N IV infusion 5FU continuous infusion 2400 mg/m2, 46 h IV infusionoxaliplatin-based
N IV infusion 5FU continuous infusion 2400 mg/m2, 46 h IV infusionoxaliplatin-based chemotherapy (i.e., no prior progression through FOLFOX or XELOX and LAIR1 Protein Accession residual neuropathy grade 2), the finish of treatment technique is HGF Protein Source defined at the date of progression right after this reintroduction.Common considerations for dose modificationsB. Doses in modified FOLFOX6-bevacizumab H0 H+1 Bevacizumab five mg/kg, 300 min IV infusion Oxaliplatin 85 mg/m2 in 250 ml glucose 5 , two h infusion Folinic acid 400 mg/m2 (racemic, or L-form 200 mg/m2) in 250 ml glucose five option, 2 h IV infusion H+3 H + 3.5 5FU bolus 400 mg/m2 in one hundred ml glucose five option, 15 min IV infusion 5FU continuous infusion 2400 mg/m2, 46 h IV infusionC. Doses in modified XELOX-bevacizumab H0 H+1 Bevacizumab 5 mg/kg, 300 min IV infusion Oxaliplatin 85 mg/m2 in 250 ml glucose 5 , two h infusionDay 1-8 Capecitabine 1250500 mg/m2 bid, from day 1 (inside the evening) to day 8 (inside the morning)Cycles every two weeks, till disease progression, unacceptable toxicity or withdrawal of consentToxicities must be graded in accordance with the NCI CTCAE v4.0 [37]. For toxicities regarded by the investigator unlikely to create into severe or life-threatening events (e.g., alopecia, altered taste), treatment ought to be continued in the same dose without reduction or interruption. Furthermore, no dose reductions or interruptions are necessary for anemia (non-hemolytic) as this could be satisfactorily managed by transfusions and/or erythropoiesisstimulating agent. If numerous toxicities with distinctive grades or severities occur at the very same time, dose modifications needs to be completed as outlined by the greatest reduction applicable. If toxicity is deemed to be due solely to among the list of drugs (e.g., hand-foot syndrome secondary to fluoropyrimidines, neurotoxicity as a consequence of oxaliplatin, hypertension and proteinuria as a result of bevacizumab, acne-like syndrome on account of cetuximab or panitumumab), other drugs don’t require a dose adjustment. Dosage adjustment for isolated abnormal lab values must be based on parameters at start of a therapy cycle (or one operating day prior to). According to by far the most serious toxicity knowledgeable since the final remedy, the scheduled treatment rest period must be extended until all toxicities subside to grade 1 or significantly less.Salvage surgeryfollowed by reintroduction of oxaliplatin. In case of early progression (i.e., occurring significantly less than 3 months right after the final administration of oxaliplatin) and/or residual neuropathy contra-indicating oxaliplatin reintroduction, maintenance therapy need to be followed by second-line therapy.Second-lineSecond-line treatment consists of irinotecan-based chemotherapy (mFOLFIRI3 or FOLFIRI1) with bevacizumab till disease progression or unacceptable toxicity. Frail sufferers (ECOG PS 2 and/or total serum bilirubin 3xUNL) are permitted to receive an anti-EGFR agent alone (cetuximab or panitumumab).Third-lineSecondary surgery of metastases is authorized providing that the following conditions are respected: prior assessment of tumor response (i.e., at least a single tumor evaluation just after randomization) and intent to attain a comprehensive surgical resection (R0). In case of R0 or R1 resection, the usage of a postoperative therapy and selection on the therapeutic regimen are left to the investigator’s discretion. However, FOLFOX is advised in each arms. In case of R2 resection, the patient resumes the therapeutic tactic as outlined by allocated remedy arm.Study endpointsAt the end of second-line t.