Phase II study of acivicin in patients with recurrent high grade astrocytoma

Acivicin, an antimetabolite which inhibits enzymes necessary for glutamine utilization, was administered to 16 patients with recurrent high grade astrocytoma. The dose was 12 mg/m(2)/day intravenously over 30 min, daily for 5 days to be repeated every 3 weeks. All patients had previously received cranial irradiation. There were no objective responders, two patients remained stable, two were not evaluable for response and the other 12 progressed on treatment. The median survival of the patients was 128 days. The major toxicity was reversible neurological toxicity, with episodes of WHO grade 3 symptoms in two patients, grade 2 in 19 and grade 1 in six patients. Non-neurological toxicities were infrequent with two patients with grade 2 vomiting and two patients developing infections on treatment, although no severe myelosuppression occurred. Three patients developed mild rashes. The lack of activity and the neurological toxicity makes a daily for 5 days schedule of acivicin unsuitable for further study in central nervous system tumours.