Phase I trial of erlotinib with radiation therapy in patients with glioblastoma multiforme: results of North Central Cancer Treatment Group protocol N0177.

PURPOSE

To evaluate the toxicity and maximum tolerated dose (MTD) of erlotinib plus radiation therapy (RT) in patients with glioblastoma multiforme (GBM) in a multicenter phase I trial.

METHODS AND MATERIALS

Patients were stratified on the basis of the use of enzyme-inducing anticonvulsants (EIACs). After resection or biopsy, patients were treated with erlotinib for 1 week before concurrent erlotinib and 6 weeks (60 Gy) of RT and maintained on erlotinib until progression. The erlotinib dose was escalated in cohorts of 3 starting at 100 mg/day.

RESULTS

Twenty patients were enrolled and 19 were evaluable for the MTD and efficacy endpoints. Of these patients, 14 were males and 5 were females, with a median age of 54 years. Seven had undergone biopsy only, 5 had subtotal resections, and 7 had gross total resections. The highest dose level was 150 mg/day erlotinib for patients not on EIACs (Group 1) and 200 mg/day for patients on EIACs (Group 2). MTD was not reached in either group. In Group 1 at 100 mg (n=6) and at 150 mg (n=4), only 1 dose-limiting toxicity (DLT) occurred (stomatitis at 100 mg). No DLTs have occurred in Group 2 at 100 mg (n=3), 150 mg (n=3), and 200 mg (n=3). With a median follow-up of 52 weeks, progression was documented in 16 patients and 13 deaths occurred. Median time to progression was 26 weeks, and median survival was 55 weeks.

CONCLUSION

Toxicity is acceptable at the current doses of erlotinib plus RT. The study was modified to include concurrent and adjuvant temozolomide, and accrual is in progress.