Anticancer drug therapy in the older cancer patient: Pharmacology and polypharmacy
Older patients currently are the largest group of oncology patients and their numbers will continue to expand. There has been minimal participation of older patients in clinical trials. This has resulted in a lack of data to make high-level evidence-based decisions with regard to chemotherapy. There has now been a number of clinical trials which have given information with regard to age-related changes and the spectrum of toxicity that occurs with older patients. There is also an expanding literature on organ dysfunction. The overall data seem to indicate that there are a very few age-related changes in the pharmacokinetics of chemotherapy. The small changes that are present have not been clinically significant. It seems that the pattern of toxicity is more reflective of patient selection (functional status, performance status), comorbidity, and drug scheduling. The large number of drugs with significant renal excretion requires careful evaluation of renal function. Future clinical trial design needs to be adapted to older patients. Therefore, drugs, which will be primarily used by older patients, should be studied in older patients. These studies should involve pharmacokinetics, and oral therapies should include measurements of compliance. Phase II trials of new agents should consider prospectively dividing groups of patients by age (i.e., <75 years vs. >or=75 years). Phase I trials should consider accruing older patients. The studies can be performed in the older group by using progressive degrees of functional impairment and increasing comorbidity as a surrogate for dose limiting toxicity. Functional independence as a clinical benefit of cancer treatment in older individuals should be considered as an endpoint. Overall survival may not be an appropriate endpoint in clinical trials in the oldest group. Clinical trials should consider studying long-term functional and medical consequences of cancer treatment in long-term older cancer survivors. Journal editors should encourage the inclusion of age-related analyses in the reporting of clinical trials to provide meaningful information for clinicians caring for older patients. Ideally, the clinical trial design should prospectively incorporate age analysis to maximize clinical benefit of data generated. A careful assessment of medication used in older patients needs to be part of routine evaluation to minimize the adverse effects of polypharmacy.