A phase II study of radiation with concomitant and then sequential temozolomide (TMZ) in patients (pts) with newly diagnosed supratentorial high grade malignant glioma (MG) who have undergone surgery with carmustine (BCNU) wafer insertion

Abstract

1547 Background: Prior studies demonstrated the effectiveness of both BCNU wafer (Gliadel) and TMZ (Temodar) as adjunctive therapies to resection and radiation therapy (RT) in pts with initial high grade MG. (Westphal et al. Neuro-Onco 2003; Stupp et al. JCO 2002) This study assessed the safety and efficacy of BCNU wafer and TMZ in combination. Methods: This is a phase II, multicenter, trial. Eligible pts were 18–72 years (yrs) of age with surgically operable, initial high grade MG. Enrollment began in July 2003 and continues. After resection and BCNU wafer insertion, pts received concomitant treatment with daily RT 2 Gy (≤total 60 Gy) + TMZ 75 mg/m2 (≤45 days) followed by monthly TMZ (200 mg/m2 daily x 5 every 28 days, ≤18 cycles). Endpoints include survival and progression-free survival (PFS), which were estimated with the Kaplan-Meier Method: Results: As of November 2004, 16 pts have been enrolled at 2 centers. Glioblastoma multiforme was diagnosed in 15 pts. Median (range) age is 59 (29–71) yrs and median Karnofsky Performance Status is 95 (70–100). After a median follow-up of 7 (1–17) months, 7 pts have had a recurrence and 3 pts have died; 8 pts remain on active treatment and one patient withdrew consent. Median survival and PFS have not been reached. The 1-yr survival rate is 63%, and the 1-year PFS rate is 51%. Adverse events include deep vein thrombosis (3 pts), pulmonary embolism (4 pts), sterile brain abscess (1 pt) and bacterial pneumonia (1 pt). Conclusions: These data suggest combination therapy with BCNU wafers followed by RT/ TMZ may be an effective regimen in pts with initial high-grade resectable MG. Randomized trials will be needed to ultimately assess efficacy. The incidence of DVT and PE within 60 days of surgery in this pt population, despite the standard use of postoperative compression stockings and sequential compression devices, merits further evaluation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Guilford Guilford, Schering-Plough Guilford