Clinical and pharmacokinetic study of clofarabine in chronic lymphocytic leukemia: strategy for treatment.

Clinical and pharmacokinetic study of clofarabine in chronic lymphocytic leukemia: strategy for treatment. Research Abstract Details 

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Clinical and pharmacokinetic study of clofarabine in chronic lymphocytic leukemia: strategy for treatment. Abstract Text:

Varsha Gandhi,William Plunkett,Peter L Bonate,Min Du,Billie Nowak,Susan Lerner,Michael J Keating,

PURPOSE: Based on its mechanistic similarity to fludarabine and cladribine and the success of these analogues for treatment of chronic lymphocytic leukemia (CLL), we hypothesized that clofarabine would be effective for indolent leukemias. The present study was conducted to determine the efficacy and cellular pharmacology during clinical trials of single-agent clofarabine in CLL. EXPERIMENTAL DESIGN: Previously treated patients with relapsed/refractory CLL were eligible for this study. Clofarabine was infused over 1 hour daily for 5 days. Most patients received 3 or 4 mg/m2/d x 5 days, whereas the other two were treated with 15 mg/m2/d x 5 days. Clinical outcome and associated pharmacologic end points were assessed. RESULTS: Myelosuppression limited the maximum tolerated dose of clofarabine to 3 mg/m2/d on this schedule. Cellular pharmacokinetic studies showed a median clofarabine triphosphate concentration in CLL lymphocytes of 1.5 micromol/L (range, 0.2-2.3 micromol/L; n = 9). In the majority of cases, >50% of the analogue triphosphate was present 24 hours after infusion, indicating prolonged retention of the triphosphate in CLL cells. Although cytoreduction was observed, no patients achieved a response. In vitro clofarabine incubation of leukemic lymphocytes from 29 CLL patients showed that clofarabine monophosphate accumulated to a higher concentration compared with the triphosphate. Nonetheless, the triphosphate increased in a dose-dependent fashion and upon successive clofarabine infusions, suggesting benefit from greater doses given at less frequent intervals. CONCLUSION: Levels of clofarabine triphosphate at higher doses and prolonged maintenance of clofarabine triphosphate in leukemic lymphocytes provide a rationale to treat CLL in a weekly clofarabine schedule.

Clinical and pharmacokinetic study of clofarabine in chronic lymphocytic leukemia: strategy for treatment. Publishing Authors By Initials

V Gandhi,W Plunkett,PL Bonate,M Du,B Nowak,S Lerner,MJ Keating,

For similar diagnosis: prognosis: treatment outcome research abstracts see: diagnosis: prognosis: treatment outcome research

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Clinical and pharmacokinetic study of clofarabine in chronic lymphocytic leukemia: strategy for treatment. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Clinical cancer research : an official journal of

VOLUME: 12

Page Numbers: 4011-7

Journal Abbreviation: Clin. Cancer Res.

ISSN: 1078-0432

DAY: 1

MONTH: Jul

YEAR: 2006

Clinical and pharmacokinetic study of clofarabine in chronic lymphocytic leukemia: strategy for treatment. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9502500

Clinical and pharmacokinetic study of clofarabine in chronic lymphocytic leukemia: strategy for treatment. Keywords Mesh Terms:

KEYWORDS: Treatment Outcome

MESH TERMS: drug effects

Chemical & Substance for Abstract: Clinical and pharmacokinetic study of clofarabine in chronic lymphocytic leukemia: strategy for treatment. Information

Substance Name: clofarabine

Registry Number: 123318-82-1

Grant and Affiliation Information for Clinical and pharmacokinetic study of clofarabine in chronic lymphocytic leukemia: strategy for treatment.

AFFILIATION: Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. vgandhi@mdanderson.org

Country: United States

AGENCY: United States NCI

GRANT: CA81534

ACRONYM: CA

MEDLINETA: Clin Cancer Res

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