title: Pentostatin (Nipent) in T-cell malignancies. Leukemia Cooperative Group and the European Organization for Research and Treatment of Cancer.
abstract: Within this phase II trial of the European Organization for Research and Treatment of Cancer, we have investigated the safety and efficacy of pentostatin (Nipent; SuperGen, San Ramon, CA) in refractory lymphoid malignancies. Pentostatin was administered at a dosage of 4 mg/m2 every week for the first 3 weeks, then every 14 days, followed by maintenance therapy of 4 mg/m2 monthly for a maximum of 6 months. We have previously reported the results in T- and B-cell prolymphocytic leukemia, B-cell chronic lymphocytic leukemia, and hairy cell leukemia This report focuses on the outcome in T-cell malignancies: T-cell chronic lymphocytic leukemia, Sézary syndrome, mycosis fungoides, and T-zone lymphoma. Of 92 patients with these diagnoses enrolled, 76 were evaluable for response and toxicity, ie, 25 of 28 with T-cell chronic lymphocytic leukemia, 21 of 26 with Sézary syndrome, 22 of 26 with mycosis fungoides, and eight of 12 with T-zone lymphoma. All patients had progressive and advanced disease. Sixteen patients (21%) died during the first 9 weeks of treatment: 12 of progressive disease, two of infectious complications thought to be unrelated to treatment, one of myocardial infarction, and one of renal failure related to administration of intravenous contrast. Major toxicity (grades 3 and 4) included infection in 10.5% of patients, nausea/vomiting in 5%, and hepatotoxicity in 3%. One patient (1.3%) achieved a complete remission and 15 (19.7%) a partial remission. Better results were achieved in patients with Sézary syndrome or mycosis fungoides (complete remission + partial remission = 33.4% and 22.7%, respectively) than in patients with T-cell chronic lymphocytic leukemia (8%) or T-zone lymphoma (25%). We conclude that pentostatin is active in low-grade T-cell malignancies. Toxicities are mild to moderate at the dose schedule administered. Severe hematologic toxicity has not been observed. The efficacy at the present dose level is moderate. A higher dose might be necessary for some T-cell malignancies.
authors.affiliation: Department of Medicine, University of Heidelberg, Germany.
authors.forename: A D
authors.initials: AD
authors.lastname: Ho
authors.forename: S
authors.initials: S
authors.lastname: Suciu
authors.forename: P
authors.initials: P
authors.lastname: Stryckmans
authors.forename: F
authors.initials: F
authors.lastname: De Cataldo
authors.forename: R
authors.initials: R
authors.lastname: Willemze
authors.forename: J
authors.initials: J
authors.lastname: Thaler
authors.forename: M
authors.initials: M
authors.lastname: Peetermans
authors.forename: H
authors.initials: H
authors.lastname: Döhner
authors.forename: G
authors.initials: G
authors.lastname: Solbu
authors.forename: M
authors.initials: M
authors.lastname: Dardenne
authors.forename: R
authors.initials: R
authors.lastname: Zittoun
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002423:Cause of Death; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007943:Leukemia, Hairy Cell / Q000188:drug therapy; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy; D015463:Leukemia, Prolymphocytic / Q000188:drug therapy; D015458:Leukemia, T-Cell / Q000188:drug therapy*; D016399:Lymphoma, T-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000188:drug therapy; D015649:Pentostatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012074:Remission Induction; D012751:Sezary Syndrome / Q000188:drug therapy; D012878:Skin Neoplasms / Q000188:drug therapy; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D007166:Immunosuppressive Agents; D015649:Pentostatin