A phase I/II study of 24 hour intravenous AZQ in recurrent primary brain tumors.
This study was undertaken to determine the maximum tolerated dose of aziridinylbenzoquinone (AZQ) given as a 24-hour intravenous infusion every 21-28 days. Thirty-four patients with recurrent or progressive gliomas received AZQ at a dose of 25, 30, 35, 40, or 45 mg/m2. At a dose of 45 mg/m2, leukopenia and thrombocytopenia of grade 3 or greater was observed in 42% and 25% of patients respectively; no patient required transfusion or antibiotics for fever. For administration of AZQ at a 24-hour intravenous infusion, we recommend a starting dose of 40 mg/m2 for patients without previous exposure to cytotoxic agents, and 35 mg/m2 for patients treated with such agents. In 14 patients with glioblastoma, tumor regression was observed in 1 patient (14%) and stabilization of disease was demonstrated in 7 patients (50%). In 17 patients with anaplastic astrocytomas there were no responses, but 8 patients (47%) stabilized. Of two patients with an oligodendroglioma, one continues without progression at 34 weeks after initial response. One patient with malignant ependymoma stabilized and had not progressed at 39 weeks. The median time to tumor progression in patients who stabilized and responded was 18 weeks for those with glioblastoma multiforme and 16 weeks in those with anaplastic astrocytomas.
Chamberlain
M C
MC
Brain Tumor Research Center, University of California Medical School, San Francisco 94143.
Prados
M D
MD
Silver
P
P
Levin
V A
VA
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001388:Aziridines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001389:Azirines / Q000627:therapeutic use*; D016227:Benzoquinones; D001932:Brain Neoplasms / Q000188:drug therapy*; D004341:Drug Evaluation; D006801:Humans; D007262:Infusions, Intravenous; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*
D000970:Antineoplastic Agents; D001388:Aziridines; D001389:Azirines; D016227:Benzoquinones; C029108:diaziquone