Pentostatin

Pentostatin (2'-deoxycoformycin) was the first purine analog to be tested in clinical trials. This agent inhibits the enzyme adenosine deaminase, and its development was based on the observations that children with severe combined immunodeficiency lack adenosine deaminase and that lymphocytes are rich in the enzyme. Pentostatin at a dose of 4 mg/m2 weekly or every 2 wk induced responses in 5 of 28 patients with advanced CLL refractory to alkylating agents in the initial study by Grever at al. (20). These results were confirmed in a phase II study by the Cancer and Leukemia Group B, in which pentostatin 4 mg/m2 weekly for 3 wk and then every 2 wk produced complete responses in 3% and partial responses in 23% of patients (21).

A common side effect of all nucleoside analogs is immunosuppression; infections occurred in up to one-third of patients treated with pentostatin (22). Myelosuppression, nausea and vomiting, rash, mucositis, and, less commonly, neurotoxicity have also been observed in patients with CLL treated with pentostatin (23,24).

Although single-agent pentostatin appeared to have less activity in CLL than other purine analogs (vide see just above), there is significant interest in using this agent in combination because it is regarded as less myelosuppressive. Two clinical studies evaluating the combination of pentostatin and an alkylating agent recently started; one combines pentostatin and chlorambucil with the support of granulocyte/macrophage colony-stimulating factor (25), and the other is evaluating the efficacy of pentostatin and cyclophosphamide (26). The combination of pentostatin and the monoclonal antibody rituximab is also being evaluated in a phase II multicenter study (27).

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