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.

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 160

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 without presence of liver metastases or * 5x ULN with presence of liver metastases).;* Life expectancy > 12 weeks.;* Negative pregnancy test in women with childbearing potential.;* Expected adequacy of follow-up.;* Institutional Review Board approval.;* Written informed consent.

Exclusion Criteria

* Prior adjuvant treatment for stage II/III colorectal cancer completed within 6 months prior to randomisation.;* Any prior adjuvant treatment after resection of distant metastases.;* Any prior systemic treatment for advanced disease.;* History or clinical signs/symptoms of CNS metastases.;* History of a second malignancy <5 years with the exception of adequately treated carcinoma of cervix or basal/squamous cell carcinoma of skin.;* Previous intolerance of capecitabine.;* Known dihydropyrimidine dehydrogenase (DPD) deficiency or treatment within 4 weeks with DPD inhibitors, including sorivudine or its chemically related analogues such as brivudine.;* Planned radical resection of metastases after downsizing by systemic treatment.;* Significant cardiovascular disease < 1 yr before randomisation (symptomatic congestive heart failure, myocardial ischemia or infarction, unstable angina pectoris, serious uncontrolled cardiac arrhythmia, arterial thrombosis, cerebrovascular event, pulmonary embolism).;* Any significant cardiovascular events during previous fluoropyrimidine therapy.;* Chronic active infection.;* Any other concurrent severe or uncontrolled disease preventing the safe administration of study drugs.;* Any impairment of gastrointestinal function or *disease that may significantly impair the absorption of oral drugs (i.e. uncontrolled nausea, vomiting, diarrhoea (defined as ³CTC grade 2), malabsorption syndrome, bowel obstruction, or inability to swallow tablets).;* Concomitant treatments: concomitant (or within 4 weeks before randomisation) administration of any other experimental drug under investigation; concurrent treatment with any other anti-cancer therapy. ;* Continuous use of immunosuppressive agents (except the use of corticosteroids as anti-emetic prophylaxis/treatment).;In case of treatment with bevacizumab:;* Uncontrolled hypertension, i.e. consistently > 150/100 mmHg.;* Use of * 3 antihypertensive drugs.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>To assess the incidence of HFS in first line treatment with S-1 compared to<br /><br>capecitabine in patients with metastatic colorectal cancer.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>To evaluate and assess:<br /><br>* Incidence of grade 3 hand-foot syndrome<br /><br>* Incidence of other toxicities<br /><br>* Progression-free survival<br /><br>* Response rate<br /><br>* Overall survival</p><br>