Hôpital Saint-Antoineservice d’oncologie médicale 184, rue du Faubourg-Saint-Antoine 75571 Paris cedex 12, France
Several therapeutic strategies exist beyond the first line of chemotherapy. They depend on the type of treatment received in first-line, its efficacy, toxicity and/or contraindications (oxaliplatin and neuropathy, irinotecan and jaundice, bevacizumab and arterial thromboembolic events), the patient’s health status and wishes, and the tumor characteristics (e.g., KRAS status). Treatment must be decided within a multidisciplinary staff and discussed with the patient. Data from randomized trials suggest that chemotherapydrugs used in second-line treatment provide a survival benefit compared with supportive care alone. Following fluorouracil failure, several chemotherapy regimens are active: FOLFIRI, FOLFOX, and IROX. After failure of irinotecan-based first-line treatment, FOLFOX appears the best choice. The combination of bevacizumab with FOLFOX prolongs survival. For patients treated with FOLFOX in first-line followed by maintenance 5-FU monotherapy, reintroduction of oxaliplatin can be proposed after disease progression, depending on the length of oxaliplatin-free interval. After FOLFOX failure, irinotecan-based chemotherapy appears to be the most appropriate option. Cetuximab and panitumumab increase the effectiveness of irinotecan in patients with wild-type KRAS tumor, and are also active as monotherapy in third- or fourth-line therapy. In case of objective response to chemotherapy, it is important to discuss the possibilities of surgical treatment of metastases if rendered resectable. Finally, several studies are currently underway to determine the role of different targeted therapies and the type of combined chemotherapy in the treatment strategy of metastatic colorectal cancer beyond the first-line.