Phase II study of dacarbazine for metastatic colorectal cancer: Final results with MGMT analysis.

摘要: 3581 Background: O6-methylguanine-DNA-methyltransferase (MGMT) is a DNA repair protein removing mutagenic and cytotoxic adducts from O6-guanine in DNA. Approximately 40% of colorectal cancers (CRCs) display MGMT deficiency due to promoter hypermethylation leading silencing the gene. Alkylating agents, such as dacarbazine, exert their antitumor activity by methylation at O6–guanine site, inducing base pair mismatch, therefore dacarbazine could be enhanced CRCs lacking MGMT. We conducted phase II study with who had failed standard therapies (oxaliplatin, irinotecan, fluoropyrimidines, cetuximab or panitumumab if KRAS wild type). Methods: All patients tumor tissue assessed for double-blind treatment outcome. Patients received 250 mg/m2 i.v. qd 4 consecutive days q21 until PD intolerable toxicity. employed Simon two-stage design determinate ORR would ≥ 10%. Secondary endpoin...