Phase I-II evaluation of intra-arterial diaziquone for recurrent malignant astrocytomas

Cancer Treat Rep. 1986 Mar;70(3):353-7.

Abstract

Diaziquone (AZQ) is a lypophilic alkylating agent that crosses the blood-brain barrier and has shown broad activity in animal tumor models. Five of 12 patients with malignant astrocytoma treated with iv AZQ had clinical and/or radiographic improvement (Schold, Neurology 34:615, 1984). Intra-arterial administration of AZQ to patients with brain tumors should produce higher peak levels of drug in the tumor and should reduce systemic toxicity. Twenty-one patients with astrocytoma (grade II, four; grade III, 11; and grade IV, six), in all of whom irradiation and intra-arterial carmustine chemotherapy failed, received intra-arterial AZQ as a single dose every 28 days. Two of 20 evaluable patients experienced partial responses of 5 and 8+ months, respectively. Four patients had disease stabilization of 3, 4, 5, and 8 months' duration, respectively, and one of these patients had tumor shrinkage (partial response) after seven courses of AZQ. The initial dose in the first three patients was 10 mg/m2, and doses in subsequent groups of three patients were begun at increases of 5 mg/m2. The within-group dose escalation was 5 mg/m2 per course if there was no hematologic toxicity. Dose-limiting toxicity was myelosuppression, which occurred at doses greater than 15 mg/m2. The maximum tolerated dose was 25 mg/m2. Intra-arterial AZQ appears to be of marginal effectiveness in patients refractory to carmustine and offers no advantage over iv AZQ in efficacy or toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / therapeutic use*
  • Astrocytoma / drug therapy*
  • Aziridines / adverse effects
  • Aziridines / metabolism
  • Aziridines / therapeutic use*
  • Azirines / therapeutic use*
  • Benzoquinones*
  • Bone Marrow / drug effects
  • Brain Neoplasms / drug therapy*
  • Carmustine / therapeutic use
  • Drug Evaluation
  • Eye / drug effects
  • Female
  • Glioblastoma / drug therapy*
  • Humans
  • Infusions, Intra-Arterial
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*

Substances

  • Antineoplastic Agents
  • Aziridines
  • Azirines
  • Benzoquinones
  • diaziquone
  • Carmustine