Pharmacology of anticancer drugs in the elderly population

Modifications to bodily functions and physiology are known to occur with age. These changes can have a considerable impact on the pharmacokinetic processes of absorption, distribution, metabolism and excretion and the pharmacodynamic properties of administered drugs. For many drugs with a high therapeutic index, this will be clinically unimportant, but for anticancer drugs, which usually have a low therapeutic index, these pharmacological changes can lead to dramatic consequences, such as excessive drug concentrations and unacceptable toxicity, or subtherapeutic drug concentrations and ineffective treatment. Despite the increased susceptibility of the elderly to these changes, doses are rarely adapted on the basis of pharmacokinetics and pharmacodynamics, with the exception of changes secondary to altered renal function. Until recently, only a few large prospective randomised trials have provided evidence-based data for dose adaptations in elderly patients. However, with increasing knowledge of the pharmacokinetics of anticancer drugs, advances in the knowledge of pharmacokinetic behaviour with aging, and documented efficacy and toxicity data in the elderly population, it is possible to highlight aspects of prescribing anticancer drugs in the elderly. In general, and for most drugs, age itself is not a contraindication to full-dose chemotherapy. The main limiting factors are comorbidity and poor functional status, which may be present in a significant number of the elderly population. Elderly patients with cancer are part of the daily practice of oncologists, but currently clinicians can often only estimate whether dose modification is advantageous for the elderly. This review attempts to elucidate the factors that can influence the pharmacokinetics of anticancer drugs frequently used in the elderly, and the clinical or biochemical parameters that form the basis for dose adjustments with age.