Inclusion Criteria:

• Histology and staging disease

  • Histologically proven CRC; advanced disease, not amenable to curative surgery;
  • Of Note: In case of a single metastasis, histological or cytological proof of colorectal carcinoma should be obtained prior to randomisation.
  • Measurable or evaluable disease; Serum CEA as the only parameter for disease activity is not allowed.

• General conditions

  • Written informed consent;
  • Age 18 years and above;
  • WHO performance status 0-2;
  • Adequate bone marrow function(WBC > 3.0 x 109/L, platelets > 100 x 109/L, Hb > 6 mmol/L);
  • Adequate hepatic function: total bilirubin < 1. 5 x upper normal limit, ASAT and ALAT < 3 x upper normal limits; in case of liver metastases < 5 x upper normal limits
  • Adequate renal function: creatinin < 1. 5 x upper normal limits.

• Other

  • Expected adequacy of follow-up.

Exclusion Criteria:

• General conditions

  • Pregnancy or lactation;
  • Patients (M/F) with reproductive potential not implementing adequate contraceptives measures.

• Prior or current history

  • Prior chemotherapy for advanced disease; prior adjuvant chemotherapy is allowed provided that the last administration was given > 6 months prior to randomisation.
  • Serious concomitant diseases preventing the safe administration of chemotherapy or likely to interfere with the study assessments;
  • Serious active infections;
  • Inflammatory bowel disease or other diseases associated with chronic diarrhoea;
  • Previous extensive irradiation of the pelvis or abdomen;
  • Other malignancies in the past 5 years with the exception of adequately treated carcinoma in situ of the cervix or squamous or basal cell carcinoma of the skin.

• 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.