Prognostic Factors for Metastatic Colorectal Cancer Patients Undergoing Irinotecan-Based Second-Line Chemotherapy

摘要

Background: No reports about factors that predict prognosis after second-line chemotherapy for metastatic colorectal cancer have been published. Methods: We retrospectively analyzed 124 patients with metastatic colorectal cancer who received irinotecan-based second-line chemotherapy after first-line folinic acid/5-fluorouracil (5-FU)/oxaliplatin (FOLFOX) with or without bevacizumab. Results: A multivariate Cox model revealed 5 prognostic factors for worse survival: ECOG performance status 2, pathologically poorly differentiated adenocarcinoma, peritoneal metastasis, progression-free survival of first-line FOLFOX 1 , 2 After failure of FOLFOX, FOLFIRI [folinic acid/ (5-FU)/irinotecan] or irinotecan monotherapy is usually administered in the second-line setting. 3 , 4 The results of a large observational study have also suggested that continued use of bevacizumab during second-line therapy may provide additional benefit. 1 Cetuximab, a recombinant, human-mouse chimeric monoclonal IgG1 antibody that specifically targets epidermal growth factor receptor (EGFR) has been shown to improve the prognosis of MCRC significantly compared to best supportive care alone in the third-line setting. 5 Furthermore, combining cetuximab with irinotecan results in a higher response rate than cetuximab alone, even in patients with irinotecan-refractory disease, suggesting that cetuximab may restore chemosensitivity in these patients. 6 The EPIC trial was a large phase III study that compared irinotecan plus cetuximab to irinotecan monotherapy as second-line treatment in patients with MCRC following failure of oxaliplatin-based therapy. 7 Although the primary end point of improved survival was not achieved (10.7 vs 10.0 months, p = .71), patients in the combination arm experienced a superior response rate and progression-free survival (PFS). Approximately half of the patients in the irinotecan monotherapy arm received cetuximab after irinotecan failure, which may have contributed to the similar overall survival rates in the 2 arms. However, 35% of patients in the irinotecan group were unable to receive any third-line chemotherapy, most likely due to rapid tumor progression. 7 Thus, it was suggested that cetuximab with irinotecan may be better than irinotecan as second-line therapy for patients with rapidly progressing disease. So far, no reports about factors that predict the prognosis after second-line irinotecan or probability of receiving third-line therapy have been published. To address this issue, we conducted the following retrospective analysis of MCRC patients who received irinotecan-based chemotherapy as second-line treatment after first-line FOLFOX.