Camptosar (irinotecan) DNA Drug Reaction Test

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Web Seminar: Pharmacogenetics in the Practice of Medicine

Early in the development of irinotecan, researchers observed that the active metabolite of the drug, SN-38, was cleared from the body through a process called glucuronidation. A gene called UGT1A1 was responsible for sticking that glucoronide group onto the drug. Once glucoronide was on a compound, it was easily excreted by the bile. So, for example, bilirubin and a number of estrogen molecules in the body are glucuronidated. Irinotecan is one of several anticancer drugs that also undergo this process.

Researchers found that a subset of the population, about 10 percent, have a genetic change in the UGT1A1gene that hinders their ability to perform this glucuronidation process. This change does not have an apparent phenotype; it is not something that can be detected by the usual bilirubin test or by some outward manifestation of the patient. However, when patients with the genetic change in UGT1A1, called UGT1A1*28, receive a standard dose of irinotecan, they have a very high risk of severe or even fatal neutropenia, a condition that drastically lowers the ability of the body to fight off infection.

In 2004, the FDA reviewed the data on UGT1A1*28 and decided that this genetic change should be included in insert for irinotecan as a risk factor for severe toxicity.

(TA)6/(TA)6 is the normal genotype: Generally no change in the
administered dose of Camptosar provided that no other agents known to
interact with Camptosar are also administered.

(TA)6/(TA)7 Heterozygous: These patients have intermediate
UGT1A1activity and may be at increased risk for neutropenia; however,
clinical results have been variable and such patients have been shown to
tolerate normal starting doses.

(TA)7/(TA)7 Homozygous: Patients with this genotype should have their
starting dose reduced by at least one level of Camptosar. However, the
precise dose reduction is not known and subsequent dose modifications
should be considered based on individual patient's tolerance to treatment.

The UGT1A1 Camptosar (irinotecan) DNA Drug Reaction Test is considered appropriate for any patient planning to start Camptosar (irinotecan) therapy as people with the variation need lower starting doses.

Now you can add another dimension to providing safer and more efficacious care to your patients by ordering DNA Drug Sensitivity Testing™ for them. Call (800) 523-3080 for more information or to obtain collection kits, or visit how to order for test requisition forms and sample requirements.

REFERENCES

Innocenti F, Undevia SD, Iyer L, et al. Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. J Clin.Oncol. 2004;22:1382-8

Beutler E, Gelbart T, Demina A. Racial variablitiy in the UDP-glucuronosyltransferase 1 (UGT1A1) promoter: a balanced polymorphism for regulation of bilirubiin metabolism? Proc Natl Acad Sci USA 1998;95:8170-4

http://www.rxlist.com/cgi/generic2/irinot_ids.htm