A phase I trial of fixed dose rate gemcitabine and capecitabine in metastatic renal cell carcinoma.

Background: Metastatic renal cell carcinoma (RCC) has modest response rates to chemotherapy with gemcitabine and 5-fluorouracil (5-FU). Fixed dose rate gemcitabine infusion leads to enhanced intracellular accumulation of drug and possible augmented clinical effect. To determine the toxicity of this combination therapy in metastatic RCC, a Phase I trial was conducted.

Methods: Patients with metastatic RCC were enrolled in a Phase I dose escalation trial. Patients received fixed dose rate gemcitabine on Days 1, 8, and 15 in combination with capecitabine, an oral 5-FU analog, given on Days 1-21 of a 28-day cycle.

Results: Nine patients were enrolled at one of two dose levels. The initial dose level produced dose-limiting toxicity (DLT), including prominent palmar-plantar erythrodysesthesia (hand-foot syndrome). A modified second dose level also resulted in DLT, precluding further study. No central nervous system (CNS) toxicity was observed in three patients with CNS metastases. Two patients demonstrated an objective partial response.

Conclusions: Fixed dose rate gemcitabine in combination with capecitabine produced unacceptable toxicity in patients with advanced RCC. Further development of this schedule in RCC cannot be recommended.