Impact of Biweekly and Triweekly Dosing Regimens

Prior treatment

• previous systemic treatment for metastatic disease (adjuvant treatment if completed more than 6 months ago is allowed)
• MSI-H tumors if there’s no contraindication to immunotherapy
• patients who are expected to become eligible for targeted biological therapy after a certain period of time, and who receive FOLFIRI alone only at the beginning of the therapeutic sequence (e.g., in the postoperative period), are not eligible to participate in the study (targeted biological therapy administered in a later line of treatment is permitted within the study)
• patients eligible for conversion therapy (systemic treatment preceeding surgical resection of CRC metastases)
• patients requiring rapid regression (preferentially treated with FOLFOX)
• severe organ dysfunction; severe internal or chronic infectious disease excluding oncology treatment; acute, severely symptomatic infectious disease within 2 weeks prior to treatment
• other treatment for oncological purposes within 4 weeks prior to treatment (palliative, decompressive or analgetic radiotherapy is allowed)

Other illness

• history of hypersensitivity to study agents
• oligometastatic disease where the tumor board indicates ablative local treatment of metastases

Other

• known complete DPD deficiency or UGT1A1 polymorphysm (screening is not part of the study due to access difficulties in routine clinical practice)

• patients aged 18 years or older (no upper age limit)
• patients ineligible for targeted biological therapy (see table 8 in the detailed protocol) or patients who refuse targeted biological therapy
• histologically proven metastatic colorectal adenocarcinoma from the primary tumour
• consent to participate in the study
• ECOG performance score of 0-2
• normal haematological and organ functions (serum AST, GOT, GPT -and creatinine- below three times the upper limit of normal, serum bilirubin is below 5xULN, absolute neutrophil count is > 1,5G/L, platelet count >100 G/L; higher AST/GOT/GPT values are allowed in case of liver metastasis upon the investigator’s decision)
• disease measurable according to RECIST 1.1 and eligibility for delivering CT scan with contrast agents
• use of high efficacy contraception
• life expectancy of at least 3 months as judged by the treating physician
• molecular pathology testing of the tumor specimen (RAS/RAF status + MSI status)