PHASE-I STUDY OF AZIRIDINYLBENZOQUINONE (AZQ, NSC-182986) IN CHILDREN WITH CANCER

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (2) , 831-835
Abstract
Aziridinylbenzoquinone can penetrate the CNS and it has demonstrated antitumoral activity experimentally. A Phase I trial of aziridinylbenzoquinone was conducted in 60 children with advanced cancer who were refractory to conventional therapy. The drug was given by slow i.v. push daily for 5 days every 3-4 wk. The dose ranged from 6-12 mg/sq m daily for 5 days in patients with solid tumors and leukemia, and in patients with leukemia, 20, 25 and 30 mg/sq m daily for 5 days. Myelosuppression was the dose-limiting side effect. There may be cumulative toxicity with prolonged thromobocytopenia. Other side effects were mild nausea, vomiting and mucositis. Elevations in liver enzymes and bilirubin were transient and dose dependent. Partial responses lasting 3 wk to 6 mo. were seen in the 4 patients with Hodgkin''s disease, and in a child with a metastatic spinal cord ependymoma. Of the 15 patients with acute nonlymphoblastic leukemia treated at doses .gtoreq. mg/sq m per day for 5 days there was 1 early death and there were 2 M1 (.ltoreq. 5% blasts with normal cellularity), 3 M2A (6 to 15% blasts), and 2 M2B (16-39% blasts) bone marrow responses lasting 1-3.5 mo. Aziridinylbenzoquinone demonstrated activity against acute nonlymphocytic leukemia with maximal tolerated doses of 30 mg/sq m daily for 5 days. Its effect in Hodgkin''s disease is encouraging; however, further study will be required to determine its efficacy in CNS cancers. Recommended doses for Phase II studies, using daily schedule for 5 days in children with solid tumors, is 9 mg/sq m, and in children with leukemia, it is 25 mg/sq m.