Cladribine for the treatment of hematologic malignancies
Baltz, J.K.; Montello, M.J.
Clinical Pharmacy 12(11): 805
1993
ISSN/ISBN: 0278-2677 PMID: 7903917 Document Number: 407857
The mechanism of action, pharmacokinetics, efficacy, adverse effects, storage, dosage and administration, and cost of cladribine are reviewed. Cladribine (2-chloro-2'-deoxyadenosine) is a synthetic purine nucleoside developed for the treatment of hematologic malignancies. It appears that cladribine interferes with lymphocyte proliferation by inhibiting DNA repair. The pharmacokinetics of cladribine best fit a two-compartment, first-order-elimination model. Of the conditions that have been treated with cladribine, hairy cell leukemia (HCL) has shown the most dramatic response. Overall response rates in clinical studies have ranged from 80% to 100%, with a large majority of these being complete remissions; median durations of responses have ranged from about 9 to 16 months. Other conditions that have responded to cladribine are chronic lymphocytic leukemia (CLL), acute leukemia, chronic myeloid leukemia, low-grade lymphomas, Waldenstrom's macroglobulinemia, and cutaneous T-cell lymphoma. The drug is inactive against solid tumors. The principal dose-limiting adverse effect of cladribine is bone marrow suppression; fever, immunosuppression, renal and neurologic effects, and local skin reactions have also been reported. The drug is typically administered as an extended continuous i.v. infusion. The usual dosage for treatment HCL is 0.1 mg/kg/day for seven days. The estimated cost of cladribine for treating HCL is 0.1 mg/kg/day for seven days. The estimated cost of cladribine for treating an average patient with HCL is 3500. Cladribine has shown efficacy against a variety of hematologic malignancies, notably HCL and CLL.