Pharmacogenetics and Therapeutic Drug Monitoring for the Optimization of Fluoropyrimidine Treatment in Patients With Advanced Colorectal Cancer
Inclusion Criteria:
- Cytological or histological proven diagnosis of colorectal cancer, metastatic or
inoperable advanced disease, not amenable to curative therapy
- Measurable disease, defined as at least one lesion (outside of irradiated areas) that
can be measured in at least one dimension as ≥ 10 mm (≥ 15 mm in case of lymph nodes)
according to RECIST v1.1
- Tumor either wild-type KRAS or KRAS-mutated
- Indication for the therapeutic use of continuous intravenous 5FU over 48 hours
("deGramont" regimen) or oral Cp, either alone or in combination with other
anticancer drugs (including monoclonal antibodies or other molecularly-targeted
drugs)
- Eligible treatment regimens include: FOLFOX (FOLFOX 4, FOLFOX 6, modified FOLFOX 6,
FOLFOX 7), FOLFIRI, 5FU or Cp mono-chemotherapy ("deGramont" regimen), XELOX, XELIRI,
Capecitabine mono-chemotherapy
- All regimens may be combined with anti-VEGF or anti-EGFR targeted treatment such as
bevacizumab or cetuximab
- Patients receive first-line systemic treatment (previous adjuvant chemotherapy is
allowed, previous rectal radiochemotherapy is allowed if completed >/=1 months before
registration to the study)
- Written informed consent before registration to the trial
- The patient is willing to undergo pharmacogenetic and pharmacokinetic sampling and
analysis
- WHO performance status 0 or 1
- Female or male patients >18 years of age
- Adequate organ function (ANC, PLT, bilirubin 2xULN, creatinine clearance)
Exclusion Criteria:
- Known hypersensitivity to trial drug or any compounds of the drug
- Pregnant or breastfeeding women
- Patients with cerebral and/or leptomeningeal metastases are eligible, unless there is
a need for treatment with steroids
- Risk of rapid deterioration due to tumor symptoms or tumor complications
- Severe or uncontrolled cardiovascular disease (e.g. ACS, cardiac failure NYHA III or
IV, clinically relevant myopathy, history of myocardial infarction within the last 12
months, significant arrhythmias)
- Concurrent use of reversible or irreversible DPD-inhibitors, including brivudin,
sorivudin, eniluracil 5-chloro-2,4-dihydroxypyridine or with substances interfering
with the immunoassay, including theophylline and theobromine.
- Concurrent severe uncontrolled medical illness (judged by the investigator) which
could impair the ability of the patient to participate in the trial