Phase II trial of erlotinib plus sirolimus for recurrent glioblastoma multiforme (GBM)

Abstract

2062 Background: Erlotinib, an EGF receptor kinase inhibitor, has limited single-agent activity in recurrent GBM patients. The antiglioma activity of EGFR inhibitors is enhanced by inhibitors of the mammalian target of rapamycin (mTOR), such as sirolimus, in preclinical studies. Methods: This phase II study assesses the antitumor activity of erlotinib plus sirolimus among recurrent GBM patients. Eligibility criteria: histologically confirmed GBM; age ≥18 years; KPS ≥ 70%; adequate hepatic, renal, and bone marrow function and lack of prior EGFR or mTOR-directed therapy. Patients not on enzyme-inducing anticonvulsants (EIAC; phenytoin, carbamazepine, oxcarbazepine and phenobarbitol) receive 150 mg of erlotinib and 5 mg of sirolimus per day, while those on EIAC receive 500 mg of erlotinib and 10 mg of sirolimus per day. Patients are evaluated after every other 28-day cycle. The primary endpoint is 6-month progression-free survival. Results: To date 27 patients have enrolled with a median age of 53.2 years (r...