A study of a different dose-intense infusion schedule of phenylacetate in patients with recurrent primary brain tumors

• Published in: Investigational new drugs 2003-11, Vol.21 (4), p.429-433
• Main Authors: Chang, Susan M., Kuhn, John G., Ian Robins, H., Clifford Schold, S., Spence, Alexander M., Berger, Mitchel S., Mehta, Minesh P., Pollack, Ian, Gilbert, Mark, Prados, Michael D.
• Format: Article
• Language: English
• Subjects: Brain cancer; Chemotherapy; Confidence intervals; Drug dosages; Metabolism; Neurotoxicity; Patients; Pharmacokinetics; Plasma; Radiation therapy; Schedules; Toxicity; Tumors
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1023/A:1026299118067

To compare two different infusion schedules of phenylacetate (PA) in patients with primary brain tumors and to assess the feasibility of the administration in a multi-institutional setting. Adult patients with recurrent primary brain tumors were treated with PA on two different schedules. The first schedule (I) consisted of a 2-week continuous, intravenous infusion followed by a 2-week rest period (14 days on, 14 days off) at a dose of 400 mg/kg/day based on ideal body weight. This was repeated once and the 8-week period defined as a cycle. The second schedule (II) consisted of a 12-day continuous infusion at a dose of 400 mg/kg/day based on IBW with a 2-day rest period. This was repeated four times for a duration of 8 weeks which defined one cycle of therapy. Cycles were repeated until tumor progression, unacceptable toxicity, or a delay of more than 28 days from the last day of the preceding infusion. Tumor response was assessed every 8 weeks. The National Cancer Institute toxicity criteria were used to assess toxicity. Dose adjustments were specified for toxicities. Plasma concentrations achieved during the patients' first cycle of therapy were assessed. The clinical results of the phase II study of patients treated on schedule I were previously reported [8]. Of the nine eligible patients treated on schedule II, seven were assessable for radiographic response. There were no objective responses. One patient had stable disease and six had progressive disease. The median survival was 9 months (95% confidence intervals of 3-12 months). The steady state plasma concentrations of PA and phenylacetylglutamine were comparatively the same between the two dosing schedules. However a 1.7-fold greater amount of PA was delivered by schedule II. The infusions were well tolerated. Despite the feasibility of administering this agent in an outpatient setting, there were no responses seen with the more intensive schedule of PA.