title: Concomitant administration of chlorambucil limits dose intensity of fludarabine in previously treated patients with chronic lymphocytic leukemia.
abstract: Fifteen patients with chronic lymphocytic leukemia (CLL) were treated in a phase I-II study of chlorambucil with an escalating dose of fludarabine. The study was designed to identify a maximum tolerated dose (MTD) of fludarabine given in conjunction with a constant dose of chlorambucil. Patients were eligible for study if they had Rai intermediate or high-risk disease which had relapsed from or was refractory to conventional treatment. The initial cohort of patients received fludarabine 10 mg/m2/d days 1-5 and chlorambucil 20 mg/m2 days 1 and 15. Cycles were repeated every 28 days. Unacceptable toxicity was encountered in this cohort. The protocol was then modified to give chlorambucil 20 mg/m2 on day 1 (only). At this chlorambucil dose, cohorts of three patients were treated with fludarabine 10, 15, and 20 mg/m2/d x 5 days. The predominant toxicity was thrombocytopenia with 73% experiencing grade > or = 3 toxicity. The dose-limiting non-hematologic toxicity was infection. We identified an MTD of fludarabine of 15 mg/m2/d x 5 days when given with chlorambucil 20 mg/m2 for this group of patients. One patient achieved a CR and three patients achieved a PR for a total response rate of 27%. We conclude that concomitant administration of chlorambucil limits the dose intensity of fludarabine which can be administered to previously treated patients with CLL.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
authors.forename: M
authors.initials: M
authors.lastname: Weiss
authors.forename: T
authors.initials: T
authors.lastname: Spiess
authors.forename: E
authors.initials: E
authors.lastname: Berman
authors.forename: S
authors.initials: S
authors.lastname: Kempin
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000633:toxicity*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D002699:Chlorambucil / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010976:Platelet Count / Q000187:drug effects; D012008:Recurrence; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D002699:Chlorambucil; D014740:Vidarabine; C024352:fludarabine