Pharmacogenetics in Clinical Practice

Three major types of evidence are needed to implicate a polymorphism in clinical care: screens of tissues from multiple humans linking the polymorphism to a trait; complementary preclinical functional studies indicating that the polymorphism is plausibly linked with the phenotype; and multiple supportive clinical phenotype/genotype studies. Because of the high probability of error in genotype/phenotype association studies, replication is essential.

Adjusting drug dosages for variables such as renal or liver dysfunction is accepted in drug dosing. Even though there are many examples of significant effects of polymorphisms on drug disposition (e.g., Table 4-2), there is much more hesitation from clinicians to adjust doses based on genetic testing than on indirect clinical measures of renal and liver function. Existing resources permit clinicians to access information on pharmacogenetics (see Table 4-1).

The high frequency of functionally important polymorphisms ensures that dosing complexity will increase. Even if only one polymorphism were considered when dosing a drug, the scale of

Cancer X

Regimens:

Surgery only

LD MTX HD MTX HD MTX LD Paclitaxel HD Paclitaxel HD Paclitaxel

HD Cyclophosphamide

3 drug regimens

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