This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Byrd, J. C. Search for Related Content PubMed PubMed Citation Articles by Byrd, J. C.

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

Authors' Affiliations: ¹ Division of Hematology-Oncology, Department of Medicine, The Ohio State University, Columbus, Ohio; ² Cancer and Leukemia Group B, Statistical Center, Duke University Medical Center, Durham, North Carolina; ³ Division of Neoplastic Diseases, Mount Sinai Hospital, New York, New York; ⁴ Department of Medicine, The University of Chicago, Chicago, Illinois; and ⁵ Divisions of Hematology and Oncology, Long Island Jewish Medical Center, New Hyde Park, New York

Requests for reprints: John C. Byrd, Division of Hematology-Oncology, The Ohio State University, Starling Loving Hall, Room 302, Columbus, OH 43210. Phone: 614-293-9321; E-mail: byrd-3{at}medctr.osu.edu.

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.

Key Words: Leukemias and lymphonas • Hematologic, other • CDKs and CDK inhibitors

This article has been cited by other articles:

				E. Weingrill, A. Wolfler, D. Strunk, W. Linkesch, H. Sill, and P. M. Liebmann Roscovitine in B-chronic lymphocytic leukemia cells: high apoptosis-inducing efficacy and synergism with alemtuzumab independent of the patients' pretreatment status Haematologica, September 1, 2007; 92(9): 1286 - 1288. [Abstract] [Full Text] [PDF]

				J. E. Karp, B. D. Smith, M. J. Levis, S. D. Gore, J. Greer, C. Hattenburg, J. Briel, R. J. Jones, J. J. Wright, and A. D. Colevas Sequential Flavopiridol, Cytosine Arabinoside, and Mitoxantrone: A Phase II Trial in Adults with Poor-Risk Acute Myelogenous Leukemia Clin. Cancer Res., August 1, 2007; 13(15): 4467 - 4473. [Abstract] [Full Text] [PDF]

				J. C. Byrd, T. S. Lin, J. T. Dalton, D. Wu, M. A. Phelps, B. Fischer, M. Moran, K. A. Blum, B. Rovin, M. Brooker-McEldowney, et al. Flavopiridol administered using a pharmacologically derived schedule is associated with marked clinical efficacy in refractory, genetically high-risk chronic lymphocytic leukemia Blood, January 15, 2007; 109(2): 399 - 404. [Abstract] [Full Text] [PDF]

				O. A. O'Connor Mantle Cell Lymphoma: Identifying Novel Molecular Targets in Growth and Survival Pathways Hematology, January 1, 2007; 2007(1): 270 - 276. [Abstract] [Full Text] [PDF]

				E. B. Sambol, G. Ambrosini, R. C. Geha, P. T. Kennealey, P. DeCarolis, R. O'Connor, Y. V. Wu, M. Motwani, J.-H. Chen, G. K. Schwartz, et al. Flavopiridol Targets c-KIT Transcription and Induces Apoptosis in Gastrointestinal Stromal Tumor Cells Cancer Res., June 1, 2006; 66(11): 5858 - 5866. [Abstract] [Full Text] [PDF]

				G. I. Shapiro Cyclin-Dependent Kinase Pathways As Targets for Cancer Treatment J. Clin. Oncol., April 10, 2006; 24(11): 1770 - 1783. [Abstract] [Full Text] [PDF]

				J. E. Karp, A. Passaniti, I. Gojo, S. Kaufmann, K. Bible, T. S. Garimella, J. Greer, J. Briel, B. D. Smith, S. D. Gore, et al. Phase I and Pharmacokinetic Study of Flavopiridol followed by 1-{beta}-D-Arabinofuranosylcytosine and Mitoxantrone in Relapsed and Refractory Adult Acute Leukemias Clin. Cancer Res., December 1, 2005; 11(23): 8403 - 8412. [Abstract] [Full Text] [PDF]

				E. Montserrat Fighting CLL cells: deciphering the enemy Blood, October 1, 2005; 106(7): 2226 - 2226. [Full Text] [PDF]

				J. G. Gribben Salvage Therapy for CLL and the Role of Stem Cell Transplantation Hematology, January 1, 2005; 2005(1): 292 - 298. [Abstract] [Full Text] [PDF]