A phase II study of flavopiridol in patients with advanced renal cell carcinoma: results of Southwest Oncology Group Trial 0109

Purpose: Flavopiridol is a cyclin-dependent kinase inhibitor that prevents cell cycle progression and tumor growth. In initial phase I studies, encouraging responses were seen in advanced renal cell cancer (RCC). In a phase II study of. avopiridol given as a 72-h continuous infusion every 2 weeks in RCC, a response rate of 6% was seen but with considerable grade 3 or 4 asthenia, diarrhea, and thrombosis. Subsequently, an alternative 1-h bolus schedule was reported to have enhanced tolerability in a phase I trial. We therefore conducted a phase II study of this bolus regimen. Methods: A total of 38 patients with advanced RCC were entered into this multi-institutional phase II study. Flavopiridol ( 50 mg/m(2) per day) was administered by bolus intravenous injection daily for three consecutive days, repeated every 3 weeks. Results: Out of 34 eligible patients, one complete response and three partial responses were observed, for an overall response rate of 12% (95% CI 3 - 27%). Of the 34 patients, 14 (41%) had stable disease (SD). The probability of not failing treatment by 6 months was 21% ( 95% CI 9 - 35%). Median overall survival time was 9 months ( 95% CI 8 - 18 months). The most common grade 3 or 4 toxicities were diarrhea ( 35%) and tumor pain ( 12%) along with anemia, dyspnea, and fatigue (9% each). Conclusions: Flavopiridol at this dose and schedule is feasible with an acceptable toxicity pro. le. Flavopiridol has some modest biologic activity against advanced RCC, as evidenced by its single-agent objective response and SD rates.