Flavopiridol in untreated or relapsed mantle-cell lymphoma: results of a phase II study of the National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: To determine the response rate and toxicity of flavopiridol in patients with previously untreated or relapsed mantle-cell lymphoma. PATIENTS AND METHODS: Adult patients with previously untreated or in first or second relapse of previously responsive mantle-cell lymphoma were given flavopiridol 50 mg/m2/d by intravenous bolus for 3 consecutive days every 21 days with antidiarrheal prophylaxis. Flavopiridol was continued until disease progression, unacceptable toxicity, or stable disease for four cycles. Disease was reassessed every two cycles. RESULTS: From 33 registered patients, 30 were eligible after pathology review, 30 were assessable for toxicity, and 28 were assessable for response. A median of four cycles of treatment was administered; 90% of patients received at least 90% of planned dose-intensity. No complete responses were seen; three patients had a partial response (11%), 20 patients had stable disease (71%), and five patients had progressive disease (18%). The median duration of response was 3.3 months (range, 2.8 to 13.2 months). The most common toxicities were diarrhea (97%), fatigue (73%), nausea (47%), and vomiting (27%). At least one nonhematologic grade 3 or 4 toxicity was seen in 14 patients (47%). Hematologic toxicity was modest. CONCLUSIONS: Flavopiridol given as a daily bolus for 3 consecutive days every 3 weeks has modest activity as a single agent for mantle-cell lymphoma. The number of stable and partial responses that was seen indicates that it is biologically active and may delay progression. Future studies in mantle-cell lymphoma should test this agent with other active agents and using different schedules.