Background: Based on our pre-clinical data, we hypothesized that sequencing chemotherapy with erlotinib would increase the tumor response rate in patients with metastatic colorectal cancer.
Patients and methods: A phase II trial (planned n=58) using second-line therapy for metastatic colorectal cancer with either oxaliplatin-based (mFOLFOX6) or irinotecan-based (FOLFIRI) combination chemotherapy and 100 mg erlotinib daily on days 3-8 after each infusion (days 1 and 2) every 14 days. The primary endpoint was the response rate compared to the historical response rate.
Results: The FOLFIRI/erlotinib arm met the pre-specified response rate criteria of at least 10% to expand accrual to the intended sample size. The trial was halted after an interim safety analysis (n=11) due to excess grade 3 neutropenia, dose reductions and treatment delays. Grade 3 or 4 neutropenia was observed in 64% of patients. The response rate was 18%.
Conclusion: In second-line treatment for metastatic colorectal cancer, mFOLFOX6 or FOLFIRI with erlotinib in a sequence-dependent fashion is not feasible despite potential promising activity.
Keywords: 5-FU; 5-fluorouracil; EGFR; Erlotinib; colorectal cancer; epidermal growth factor receptor; irinotecan; oxaliplatin.
Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.