabine (C) in patients with advanced and/or metastatic cancer: phase I trial

Abstract

12016 Background: Combination of C and G has been demonstrated to be well tolerated, with apparent efficacy in patients with advanced cancers. To determine the toxicity of C plus Fixed Dose Rate (FDR) G in metastatic cancer patients, a phase I trial was conducted. Methods: This is an open-label, single-center, dose-escalating phase I study. C was administered orally according to the standard 21-day schedule: bid in equal doses (650 mg/m2 bid) for 14 days every 21 days. G was administered at a FDR of 10 mg/m2 per min in escalating durations of infusion on days 1 and 8 every 21 days. The doses of G explored were 600, 700, 800 mg/m2 infused at FDR in 60, 70 and 80 minutes, respectively. 15 pts (10 female, 5 male), aged 37–70 yr (median 66) with a variety of advanced solid tumors have been treated (11 peri-ampullary cancers, 3 colorectal cancers and 1 ovarian cancer). The FDR G dose was escalated when 3 patients in a cohort had completed two cycles of treatment without experiencing dose-limiting toxicities (DLT). The MTD was defined as the dose level at which no more than one of nine patients experienced a DLT. Results: No DLT occurred at doses of 600 and 700 mg/m2 in any of the 3 patients included at each level. At 800 mg/m2, 1 of 9 patients experienced DLT (neutropenia grade 4 with fever). The non-haematological toxicities have been generally mild or moderate in all patients (grade 2 stomatitis: 4 patients; grade 2 fatigue: 3 patients; grade 2 nausea/vomiting: 2 patients). 2 patients showed one episode of grade 4 neutropenia spontaneously regressed in 3 days. 2 patients showed one episode of grade 2 thrombocytopenia. The recommended dose for further studies is C bid in equal doses (650 mg/m2 bid) for 14 days (28 doses) plus FDR G at 800 mg/m2 infused in 80 minutes on days 1 and 8 every 21 days. Other patients with periampullary carcinoma are being evaluated at the same dose level, with an ongoing evaluation of cumulative (all cycles) toxicity and efficacy. In terms of response, we have observed 2 PR and 3 SD in the 6 pancreatic cancer patients evaluated for response after the first 3 cycles. Conclusions: C plus FDR G combination seems to be a feasible and safety approach which has demonstrated promising clinical activity. No significant financial relationships to disclose.