Pharmacogenetic Testing for tamoxifen, irinotecan, 5-FU, and other cancer medications

Web Seminar: Pharmacogenetics in the Practice of Medicine

Personalized medication management including DNA testing is extremely important for the proper treatment of cancer because finding the right drug and dose is so vitally important. This is not surprising to people that study genetics - research shows that of all the clinical factors such as age, sex, weight, general health and liver function that alter a patient's response to drugs, genetic factors account for a significant proportion.

Over half of all medications including the majority of cancer medications are metabolized by three enzymes in the liver: CYP2D6, CYP2C9, and CYP2C19. Genes are the main factor determining the level of these enzymes - if a person has too much of the enzyme, he processes the medication too quickly, too little of the enzyme and the medication builds up in his bloodstream potentially causing adverse reactions or side effects. Without knowing a patient's genetics, physicians may need to go through months of trial-and-error prescribing to find the right drug and dose.

Population Frequency of Cytochrome P450 (CYP) Metabolizer Types

	Poor (no or low enzyme levels)	Intermediate (reduced enzyme levels)	Extensive (normal enzyme levels)	Ultra-Extensive (high enzyme levels)
CYP2D6	10%	35%	48%	7%
CYP2C9	4%	38%	58%	N/A
CYP2C19	3-21%	24-36%	79-97%	N/A

In addition to cancer medications metabolized by the pathways above, there are specialized test for the following cancer medications:

CYP2D6 for Nolvadex® (tamoxifen)

UGT1A1 for Camptosar (irinotecan)

DPD Enzyme Testing for Fluorouracil (5-FU)

Now you can optimize your patient's response to cancer drugs and many other medications by ordering DNA testing. Results will be entered into our personalized medication management software, GeneMedRx, both the patient and healthcare providers can log in to see if current or future medications are predicted to cause drug-drug or drug-gene interactions so dosage and selection can be catered to the patient's needs. A free 90-day subscription free is included with testing; additional one year extensions are available for a nominal fee. Of course, a patient's DNA never changes so the testing only needs to be done once in a lifetime.

Click here to view a list of drugs for which DNA testing may be helpful.

Ordering Tests

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

http://www.medscape.com/viewarticle/508543_2

Oesterheld, Jessica, M.D. GeneMedRx Drug Metabolism Tables

Aynacioglu AS, et al. Frequency of cytochrome P450 CYP2C9 variants in a Turkish population and functional relevance for phenytoin. Br J Clin Pharmacol 1999; 48(3):409-415

Scordo MG, et al. Genetic polymorphism of cytochrome P450 2C9 in a Caucasian and a black African population. Br J Clin Pharmacol 2001; 52(4):447-450.

Goldstein JA, Ishizaki T, Chiba K, de Morais SM, Bell D, Krahn PM, Evans DA. Frequencies of the defective CYP2C19 alleles responsible for the mephenytoin poor metabolizer phenotype in various Oriental, Caucasian, Saudi Arabian and American black populations. Pharmacogenetics 1997, 7: 59-64

Blaisdell J, et al. Identification and functional characterization of new potentially defective alleles of human CYP2C19. Pharmacogenetics. 2002 Dec;12(9):703-11

Ibeanu GC,  et al. Identification of new human CYP2C19 alleles (CYP2C19*6 and CYP2C19*2B) in a Caucasian poor metabolizer of mephenytoin. J Pharmacol Exp Ther. 1998 Sep;286(3):1490-5.

Ibeanu GC, et al. An additional defective allele, CYP2C19*5, contributes to the S-mephenytoin poor metabolizer phenotype in Caucasians. Pharmacogenetics. 1998 Apr;8(2):129-35.

De Morais SM, Wilkinson GR, Blaisdell J, Nakamura K, Meyer UA, Goldstein JA, The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans. J Biol Chem. 1994 Jun 3;269(22):15419-22

Ferguson RJ, De Morais SM, Benhamou S, Bouchardy C, Blaisdell J, Ibeanu G, Wilkinson GR, Sarich TC, Wright JM, Dayer P, Goldstein JA. A new genetic defect in human CYP2C19: mutation of the initiation codon is responsible for poor metabolism of S-mephenytoin. J Pharmacol Exp Ther. 1998 Jan;284(1):356-61.

Xiao ZS, Goldstein JA, Xie HG, Blaisdell J, Wang W, Jiang CH, Yan FX, He N, Huang SL, Xu ZH, Zhou HH. Differences in the incidence of the CYP2C19 polymorphism affecting the S-mephenytoin phenotype in Chinese Han and Bai populations and identification of a new rare CYP2C19 mutant allele. J Pharmacol Exp Ther. 1997 Apr;281(1):604-9.

Cozza KL, Armstrong SC, Oesterheld JR (2003) Drug Interaction principles for Medical Practice. American Psychiatric Publishing Inc

Werner Schroth; Matthew P. Goetz; Ute Hamann; et al. Association Between CYP2D6 Polymorphisms and Outcomes Among Women With Early Stage Breast Cancer Treated With tamoxifen JAMA. 2009;302(13):1429-1436

Goetz MP et al. The impact of Cytochrome P450 2D6 metabolism in women receiving adjuvant tamoxifen. Breast Cancer Res Treat 2007; 101 (1): 113-21

Borges S et al. Quantitative effect of CYP2D6 genotype and inhibitors on tamoxifen metabolism: implication for optimization of breast cancer treatment. Clin Pharmacol Ther 2006;80(1):61-74

Zhou SF. Polymorphism of human cytochrome P450 2D6 and its clinical significance: Part I. Clin Pharmacokinet. 2009;48(11):689-723

Zanger UM, Raimundo S, Eichelbaum M. Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry. Naunyn Schmiedebergs Arch Pharmacol. 2004 Jan;369(1):23-37

 

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Unless provided information expressly states that is was created by an MD or PharmD or cites another specific source, it was authored by Genelex employees that are not healthcare providers.