A phase I trial of fixed dose rate gemcitabine plus capecitabine in metastatic cancer patients

Background: Capecitabine and gemcitabine given as fixed dose rate (FDR) has not been demonstrated to be well tolerated in phase I previous studies. The goals of this phase I study were to determine the maximum-tolerated dose of this combination and to describe the dose-limiting toxic effects (DLT) and the safety profile of this way of administration. Patients and methods: Patients with advanced solid tumors were eligible for this study. Capecitabine was administered orally at a dose of 650 mg/m(2) bis in die (b.i.d.) for 14 consecutive days. Gemcitabine was administered at FDR of 10 mg/m(2) per min in escalating durations of infusion on days 1 and 8. The cycles were repeated every 21 days. Results: All 20 patients enrolled into the study were assessable for toxicity. Only one out of the first six patients treated at FDR gemcitabine dose of 800 mg/m(2) met protocol-specified DLT criteria (grade 4 neutropenia lasting >= 7 days) during the first two cycles. At these doses the majority of cycles of therapy were, however, delivered without dose reduction or delay. Another similar episode of DLT was observed at the same dose step among the following eight included patients. The dose of FDR gemcitabine 800 mg/m(2) in 80 min on days 1 and 8 plus capecitabine 650 mg/m(2) b.i.d., for 14 consecutive days followed by 1 week of rest is recommended for further study. Conclusion: The combination of FDR gemcitabine plus capecitabine can be administered with acceptable toxicity. The evidence of antitumor activity deserves further investigation in phase II combination chemotherapy studies