The goal of this phase III, open-label, non-inferiority randomized controlled clinical trial is compare upfront dose-reduced chemotherapy with the standard dose chemotherapy in older patients ( ≥70 years) with metastasized colorectal cancer, with regard to progression-free survival (PFS). The choice between monotherapy (a fluoropyrimidine) and doublet chemotherapy (a fluoropyrimidine with oxaliplatin) will be made for each individual patient based on expected risk of chemotherapy toxicity (according to the G8 screening). Patients classified as low risk of toxicity will be randomized between doublet chemotherapy in either full-dose, or with an upfront dose-reduction of 25%. Patients classified as high risk will be randomized between monotherapy in either full-dose or upfront dose-reduction. Primary outcome is PFS. Secondary endpoints include grade ≥3 toxicity, QoL, physical functioning, overall survival, number of treatment cycles, dose reductions, hospital admissions, cumulative received dosage and cost-effectiveness.
Inclusion Criteria: * Patients aged 70 years or older with colorectal cancer and distant metastases without localized treatment options. * Patients who are candidates for first-line palliative chemotherapy as judged by their treating oncologist * Being able to understand the Dutch language * Adequate bone marrow and organ function: Absolute neutrophil count (ANC) \> 1.5 x 10\^9 mmol/L, Hemoglobin (Hb) \> 6.0 mmol/L, Platelets \>100 x 109 / L, Serum bilirubin ≤ 2 x upper limit of normal (ULN), serum transaminases ≤ 3 x ULN without presence of liver metastases or ≤ 5x ULN with presence of liver metastases. Exclusion Criteria: * Patients who received prior palliative chemotherapy * Patients in whom local treatment of metastases is scheduled (i.e. liver surgery or stereotactic radiotherapy) * Candidates for triple chemotherapy * Patients who received prior adjuvant chemotherapy in the one year before inclusion in the study (chemotherapy before that time is allowed) * Patients with complete or incomplete dihydropyrimidine dehydrogenase (DPD) deficiency * Patients with Microsatellite instable (MSI)-high colorectal cancer * Patients with HIV or active hepatitis * Patients with severe kidney failure (defined as GFR ≤30ml/min) * Patients with severe cognitive deficits making informed consent not possible