Phase I-II study of piperazinedione in adults with solid tumors and acute leukemia.
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.
D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects; D002986:Clinical Trials as Topic; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D009369:Neoplasms / Q000188:drug therapy*; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity
D000903:Antibiotics, Antineoplastic; D010879:Piperazines; C003905:3,6-bis(5-chloro-2-piperidyl)-2,5-piperazinedione