title: Infusion carboplatin treatment of relapsed and refractory acute leukemia: evidence of efficacy with minimal extramedullary toxicity at intermediate doses.
abstract: Carboplatin (CBDCA) is a second-generation platinum analog with prominent myelotoxicity and modest extramedullary toxicity. We performed a phase I study of CBDCA in adult patients with relapsed acute leukemia. Therapy was administered as a five-day continuous infusion. The initial dose of 875 mg/m2 over five days was escalated in 15% increments to a final dose of 2,100 mg/m2 over five days. Twenty-eight patients received 35 induction courses of CBDCA, including two patients who achieved a complete remission (CR) following the first course, and received a second induction course at the time of relapse. Therapy was well tolerated. No grade 3 or 4 extramedullary toxicity was seen. Myelosuppression was regularly observed, with prolonged myelosuppression at 2,100 mg/m2 over five days being the indication to cease dose escalation. Eight of 28 patients (28.5%) responded to CBDCA therapy (six CR, two partial remission [PR]) or ten of 30 initial induction courses (33.3%). Continuous-infusion CBDCA has an advantage over other therapy for acute leukemia because of its highly selective myelotoxicity and minimal gastrointestinal and renal toxicity. A standard phase II study should be undertaken to establish a more accurate response rate.
authors.affiliation: Department of Medicine, University of California, Davis Medical Center, Sacramento.
authors.forename: F J
authors.initials: FJ
authors.lastname: Meyers
authors.forename: J
authors.initials: J
authors.lastname: Welborn
authors.forename: J P
authors.initials: JP
authors.lastname: Lewis
authors.forename: N
authors.initials: N
authors.lastname: Flynn
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D006316:Hearing Loss, High-Frequency / Q000139:chemically induced; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012008:Recurrence; D014839:Vomiting / Q000139:chemically induced
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D016190:Carboplatin