Phase II trials of pentostatin (Nipent) in hairy cell leukemia.
Hairy cell leukemia (HCL) is a chronic lymphoproliferative disease of B-cell origin manifested by pancytopenia and splenomegaly. Before 1980 the only effective treatment for HCL was splenectomy, which resolved the cytopenia but did not eliminate the disease from the bone marrow. In addition, the majority of patients progressed after splenectomy and required further treatment. Pentostatin (Nipent; SuperGen, San Ramon, CA) is a purine antimetabolite that was found in phase I studies to induce profound lymphocytopenia Although in vitro studies suggested that T lymphocytes were most sensitive to pentostatin, patients with B-cell chronic lymphatic leukemia and low-grade non-Hodgkin's lymphoma responded to treatment in the initial phase I trials. Due to evidence that the drug was effective in lymphoproliferative disease, patients with HCL were treated with pentostatin. The promising initial results led to phase II studies in both untreated and previously treated patients. These studies demonstrated that pentostatin was highly effective as a single agent, with complete responses seen in 60% to 90% of patients. These responses were durable without maintenance chemotherapy and were seen in patients previously treated with interferon or chemotherapy. Toxicity was usually mild, with nausea and skin rashes predominating. When seen, infections resulting from neutropenia occurred early in treatment. The high response rates and low toxicity suggest that pentostatin should be considered as one of the standard treatments for HCL.
Kraut
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Division of Hematology and Oncology, Ohio State University, Columbus 43210, USA.
D058892:Adenosine Deaminase Inhibitors; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D018450:Disease Progression; D003875:Drug Eruptions / Q000209:etiology; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005076:Exanthema / Q000139:chemically induced; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015448:Leukemia, B-Cell / Q000188:drug therapy; D007943:Leukemia, Hairy Cell / Q000188:drug therapy*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy; D009325:Nausea / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D010198:Pancytopenia / Q000188:drug therapy; D015649:Pentostatin / Q000009:adverse effects / Q000627:therapeutic use*; D012074:Remission Induction; D013163:Splenomegaly / Q000188:drug therapy / Q000601:surgery
D058892:Adenosine Deaminase Inhibitors; D000903:Antibiotics, Antineoplastic; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D015649:Pentostatin