Personalizing chemotherapy dosing using pharmacological methods.

ABSTRACT

PURPOSE: Given the toxic nature and narrow therapeutic index of traditional chemotherapeutics, better methods of dose and therapy selection are critical. Pharmacological methods, including pharmacogenomics and pharmacokinetics, offer a practical method to enrich drug exposure, reduce toxicity, and improve quality of life for patients. METHODS: PubMed and key abstracts from the American Society of Clinical Oncology (ASCO) and American Association for Cancer Research (AACR) were searched until July 2015 for clinical data relating to pharmacogenomic- and/or pharmacokinetic-guided dosing of anticancer drugs. RESULTS: Based on the results returned from a thorough search of the literature and the plausibility of utilizing pharmacogenomic and/or pharmacokinetic methods to personalize chemotherapy dosing, we identified several chemotherapeutic agents with the potential for therapy individualization. We highlight the available data, clinical validity, and utility of using pharmacogenomics to personalize therapy for tamoxifen, 5-fluorouracil, mercaptopurine, and irinotecan, in addition to using pharmacokinetics to personalize dosing for 5-fluorouracil, busulfan, methotrexate, taxanes, and topotecan. CONCLUSION: A concerted effort should be made by researchers to further elucidate the role of pharmacological methods in personalizing chemotherapy dosing to optimize the risk-benefit profile. Clinicians should be aware of the clinical validity, utility, and availability of pharmacogenomic- and pharmacokinetic-guided therapies in clinical practice, to ultimately allow optimal dosing for each and every cancer patient.