Induction Treatment for Initially Unresectable Colorectal Liver Metastases: Combined Hepatic Arterial Infusion Pump Therapy With Systemic Therapy

Exclusion Criteria

• •ECOG performance status 0 or 1.
• •Life expectancy of at least 12 weeks.
• •Known mutation status of RAS and BRAFV600E.
• •Primary tumour in situ and resectable without neoadjuvant therapy.
• •Patient is eligible for surgery.
• •Patient is eligible for doublet chemotherapy.
• •Laboratory requirements: i.e. adequate bone marrow, liver and renal function (obtained within 15 days prior to registration).
• •* Hb ≥ 5.5 mmol/L
• •* absolute neutrophil count (ANC) ≥1.5 x 109/L
• •* platelets ≥100 x 109/L
• •* total bilirubin ≤ 1.5 times the upper limit of normal (ULN)
• •* ASAT/AST ≤ 5 x ULN
• •* ALAT/ALT ≤ 5 x ULN
• •* alkaline phosphatase ≤ 5 x ULN
• •* Serum creatinine ≤ 1.5 x upper limit of normal or a MDRD (eGFR) ≥ 45 ml/min;
• •* Prothrombin time or INR \< 1.5 x ULN, unless coumarin derivates are used. All patients using coumarin derivates will be treated with LMWH or DOAC instead.
• •Before registration, written informed consent must be given and signed according to ICH/GCP, and national/local regulations.
• •Prior hepatic radiation, resection, or ablation.
• •Any malignancy, comorbidity or condition that interferes with the planned study treatment or the prognosis of CRLM, determined by the treating physician.
• •History of prior malignancy except for the following: (a) malignancy treated with curative intent and with no evidence of active disease present within 3 years prior to inclusion, (b) curatively treated malignancies felt to be at low risk for recurrence by treating physician and MDT, (c) adequately controlled nonmelanomatous skin cancer, (d) adequately treated carcinoma in situ without current evidence of disease.
• •Obstructive primary tumour requiring emergency surgery, primary tumour necessitating a multivisceral resection/abdominoperineal resection or a rectal tumour requiring preoperative short-course radiotherapy or chemoradiotherapy for local tumour control.
• •MMR deficiency.
• •DPD-deficiency.
• •Pregnant or lactating women.
• •Serious concomitant systemic disorders that would compromise the safety of the patient or his/her ability to complete the study, at the discretion of the investigator.
• •Organ allografts requiring immunosuppressive therapy.
• •Serious non-healing wound, ulcer, or bone fracture.
• •Chronic treatment with corticosteroids (dose of ≥ 10 mg/day methylprednisolone equivalent excluding inhaled steroids).
• •Known serious infections (uncontrolled or requiring treatment).
• •History of psychiatric disability judged by the investigator to be clinically significant, precluding informed consent or interfering with compliance for HAIP-SYST or standard systemic therapy.
• •Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
• •Underlying liver disease including liver fibrosis and cirrhosis