Phase II study of phenylacetate in patients with recurrent malignant glioma: A North American brain tumor consortium report

Purpose: To determine the response rate, time to treatment failure, and tox icity of phenylacetate in patients with recurrent malignant glioma and to i dentify plasma concentrations achieved during repeated continuous infusion of this agent. Patients and Methods: Adult patients with recurrent malignant glioma were t reated with phenylacetate. The schedule consisted of a 2-week continuous, i ntravenous infusion followed by a 2-week rest period (14 days on, 14 days o ff). A starting dose of 400 mg/kg total body weight per day of phenylacetat e was initially used and subsequently changed to 400 mg/kg/d based on ideal body weight. Intrapatient dose escalations were allowed to a maximum of 45 0 mg/kg ideal body weight/d. Tumor response was assessed every 8 weeks. The National Cancer institute common toxicity criteria were used to assess tox icity. Plasma concentrations achieved during the patients' first two 14-day infusions were assessed. Results: Forty-three patients were enrolled between December 1994 and Decem ber 1996. Of these, 40 patients were assessable for toxicity and response t o therapy. Reversible symptoms of fatigue and somnolence were the primary t oxicities, with only mild hematologic toxicity. Thirty (75%) of the 40 pati ents failed treatment within 2 months, seven (17.5%) had stable disease, an d three (7.5%) had a response defined as more than 50% reduction in the tum or Median time to treatment failure was 2 months. Thirty five patients have died, with a median survival of 8 months. Pharmacokinetic data for this do se schedule showed no difference in the mean plasma concentrations of pheny lacetate between weeks 1 and 2 or between weeks 5 and 6. Conclusion: phenylacetate has little activity at this dose schedule in pati ents with recurrent malignant glioma. Further studies with this drug would necessitate an evaluation of a different dose schedule. a 1999 by American Society of Clinical Oncology.