S-1 versus capecitabine in the first line treatment of metastatic colorectal cancer patients, the SALTO randomised phase III study of the Dutch Colorectal Cancer Group. A safety evaluation of oral fluoropyrimidines.

INTERVENTION: Trade Name: Teysuno Pharmaceutical Form: Capsule Trade Name: Xeloda Pharmaceutical Form: Film‐coated tablet Trade Name: Xeloda Pharmaceutical Form: Film‐coated tablet Trade Name: Teysuno Pharmaceutical Form: Capsule Trade Name: Teysuno Pharmaceutical Form: Capsule Trade Name: Teysuno Pharmaceutical Form: Capsule Trade Name: Teysuno Pharmaceutical Form: Capsule CONDITION: Metastatic Colorectal Cancer ; MedDRA version: 17.1 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 100000004864 Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: Main Objective: To determine the incidence of HFS in first line treatment with S‐1 compared to capecitabine in patients with metastatic colorectal cancer. Primary end point(s): A decreased incidence of HFS from 30 % for capecitabine to 10 % for S‐1. Secondary Objective: • Incidence of grade 3 hand‐foot syndrome; • Incidence of other toxicities; • Progression‐free survival; • Response rate ; • Overall survival; Timepoint(s) of evaluation of this end point: 6 months after the last patient has been included. SECONDARY OUTCOME: Secondary end point(s): Overall survival calculated from date of randomisation to death or to last known to be alive. ; Response rate after the 6th cycle of treatment. ; Adverse events according th NCI CTC criteria ; Progression free survival calculated from randomisation to date of first progression or death whichever comes first Timepoint(s) of evaluation of this end point: 6 months after the last patient has been included. INCLUSION CRITERIA: • Histological proof of colorectal cancer. • Distant metastases (patients with only local recurrence are not eligible) • Unidimensionally measurable disease (=1 cm on spiral CT scan or =2 cm on chest X‐ray; liver ultrasound is not allowed). Serum CEA may not be used as a parameter for disease evaluation. • In case of previous radiotherapy, at least one measurable lesion should be located outside the irradiated field. • Age = 18 years • Planned first line treatment with capecitabine monotherapy with or without bevacizumab. • WHO performance status 0‐2 (Karnofsky PS =70%); • Laboratory values obtained within 2 weeks prior to randomisation: • adequate bone marrow function (Hb = 6.0 mmol/L, absolute neutrophil count =1.5 x 109/L, platelets = 100 x 109/L), renal function (serum creatinine = 1.5x ULN and creatinine clearance, Cockroft formula, =30 ml/min), liver function (serum bilirubin = 2 x ULN, serum transaminases = 3 x ULN withou