Pharmacogenomic and Pharmacokinetic Safety and Cost-saving Analysis in Patients Treated With Fluoropyrimidines

Netherlands Cancer Institute (NKI)

Status and phase: Completed; Phase 1

Conditions: Neoplasms

Treatments: Drug: Capecitabine, 5-fluorouracil

Study type: Interventional

Funder types: Other

Identifiers

NCT00838370

NKI-AVL_M07PFU

Details and patient eligibility

About

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.

Full 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.

Enrollment: 22 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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22 participants in 1 patient group

DPYD*2A

Experimental group

Description:

Patients are screened for a DPD-deficiency. Patients with a DPYD\*2A mutation are eligible for intervention with capecitabine/5-FU .

Treatment:

Drug: Capecitabine, 5-fluorouracil