Summary and Review Criteria
Determining the correct dosage for the majority of traditional chemotherapeutic agents presents a challenge because most drugs have a narrow therapeutic index, which results in a fine balance between doses that cause significant drug toxicity and loss of efficacy. Dosing calculations for most agents use the patient's body surface area, a method that correlates poorly with drug pharmacokinetics. Genetic differences in drug-metabolizing enzymes are being evaluated in an effort to explain the pharmacokinetic and pharmacodynamic variability seen with many chemotherapeutic agents. Elucidation of the underlying reasons for this variability will enable individualization of therapy to minimize toxicity and maximize efficacy, and thus improve control over the narrow therapeutic index of these agents. Such investigations have led to Clinical Pharmacology FDA Subcommittee recommendations for changes to drug package instructions. This Review discusses the current limitations of body-surface-area-based dosing, examples of successful pharmacogenomic investigations that have used drug-metabolizing enzymes to decrease drug toxicity and/or improve efficacy, and the future promises of pharmacogenomic-directed pharmacotherapy.
Articles were identified by searching the PubMed database for relevant publications written in English from 1966 until 1 September 2008. Abstracts from ASCO published until June 2008 were also reviewed. The search terms included "anticancer drugs", "pharmacogenomics", "pharmacokinetics", and "pharmacodynamics". Studies from the identified literature were chosen based on the best clinical evidence that addressed this article's objectives. Results of data analysis performed by the authors are also included.
Nat Clin Pract Oncol. 2009;6(3):153-162. © 2009
Nature Publishing Group
Cite this: Pharmacogenomic Progress in Individualized Dosing of Key Drugs for Cancer Patients - Medscape - Mar 01, 2009.