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Hépato-Gastro & Oncologie Digestive

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Metastasic colorectal cancer: Which treatment in the first-line setting? Volume 17, special issue 5, Cancer colorectal : acquis thérapeutiques récents

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Oncologie, Oncogénétique et Endoscopie Digestives, Département de Médecine, Institut Gustave Roussy, Université Paris Sud, Villejuif

The advent of more active drugs (oxaliplatin, irinotecan, bevacizumab, anti-EGFR agents) and advances in surgery have increased the survival of patients with metastatic colorectal cancer. The choice of first-line treatment is guided by the merits and feasibility of aggressive treatment (patient refusal, frail patient, aggressive disease, and potentially resectable metastases), history of prior adjuvant oxaliplatin, and tumor KRAS status. A major prognostic factor is patient access to all anticancer drugs, which is linearly correlated to survival. The combination of doublet chemotherapy (fluoropyrimidine plus oxaliplatin or irinotecan) and a targeted agent (bevacizumab or anti-EGFR agents) is the first-line standard of care for patients with non-resectable metastases. There is no benefit to administer anti-EGFR agents in case of tumor KRAS mutations. In cases of tumor wild-type KRAS status, either bevacizumab or anti-EGFR agents can be administered. Efficacy data suggest that bevacizumab is the targeted agent of choice for first-line treatment in most patients, while anti-EGFR agents could be reserved for subsequent lines without damage to survival. In case of slowly growing metastatic disease and/or in frail patients, fluoropyrimidine (alone or plus bevacizumab) may also be a maintenance treatment after doublet chemotherapy, or even a first-line treatment (oxaliplatin or irinotecan being added at the time of disease progression), without damage to survival compared to a strategy based on immediate doublet chemotherapy continued until progression or dose-limiting toxicity. In case of potentially resectable metastases, regimens providing a maximal objective response rate (triplet therapies, hepatic arterial chemotherapy) should be preferred. In case of initially resectable metastases, the standard is perioperative chemotherapy using FOLFOX 4 regimen.