People over the age of 65 are the fastest growing segment of the UK population. By 2034, their number is projected to rise by 50%,1 when the over-65s will make up more than 20% of the population. This changing demographic has resulted in a >50% cancer incidence in the 50-74 age group; a third of all new cancer diagnoses are in the >75 age group.2 Three-quarters of all cancer deaths occur in the >65 age group and a half of all cancer deaths occur in the >70 age group. While the cancer burden is highest in the older age group, the evidence for systemic anticancer therapy (SACT) comes largely from retrospective and subgroup analyses of prospective clinical trials, and caution should be exercised in extrapolating results to the general older population. The data, however, suggest that SACT can be safe and effective for these patients, although there is a tendency to greater treatment-related morbidity. This chapter will consider the important aspects of SACT prescribing and the clinical data underpinning its use in older people.
General aspects of SACT in older patients
As with all patients, treatment decisions in older patients require expert knowledge of altered drug pharmacology and biology (which is well characterized in breast cancer, for example), the type of therapy (cytotoxic, small molecules, immunotherapy), the expected benefits and the intent of treatment (curative adjuvant therapy or palliative). It is important to individualize therapy, particularly in older patients. Optimal therapy requires characterization of the functional reserve of an individual patient, both physical and mental, assessment of the extent and severity of comorbidity, identification of malnutrition (low albumin, anaemia) and the degree of social support. Treatment decisions have to be made in the context of life expectancy. The expansion of the therapeutic armamentarium with targeted small molecules, monoclonal antibodies and immunotherapy is likely to expand the number of patients it will be possible to treat who would not otherwise have been suitable for traditional cytotoxic therapy. The newer agents, however, have specific toxicities that may make older patients more susceptible to them.
The physiological and pathological decline in hepatic and renal function together with reduced bone marrow reserve associated with ageing are key contributors to the altered pharmacokinetic and pharmacodynamic characteristics of many cancer drugs. This, along with the potential for drug interactions due to the polypharmacy associated with older patients, and factors such as germline mutations in drug-metabolizing enzymes and altered pharmacogenomics, can complicate dosing issues especially for cytotoxic agents with narrow therapeutic ratios. Table 9.1 highlights important age-related physiological changes and their consequences for chemotherapy prescribing. Most pharmacokinetic studies are small and include few older patients. On the whole, most studies show that significant pharmacokinetic changes are based on hepatic and renal function and not on age. Not surprisingly, myelosupression from cytotoxic therapy is more common in older patients. ...