A phase 2 study of temozolomide in patients affected by pretreated metastatic colorectal cancer with MGMT promoter methylation.

629Background: Presently few options are available for pts with mCRC who failed standard treatments and prognosis remains grim. MGMT promoter methylation is a frequent and early event in CRC tumorigenesis. This epigenetic silencing is a predictor of response to the alkylating drug TMZ in glioblastoma. Preclinical evidences and a couple of clinical cases showed TMZ activity in pts affected by mCRC with MGMT silencing. We designed a study to evaluate the efficacy and safety of TMZ in pts with refractory mCRC harboring MGMT promoter methylation. While the trial was ongoing three analogous studies, reporting discordant results, were published. Methods: This was a 3-institutional, single arm, phase 2 trial, planned according to a 2-stage Simon’s optimal design. The primary endpoint was ORR. Secondary outcomes included DCR, OS, PFS and safety. A first cohort of 21 pts was accrued: if more than 1 response was observed a second cohort of 20 pts would be enrolled; if 4 or fewer responses were observed by the end o...