Pharmacology of antineoplastic agents in older cancer patients.

The fastest growing segment of the US population is the group over the age of 65 years. In the next 30 years, this group will comprise over 20% of the population. Because 60% of all cancers occur in this age group, there will be an expected rise in the total cancer burden. Emerging data will better guide the use of chemotherapy in older patients. Studies will be presented discussing the pharmacokinetics of a number of chemotherapeutic agents, with an emphasis on those that have come into use over the past few years. Many of these agents seem to have a beneficial therapeutic index, particularly in regard to elderly patients. There has also been a rising trend in the use of oral chemotherapy. This change was fueled by patient preferences, quality-of-life issues, and the need to decrease the cost of chemotherapy administration. Factors that must be taken into consideration with oral administration of chemotherapy include limitations of the saturability of absorption, patient compliance, and the pharmacokinetic and pharmacodynamic changes that occur in elderly patients. Interpatient variability and drug metabolism, particularly age-related changes in drug metabolism, have been studied. The cytochrome P450 system is particularly important in this context. Safe administration of chemotherapy requires careful attention to the physiologic changes occurring with age and dose adjustments to compensate for end-organ (i.e., renal and hepatic) dysfunction. These adjustments will be discussed for specific drugs. Complementary and alternative therapies will also be presented.

Administration of filgrastim in two patients with drug-induced agranulocytosis.

Two patients experienced agranulocytosis associated with either procainamide or trimethoprim-sulfamethoxazole. Both were treated with filgrastim in an attempt to decrease the duration of agranulocytosis. The first patient received 12 days and the second patient 4 days of filgrastim before white blood cell counts recovered. Published reports both support and refute the efficacy of filgrastim in this setting. The agent may be beneficial in certain cases of this disorder, but further investigation is necessary to determine if it has a definitive role.