Infusion carboplatin treatment of relapsed and refractory acute leukemia: evidence of efficacy with minimal extramedullary toxicity at intermediate doses

J Clin Oncol. 1989 Feb;7(2):173-8. doi: 10.1200/JCO.1989.7.2.173.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Carboplatin
  • Diarrhea / chemically induced
  • Drug Administration Schedule
  • Drug Evaluation
  • Female
  • Hearing Loss, High-Frequency / chemically induced
  • Hematopoiesis / drug effects
  • Humans
  • Infusions, Intravenous
  • Leukemia, Myeloid, Acute / drug therapy*
  • Male
  • Middle Aged
  • Organoplatinum Compounds / administration & dosage*
  • Organoplatinum Compounds / adverse effects
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Recurrence
  • Vomiting / chemically induced

Substances

  • Antineoplastic Agents
  • Organoplatinum Compounds
  • Carboplatin