Extended duration temozolomide in patients with glioblastoma multiforme.

Abstract

e12538 Background: Standard treatment for glioblastoma multiforme (GBM) includes surgical resection, temozolomide (TMZ) with radiotherapy, and adjuvant TMZ. Phase III data has shown that patients treated with 6 months of adjuvant TMZ had a median overall survival (OS) of 14.6 months with a 26.9% PFS and 61.1% OS at 1 year. The optimal duration of adjuvant therapy and whether additional agents may improve outcome is a matter of intense study. Methods: From 2002 to 2009, consecutive patients from a regional cancer center were assessed. To be eligible, patients required histological confirmation of GBM, a good performance status, and must have received concurrent radiation and TMZ. Each patient went on to receive up to 30 cycles of TMZ (150-200 mg/m2) concurrent with cis-retinoic acid (CRA) (50 mg/m2 BID). Treatment was stopped or changed if there was intolerance to therapy or clinical/radiologic evidence of progression. TMZ was continued if patients were intolerant only to the side effects of CRA. Results: Of the 79 patients that were included, mean age was 57 and 63.3% were male. The mean number of cycles of TMZ given was 8.5, with 2 patients receiving 30 cycles and 7 receiving 24 cycles. 18 patients (22.7%) received at least 12 cycles of TMZ. The mean number of TMZ cycles given concurrently with CRA was 6.7, with 15 patients (19%) receiving at least 12 concurrent cycles. No patients discontinued TMZ due to intolerance. Median OS was 17.1 months, and median progression-free survival (PFS) on TMZ was 9.6 months. The 12 month PFS was 36.7% and OS was 70.9%. Multivariable analysis determined that the extent of surgery (biopsy: HR 4.1, p = 0.003; partial resection: HR 2.3, p = 0.027) and age (HR 1.03, p = 0.006) were independently associated with survival. Survival did not improve over time. Conclusions: Extended duration TMZ is a well- tolerated treatment for up to 30 cycles. Patients treated in this manner had favorable survival compared to standard therapy. The combination of TMZ and CRA given monthly until progression or intolerance should be studied in a prospective randomized trial in the adjuvant setting. No significant financial relationships to disclose.