Chimiothérapie des métastases d’origine colorectale jamais résécables: stratégie multiligne, thérapies ciblées

The advent of more active cytotoxic drugs (oxaliplatin, irinotecan), combined with targeted therapies and advances in surgery, has increased the survival of patients with metastatic colorectal cancer. The choice of first-line chemotherapy in case of patients with definitely non-resectable metastasis is guided by the merits and feasibility of aggressive treatment, history of prior adjuvant oxaliplatin, and tumor RAS status that has become essential. A major prognostic factor is patient’s access to all anticancer drugs, which is linearly correlated to survival. The same is probably true regarding targeted agents. The combination of doublet chemotherapy (fluoropyrimidine combined with oxaliplatin or irinotecan) and a targeted agent (bevacizumab or anti-EGFR antibodies if wild-type RAS) is the first-line standard of care for patients with non-resectable metastasis. In case of disease control after a 4–6 month induction bitherapy, treatment maintenance with a fluoropyrimidine (alone or combined with bevacizumab) until disease progression is a therapeutic option. Supplementary data are warranted to select subgroups of patients that may benefit from intermittent treatment to improve quality of life. In case of slowly growing metastatic disease and/or in frail patients, fluoropyrimidine (alone or combined with bevacizumab) may also be a first-line treatment option (oxaliplatin or irinotecan being added at the time of disease progression), without damage to survival compared with a strategy based on immediate doublet chemotherapy continued until progression or dose-limiting toxicity. On the other hand, survival rates ever achieved were obtained in selected patients after tricytotoxic-induction therapy (alone or combined with targeted agent) followed by maintenance treatment. These strategies deserve to be compared through further randomized trials.