Pharmacokinetics of Chemotherapy in the Older Patient
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.
Cancer is a disease that mostly afflicts older individuals, with approximately 60% of cancer morbidity and 70% of cancer mortality occurring in patients over 65 years of age. This age group is growing rapidly; by the year 2030, 1 in 5 Americans will be over 65 years of age. Despite these demographics, older patients have been underrepresented in cancer clinical trials. As a result, our knowledge regarding drug dosing and treatment efficacy is primarily derived from data acquired in a younger cohort of patients.
Both physicians and patients have concerns regarding the side effects of cancer therapy in the older patient. The data on chemotherapy tolerance in older patients in clinical trials are conflicting. Some studies report increased toxicity in older patients, while other studies report equivalent tolerability of chemotherapy in older and younger patients. These differences may reflect disparities in clinical trial eligibility or the heterogeneity in terms of comorbidity, functional status, or other parameters of the older population that enrolled in the trials. Only a few studies have addressed tolerance to cancer therapy in the frail older patient, in older patients with organ dysfunction, or in those with poor performance status. Because of the underrepresentation of these patients on clinical trials, oncologists are left with little to guide them in terms of optimal chemotherapy selection and dosing in the older patient.
Investigators are studying differences in the pharmacokinetics of chemotherapy in relation to age. In particular, they are seeking to determine if they can use pharmacokinetics or other parameters to predict who is at risk for chemotherapy-associated complications. This review focuses on studies of chemotherapy drugs that are commonly prescribed in older patients with cancer and the available data from pharmacokinetics studies relating to older patients. In addition, we review the physiologic changes with aging that might affect chemotherapy tolerance.
Abstract and Introduction
Abstract
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.
Introduction
Cancer is a disease that mostly afflicts older individuals, with approximately 60% of cancer morbidity and 70% of cancer mortality occurring in patients over 65 years of age. This age group is growing rapidly; by the year 2030, 1 in 5 Americans will be over 65 years of age. Despite these demographics, older patients have been underrepresented in cancer clinical trials. As a result, our knowledge regarding drug dosing and treatment efficacy is primarily derived from data acquired in a younger cohort of patients.
Both physicians and patients have concerns regarding the side effects of cancer therapy in the older patient. The data on chemotherapy tolerance in older patients in clinical trials are conflicting. Some studies report increased toxicity in older patients, while other studies report equivalent tolerability of chemotherapy in older and younger patients. These differences may reflect disparities in clinical trial eligibility or the heterogeneity in terms of comorbidity, functional status, or other parameters of the older population that enrolled in the trials. Only a few studies have addressed tolerance to cancer therapy in the frail older patient, in older patients with organ dysfunction, or in those with poor performance status. Because of the underrepresentation of these patients on clinical trials, oncologists are left with little to guide them in terms of optimal chemotherapy selection and dosing in the older patient.
Investigators are studying differences in the pharmacokinetics of chemotherapy in relation to age. In particular, they are seeking to determine if they can use pharmacokinetics or other parameters to predict who is at risk for chemotherapy-associated complications. This review focuses on studies of chemotherapy drugs that are commonly prescribed in older patients with cancer and the available data from pharmacokinetics studies relating to older patients. In addition, we review the physiologic changes with aging that might affect chemotherapy tolerance.
