Clinical trial NCT00838370: Pharmacogenomic and Pharmacokinetic Safety and Cost-saving Analysis in Patients Treated With Fluoropyrimidines
Official title: Pharmacogenomic and Pharmacokinetic Safety and Cost-saving Analysis in Patients Treated With Fluoropyrimidines
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Keywords: Pharmacogenetics
cost-benefit analysis
toxicity
antineoplastic drugs
Dihydropyrimidine Dehydrogenase
Lead sponsor: The Netherlands Cancer Institute
Sponsor class: OTHER
First posted: 2009-02-06
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The primary purpose of this study is to prospectively determine whether capecitabine and 5-FU-induced toxicity is preventable by dose reduction prior to start of the first administration in patients heterozygous or homozygous mutant for DPYD\*2A, and to determine whether this strategy is cost-effective. Secondly, an individualized treatment algorithm for capecitabine and 5-FU therapy in DPYD\*2A mutant patients will be developed and the pharmacokinetic profile of capecitabine and 5-FU will be assessed.

Detailed description: Patients exhibiting a genetically determined disorder (DPYD\*2A) in the metabolic degradation of the frequently used anticancer agents capecitabine and 5-FU (fluoropyrimidines) are at high risk of development of severe and life-threatening toxicity during standard treatment with these compounds. Treatment and recovery of this fluoropyrimidine-induced severe toxicity often requires prolonged periods of hospitalization.

Screening for DPYD\*2A in patients to treat with fluoropyrimidine drugs with subsequent dose adjustments in mutant individuals prior to start of therapy will possibly reduce the number of severe toxicity events. Furthermore, by reducing the frequency and/or duration of hospitalization, substantial medical costs can be saved, making this a cost-effective strategy.

Eligibility criteria: Inclusion Criteria:

* Histological proof of cancer
* patient is considered for treatment with capecitabine or 5-FU
* hetero- or homozygous mutant for DPYD\*2A
* able and willing to give written informed consent
* able and willing to undergo blood sampling for pharmacokinetic analysis
* life expectancy 3 months or longer
* acceptable safety laboratory values (ANC, platelet count, ASAT, ALAT, creatinine,
* WHO performance status 0-2
* no radio- or chemotherapy within the last 3 weeks prior to study entry

Exclusion Criteria:

* patients with known alcoholism, drug addiction and/or psychotic disorders that are not suitable for adequate follow-up
* women who are pregnant or breast-feeding

Primary outcomes:
measure: safety
timeFrame: during fluoropyrimidine treatment of the patient
Secondary outcomes:
measure: cost-effectiveness
timeFrame: during fluoropyrimidine treatment of the patient
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
city: Amsterdam
country: Netherlands
facility: Slotervaart Hospital
city: Nijmegen
country: Netherlands
facility: Canisius Wilhelmina Hospital
Study officials:
affiliation: Netherlands Cancer Institute, Amsterdam, the Netherlands
name: Jan HM Schellens, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Meulendijks D, van Hasselt JGC, Huitema ADR, van Tinteren H, Deenen MJ, Beijnen JH, Cats A, Schellens JHM. Renal function, body surface area, and age are associated with risk of early-onset fluoropyrimidine-associated toxicity in patients treated with capecitabine-based anticancer regimens in daily clinical care. Eur J Cancer. 2016 Feb;54:120-130. doi: 10.1016/j.ejca.2015.10.013. Epub 2016 Jan 4.
citation: Deenen MJ, Meulendijks D, Cats A, Sechterberger MK, Severens JL, Boot H, Smits PH, Rosing H, Mandigers CM, Soesan M, Beijnen JH, Schellens JH. Upfront Genotyping of DPYD*2A to Individualize Fluoropyrimidine Therapy: A Safety and Cost Analysis. J Clin Oncol. 2016 Jan 20;34(3):227-34. doi: 10.1200/JCO.2015.63.1325. Epub 2015 Nov 16.