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Flavopiridol in Untreated or Relapsed Mantle-Cell Lymphoma: Results of a Phase II Study of the National Cancer Institute of Canada Clinical Trials Group

C. Tom Kouroukis, Andrew Belch, Michael Crump, Elizabeth Eisenhauer, Randy D. Gascoyne, Ralph Meyer, Reinhard Lohmann, Pedro Lopez, Jean Powers, Robert Turner, Joseph M. Connors

From the Hamilton Regional Cancer Centre, Hamilton; Princess Margaret Hospital, Toronto; National Cancer Institute of Canada, Clinical Trials Group, Queen’s University, Kingston; London Regional Cancer Centre, London; Northeastern Ontario Regional Cancer Centre, Sudbury, Ontario; Cross Cancer Institute, Edmonton, Alberta; and British Columbia Cancer Agency, Vancouver Cancer Centre, Vancouver, British Columbia, Canada.

Address reprint requests to C. Tom Kouroukis, MD, Hematology-Oncology, Hamilton Regional Cancer Centre, 699 Concession Street, Hamilton, Ontario L8V 5C2 Canada; email: tom.kouroukis{at}hrcc.on.ca.

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.

Supported by a grant from the National Cancer Institute of Canada.

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