[Targeted biotherapy: a revolution in the management of patients with colorectal cancer?].
In metastatic colorectal cancers (CRC), progress of chemotherapies in 40 years greatly increased their median survival from 6 to 8 months to 20 months. The first step of this development has been: the discovery of 5-fluorouracil, its optimisation by folinic acid and continuous perfusions. In the years 1990 to 2000, oxaliplatin and irinotecan opened the era of polychemotherapies. Their use in fisrt line treatment is not mandatory for all patients for whom chemotherapy may only have a palliative role without need for high response rates as for patients with symptomatic metastases or metastases hardly resectable. Targeted therapies have increased the life expectancy of the metastatic CRC and for some of them to facilitate secondary resections. Bevacizumab, an anti-VEGF antibody, in combination with an irinotecan based regimen increased dramatically the life expectancy with an acceptable toxicity, at least in patients of less than 70 years old. Efficacy of bevacizumab has also been demonstrated in combination with oxaliplatin based regimen (XELOX and FOLFOX) in first and second line, and in combination with 5-fluorouracil alone. Presently, bevacizumab is the most used targeted therapies in first line chemotherapy in combination with FOLFIRI, FOLFOX or XELOX. Cetuximab and panitumumab have first demonstrated their efficacy in the population of fully resistant patients to chemotherapies with a progression free survival gain of about 4 months as single treatment (cetuximab and panitumumab) or combined to irinotecan (cetuximab). Two studies have demonstrated that the adjonction of cetuximab in the first line treatment to FOLFIRI or FOLFOX increased the response rates. The presence of epithelial growth factor receptors (EGFR) at the cell'surface in immunohistochemistry is not a prerequisite for responses to cetuximab and panitumumab, and only patients with tumors without mutation of oncogene KRAS (60% of patients) are able to respond to anti-EGFR. This activity for the KRAS non mutated population has also been demonstrated in patients resistant to chemotherapy, compared to best supportive cases with panitumumab and with cetuximab. Thus, utilisation of anti-EGFR is only authorized in non mutated KRAS tumors and for the first time in metastatic CRC, we have the possibility to enrich the population in selecting non mutated KRAS population and to treat only patients having increased chance of response and of secondary resections of initially non resectable metastases. The cost of these targeted therapies is elevated and we need to find factors which will allow a personalized medicine with the dual selection of the good drug for the right patients.
Rougier
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P
Hôpital Ambroise-Paré, Assistance Publique-Hôpitaux de Paris, 92100 Boulogne, France. philippe.rougier@apr.aphp.fr
Mitry
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D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D001691:Biological Therapy; D017024:Chemotherapy, Adjuvant; D002985:Clinical Protocols; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D006801:Humans; D009362:Neoplasm Metastasis
D020533:Angiogenesis Inhibitors