CLADRIBINE FOR THE TREATMENT OF HEMATOLOGIC MALIGNANCIES

The mechanism of action, pharmacokinetics, efficacy, adverse effects, storage, dosage and administration, and cost of cladribine are reviewe d. Cladribine (2-chloro-2'-deoxyadenosine) is a synthetic purine nucle oside developed for the treatment of hematologic malignancies. It appe ars that cladribine interferes with lymphocyte proliferation by inhibi ting DNA repair. The pharmacokinetics of cladribine best fit a two-com partment, first-order-elimination model. Of the conditions that have b een treated with cladribine, hairy cell leukemia (HCL) has shown the m ost dramatic response. Overall response rates in clinical studies have ranged from 80% to 100%, with a large majority of these being complet e remissions; median durations of responses have ranged from about 9 t o 16 months. Other conditions that have responded to cladribine are ch ronic lymphocytic leukemia (CLL), acute leukemia, chronic myeloid leuk emia, low-grade lymphomas, Waldenstrom's macroglobulinemia, and cutane ous T-cell lymphoma. The drug is inactive against solid tumors. The pr incipal dose-limiting adverse effect of cladribine is bone marrow supp ression; fever, immunosuppression, renal and neurologic effects, and l ocal skin reactions have also been reported. The drug is typically adm inistered as an extended continuous i.v. infusion. The usual dosage fo r 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. Cladribi ne has shown efficacy against a variety of hematologic malignancies, n otably HCL and CLL.