Treatment Strategies in Colorectal Cancer Patients With Initially Unresectable Liver-only Metastases

Prior treatment

• Major cardiovascular events (myocardial infarction, severe/unstable angina, congestive heart failure, CVA) within 12 months before randomisation
• Previous systemic treatment for metastatic disease; previous adjuvant treatment is allowed if completed ≥ 6 months prior to randomisation
• Previous surgery for metastatic disease
• Previous intolerance of study drugs in the adjuvant setting
• Any concomitant experimental treatment.

Other illness

• Serious comorbidity or any other condition preventing the safe administration of study treatment (including both systemic treatment and surgery)
• Uncontrolled hypertension, or unsatisfactory blood pressure control with ≥3 antihypertensive drugs
• Second primary malignancy within the past 5 years with the exception of adequately treated in situ carcinoma of any organ or basal cell carcinoma of the skin, or second primary colorectal cancer.

Other

• Extrahepatic metastases, with the exception of small (≤ 1 cm) extrahepatic lesions that are not clearly suspicious of metastases
• Unresectable primary tumor
• Pregnant or lactating women

• Histological proof of colorectal cancer
• Initially unresectable metastases confined to the liver according to CT scan, obtained ≤3 weeks prior to registration. Unresectability should be confirmed by the liver expertpanel. Patients with small (≤ 1 cm) extrahepatic lesions that are not clearly suspicious of metastases are eligible
• Known mutation status of RAS and BRAF
• WHO performance status 0-1 (Karnofsky performance status ≥ 70)
• Age ≥ 18 years
• No contraindications for liver surgery
• In case of primary tumor in situ: tumor should be resectable
• In case of resected primary tumor: adequate recovery from surgery
• Adequate organ functions, as determined by normal 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 ≤ 5x ULN)
• Life expectancy \> 12 weeks
• Expected adequacy of follow-up
• Written informed consent