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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00838370
Recruitment Status : Completed
First Posted : February 6, 2009
Last Update Posted : March 4, 2014
Information provided by:
The Netherlands Cancer Institute

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.

Condition or disease Intervention/treatment Phase
Neoplasms Drug: Capecitabine, 5-fluorouracil Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Pharmacogenomic and Pharmacokinetic Safety and Cost-saving Analysis in Patients Treated With Fluoropyrimidines
Study Start Date : May 2007
Actual Primary Completion Date : October 2011
Actual Study Completion Date : October 2011

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: DPYD*2A
Patients are screened for a DPD-deficiency. Patients with a DPYD*2A mutation are eligible for intervention with capecitabine/5-FU .
Drug: Capecitabine, 5-fluorouracil

Patients to treat with capecitabine/5-FU will be screened prior to start of therapy for DPYD*2A. Patients heterozygous or homozygous mutant for DPYD*2A receive dose reductions of capecitabine/5-FU of at least 50% in the first two courses. In case this dose is tolerated well, doses will be increased.

In addition, the pharmacokinetics of capecitabine/5-FU and their metabolites will be assessed in these patients.

Other Names:
  • Xeloda
  • Capecitabine
  • Fluorouracil
  • 5-Fluorouracil
  • 5-FU

Primary Outcome Measures :
  1. safety [ Time Frame: during fluoropyrimidine treatment of the patient ]

Secondary Outcome Measures :
  1. cost-effectiveness [ Time Frame: during fluoropyrimidine treatment of the patient ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00838370

Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
Amsterdam, Netherlands, 1066CX
Slotervaart Hospital
Amsterdam, Netherlands, 1066
Canisius Wilhelmina Hospital
Nijmegen, Netherlands, 6532SZ
Sponsors and Collaborators
The Netherlands Cancer Institute
Principal Investigator: Jan HM Schellens, MD, PhD Netherlands Cancer Institute, Amsterdam, the Netherlands

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Prof. dr. J.H.M. Schellens, The Netherlands Cancer Institute Identifier: NCT00838370     History of Changes
Other Study ID Numbers: NKI-AVL_M07PFU
First Posted: February 6, 2009    Key Record Dates
Last Update Posted: March 4, 2014
Last Verified: March 2014

Keywords provided by The Netherlands Cancer Institute:
cost-benefit analysis
antineoplastic drugs
Dihydropyrimidine Dehydrogenase

Additional relevant MeSH terms:
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs