Pentostatin: an adenosine deaminase inhibitor for the treatment of hairy cell leukemia

OBJECTIVE: To review the pharmacology, pharmacokinetics, adverse effects, and various dosage regimens of pentostatin, and to evaluate the role of pentostatin in the treatment of hairy cell leukemia (HCL). DATA IDENTIFICATION: Articles were identified via an English-language literature search of MEDLINE (1966-91) and an extensive search of bibliographies from identified articles. STUDY SELECTION: Human clinical trials and case reports were selected for evaluation. DATA EXTRACTION: The literature was assessed for quality, methodology, and outcome information. DATA SYNTHESIS: At dosages of 4 mg/m2 administered every other week for 6-9 months, pentostatin has been shown to successfully induce a complete response in 58-90 percent of patients and to produce a partial response in up to 30 percent of patients with HCL. The median time to achieve a response is 4.7 months. Long-term remissions of at least 14 months' duration have occurred in some patients. Compared with interferon alfa alone, total response rates are not significantly different when pentostatin and interferon alfa are used in combination. When dosed appropriately, pentostatin is generally well tolerated. Common adverse effects include nausea, vomiting, myelosuppression, fever, and infection. CONCLUSIONS: Pentostatin is a purine analog that inhibits adenosine deaminase, a key enzyme necessary for purine salvage. Pentostatin has received labeling approval for the treatment of HCL refractory to a minimum of three to six months of treatment with interferon alfa. Based on current data, pentostatin will be a useful addition to the therapeutic agents presently available to patients with HCL. Ongoing trials are evaluating the effectiveness of pentostatin as first-line therapy for patients with HCL.