Treatment of relapsed chronic lymphocytic leukemia by 72-hour continuous infusion or 1-hour bolus infusion of flavopiridol: Results from cancer and leukemia group B study 19805

John C. Byrd, Bercedis L. Peterson, Janice Gabrilove, Olatoyosi M. Odenike, Michael R. Grever, Kanti Rai, Richard A. Larson

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118 Scopus citations

Abstract

Purpose: Flavopiridol has in vitro activity in chronic lymphocytic leukemia (CLL) and promotes apoptosis independent of p53 function or prior fludarabine exposure. We sought to determine if flavopiridol has activity in previously treated CLL using two schedules of administration. Patients and Methods: Patients with previously treated CLL were enrolled in two sequentially done phase II studies. Patients in the first trial received flavopiridol (50 mg/m2/d) as a continuous infusion (CI) for 72 hours every 2 weeks. Patients in the second trial received flavopiridol 50 mg/m2 as a 1-hour bolus (IVB) daily for 3 days repeated every 3 weeks. Patients received up to 12 (CI cohort) or 8 (IVB cohort) cycles of therapy. Results: Fifteen patients were enrolled in the 72-hour CI phase II trial; 6 (40%) had intermediate-risk (Rai stage I or II) and 9 (60%) had high-risk (Rai stage III and IV) stages. No responses were noted in this group; 27% had stable disease and 73% had progressive disease. Thirty-six patients were enrolled in the second IVB trial, with 13 (36%) having intermediate and 23 (64%) having high-risk disease. Four patients (11%) had partial responses, 19 (53%) had stable disease, and 13 (36%) had progressive disease. The progression-free survival for responders in the IVB trial was 3, 3,9, and 19 months. The median progression-free survival was 2 months [95% confidence interval (95% CI), 1.8-3.8] for patients in the CI trial and 3 months (95% CI, 2.5-7.4) for the IVB trial. The median overall survival was 27 months (95% CI, 20-42) for the CI trial and 24 months (95% CI, 18-31) for the IVB trial. Toxicity was manageable and included mainly myelosuppression, infections, diarrhea, and fatigue. Conclusions: Flavopiridol has modest, schedule-dependent clinical activity in relapsed CLL and warrants future investigation utilizing alternative schedules of administration.

Original languageEnglish
Pages (from-to)4176-4181
Number of pages6
JournalClinical Cancer Research
Volume11
Issue number11
DOIs
StatePublished - 1 Jun 2005

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