The role of pentostatin (2'-deoxycoformycin, dCF) in the management of lymphoproliferative malignancies.
Laboratory and clinical data relating to the use of 2'-deoxycoformycin in human disease are reviewed. Pentostatin is an inhibitor of adenosine deaminase, an enzyme that is important for purine metabolism, but more than one mechanism may be involved in its cytotoxic action. Early studies with dCF employed large doses and for the most part were conducted in patients with acute lymphocytic leukaemia: responses were brief and relatively few, and severe renal, hepatic, and central nervous system toxicity were encountered, leading to temporary abandonment of clinical trials. More recently, it has been shown that dCF is effective in much smaller doses, with considerably less toxicity. It has proved to be more effective in low-grade lymphoid malignancies (chronic leukaemias, indolent lymphomas) than in more undifferentiated neoplasms (acute leukaemias, lymphoblastic and immunoblastic lymphomas), and is outstandingly effective in hairy cell leukaemia, both as initial therapy and after failure of splenectomy and interferon. Pentostatin is profoundly immunosuppressive: generally this is considered a disadvantage but its potential therapeutic exploitation merits investigation. Despite extensive knowledge of its biochemical effects, the optimal dose regimen of dCF and the value of combining it with purine antagonists remain to be defined.
Spiers
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Division of Oncology, Albany Medical College, New York 12208.
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003070:Coformycin / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000188:drug therapy*; D015649:Pentostatin; D012263:Ribonucleosides / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D012263:Ribonucleosides; D003070:Coformycin; D015649:Pentostatin