A phase II study of temozolomide plus pegylated interferon alfa-2b for recurrent anaplastic glioma and glioblastoma multiforme

Abstract

1519 Background: Based on prior studies suggesting promise of interferon alfa-2b and temozolomide (TMZ) in relapsed malignant glioma patients, we are testing this combination with a long acting (pegylated) form of interferon alfa-2b (PIFN) prolonging drug exposure and attempting to increase anti-tumor activity. Methods: We are conducting a prospective phase II trial of TMZ plus PIFN in adult patients with recurrent anaplastic glioma (AG) and glioblastoma multiforme (GBM), after surgery and radiotherapy (and chemotherapy in some cases), with adequate organ function and KPS ≥60. TMZ is administered at 150–200 mg/m2/day on days 1–5 of each 28-day cycle, and PIFN is administered subcutaneously at 0.5 microgram/kg every week. Two 28-day cycles equals one course. Patients are re-evaluated with neurological examinations and neuro-imaging every 56 days. The study is powered to detect an improvement of the historic 6-month progression-free survival (PFS) from 15% to 30% for GBM patients and from 20% to 40% for AG patients.Results: Thirty-five patients have enrolled, 9 with recurrent AG and 26 with recurrent GBM, 15 women, 20 men, median age is 55 years (range 20–67), median KPS is 90 (range 70–100). Grade 3 or 4 toxicity occurred in 29 patients, 10 patients required dose reduction, 2 of TMZ, 8 of both drugs. Common grade 3 or 4 toxicities included leukopenia or thrombocytopenia in 15 patients. Best responses were no change in 23/34 (68%). Kaplan-Meier estimates revealed 38% of GBM patients and 44% of AG patients alive and free from progression at 6 months after enrollment. Conclusions: Preliminary results of TMZ combined with PIFN in recurrent AG and GBM, despite a lack of any objective radiologic responses, produced a 6 month PFS in both subgroups that surpasses the target 6 month PFS. This improved outcome appears to come at a price of increased toxicity. This combination may warrant further investigation in a randomized trial or with other anti-neoplastic agents. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering-Plough