Pharmacokinetics of chemotherapy in the older patient.

BACKGROUND The number of individuals aged 65 years and older is growing rapidly, and the majority of cancers are diagnosed in this age group. Age-related changes in physiology can affect chemotherapy pharmacokinetics and pharmacodynamics in older patients. METHODS We review the literature regarding the impact of age on the pharmacokinetics of commonly used chemotherapy drugs and discuss age-related changes in physiology and pharmacology that can affect chemotherapy tolerance in older patients. RESULTS The data on age-related changes in chemotherapy pharmacokinetics are conflicting. While a few studies report age-related differences in chemotherapy pharmacokinetics, most found no significant difference or subtle differences in pharmacokinetics with aging. A difference in pharmacodynamics was commonly seen, however, with older patients at increased risk of myelosuppression and toxicity from age-related decline in organ function. The majority of these studies were performed in a small cohort of patients, thus limiting the generalizability of these results. CONCLUSIONS Additional studies are needed to address the pharmacokinetics and pharmacodynamics of cancer therapies in the older patient. Multicenter pharmacokinetic studies of adequate sample size, which include a thorough evaluation of physiologic factors and geriatric assessment parameters, would provide further insight into the factors affecting treatment tolerance. These studies would also help to guide appropriate chemotherapy dosing and interventions in order to maximize efficacy and minimize toxicity in the older patient.