title: Phase I-II evaluation of intra-arterial diaziquone for recurrent malignant astrocytomas.
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.
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D001254:Astrocytoma / Q000188:drug therapy*; D001388:Aziridines / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D001389:Azirines / Q000627:therapeutic use*; D016227:Benzoquinones; D001853:Bone Marrow / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy*; D002330:Carmustine / Q000627:therapeutic use; D004341:Drug Evaluation; D005123:Eye / Q000187:drug effects; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D001388:Aziridines; D001389:Azirines; D016227:Benzoquinones; C029108:diaziquone; D002330:Carmustine