Adverse events toxicity
Conditions
Interventions
irinotecan
toxicity
UGT1A1
Sponsors
Catharina-ziekenhuis
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Pathologically confirmed malignancy for which treatment with irinotecan is indicated at a dosing regimen of * 180 mg/m2 or 450-600mg flat dose in 2- or 3-weekly treatment schedules (see table 1) 2. Age * 18 years 3. Able and willing to give written informed consent 4. WHO performance status 0-2 5. Minimal acceptable safety laboratory values defined as a. ANC of * 1.5 x 109 /L b. Platelet count of * 100 x 109 /L c. Hepatic 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. d. Renal function (eGFR) * 50 ml/min OR creatinine * 1.5 x ULN
Exclusion criteria
Exclusion criteria: 1. Prior treatment with irinotecan 2. Patients with known substance abuse, psychotic disorders, and/or other diseases expected to interfere with study or the patient*s safety 3. Patients of Asian origin 4. Patients unable or unwilling to stop the use of (over the counter) medication or (herbal) supplements which can interact with irinotecan (e.g. by induction of inhibition of CYP3A4) (see Appendix 2 study protocol).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint of the study is the incidence of febrile neutropenia of UGT1A1 genotype-guided dosing during the first two cycle of irinotecan treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| * Incidence of grade *3 toxicity * Incidence of toxicity-related hospital admissions * Number of patients with treatment delay, defined as a delay of more than 2 days * Incidence of early treatment withdrawal * Pharmacokinetics of irinotecan and its metabolite SN-38 in UGT1A1*28 and/or *93 homozygous variant allele carriers. * Incidence of treatment delay due to prospective screening of UGT1A1 * Direct medical costs of irinotecan-based treatment * Progression free survival and overall survival * Bilirubin / conjugated bilirubin concentration ratio * The effect of additional polymorphisms other than UGT1A1*28 and *93 on treatment outcome in terms of toxicity and efficacy (survival and progression-free survival) | — |
Countries
The Netherlands
Outcome results
None listed