Phase I-II study of piperazinedione in adults with solid tumors and acute leukemia

Cancer Treat Rep. 1979 Jun;63(6):939-43.

Abstract

Piperazinedione was administered to 79 patients with solid tumors on an intermittent schedule with single doses of 1.5-36 mg/m2. Courses were usually repeated at 4-week intervals. Twenty-five patients with leukemia were treated at doses of 18-36 mg/m2 (occasionally for 2 successive days) every 1-4 weeks. Of 48 evaluable patients with malignant melanoma, three (6%) achieved partial remission and nine (20%) had stable disease. Eight of 17 (47%) patients with adenocarcinomas and one of two (50%) patients with lymphomas also had stable disease. Six of 14 (43%) patients with acute myelogenous leukemia showed hematologic improvement, as did one of 11 (9%) patients with blast cell crisis of chronic myelogenous leukemia. The principal toxic effect was myelosuppression, which occurred in 69% of the patients with solid tumors. Profound bone marrow aplasia occurred in 19% of the patients, resulting in six deaths (8%). Risk factors for marrow aplasia included extensive prior therapy, prior nitrosoureas, cumulative toxicity from piperazinedione, and abnormal liver function tests. The recommended doses for further studies are 9 mg/m2 for patients with risk factors for marrow aplasia, 12 mg/m2 for patients with prior therapy, 15 mg/m2 for previously untreated patients, and 24-36 mg/m2 for patients with acute leukemia.

Publication types

  • Clinical Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antibiotics, Antineoplastic / therapeutic use*
  • Bone Marrow / drug effects
  • Clinical Trials as Topic
  • Drug Evaluation
  • Female
  • Humans
  • Leukemia, Myeloid / drug therapy*
  • Leukemia, Myeloid, Acute / drug therapy*
  • Male
  • Melanoma / drug therapy*
  • Neoplasms / drug therapy*
  • Piperazines / administration & dosage
  • Piperazines / therapeutic use*
  • Piperazines / toxicity

Substances

  • Antibiotics, Antineoplastic
  • Piperazines
  • 3,6-bis(5-chloro-2-piperidyl)-2,5-piperazinedione