The Role of the Tumor Molecular Profile (CMS), UGT1A1 Genotype and Beta-glucuronidase Activity of the Intestinal Microbiota for Treatment Efficiency, Toxicity, Survival and Quality of Life in Patients With Metastatic or Unresectable Colorectal Cancer During Irinotecan-based Systemic Treatment

Irinotecan-based systemic therapy is a treatment option for metastatic or unresectable colorectal cancer. However, this therapy has two major disadvantages, namely, an unpredictable response to the treatment and severe side effects, for instance diarrhea or a low white blood cell count (neutropenia). Therefore, the OPTIMA study was developed to find out if biomarkers, such as the molecular profile of the tumor, the UGT1A1 genotype and activity of the bacterial enzyme β-glucuronidase, can predict response and side effects during irinotecan treatment. By looking at these biomarkers, treatments could be more personalized, resulting into enhanced therapy efficiency, increased optimal survival and a better quality of life.

Inclusion Criteria:Adult patient: 18 years of age or olderPatients diagnosed with metastatic or irresectable CRC, who will be treated with irinotecan-based combination therapy (FOLFIRI/FOLFOXIRI) +/- bevacizumab as first line treatment.WHO performance status 0-2Minimal acceptable safety laboratory values defined as:ANC of ≥ 1.5 x 109 /LPlatelet count of ≥ 100 x 109 /LHepatic function as defined by serum bilirubin ≤ 1.5 x ULN, ALAT and ASAT ≤ 2.5 x ULN; in case of liver metastases ALAT and ASAT ≤ 5 x ULN.Renal function (eGFR) ≥ 50 ml/min or OR creatinine ≤ 1.5 x ULNWritten informed consentExclusion Criteria:Microsatellite instability (MSI) or deficient MMR proteinsPregnant or nursingPresence of ileostomyAsian ethnicityOther systemic treatment is less than one month before the start of the irinotecan-based treatmentTherapeutic antibiotic use is less than three months before the start of the irinotecan-based treatmentAbdominal radiotherapy is less than two weeks before the start of the irinotecan-based treatmentPrior treatment with irinotecanPhysically or mentally incapable or incompetentMore than 25% irinotecan dose reduction at the start of treatment (dose reductions during treatment are allowed), with exception of dose reduction due to UGT1A1 mutation.