Clinical pharmacology of cancer therapies in older adults

Abstract

This abbreviated review outlines the physiologic changes associated with aging, and examines how these changes may affect the pharmacokinetics and pharmacodynamics of anticancer therapies. We also provide an overview of studies that have been conducted evaluating the pharmacology of anticancer therapies in older adults, and issue a call for further research. (Yancik and Ries, 2000). As the general population ages and life expectancy increases, the number of older adults with cancer is growing.Several unique challenges arise in caring for older adults with cancer. In particular, the physiologic changes associated with aging can have an impact on the pharmacokinetics and pharmacodynamics of cancer therapies. The effects of these age-related changes on drug dosing and tolerance have been understudied, as clinical trials that set the standards for oncology care and drug approval have typically focused on a younger patient population (Hutchins et al, 1999;Talarico et al, 2004). Few studies have included patients who are frail or who have a poor performance status (Table 1).In this review, we provide an overview of the physiologic changes that accompany aging that may have an impact on the pharmacology of anticancer therapies. We also discuss recent studies evaluating the pharmacology of anticancer therapies in older adults. PHYSIOLOGIC CHANGES WITH AGINGAging is a heterogenous process; however, some characteristic changes in physiology and organ function can have an impact on the pharmacology of anticancer therapy. For example, age-related changes in the gastrointestinal tract may affect drug absorption. These changes include a decrease in splanchnic blood flow, gastrointestinal motility, secretion of digestive enzymes, and mucosal atrophy (Yuen, 1990;Baker and Grochow, 1997). With increasing age, hepatic mass decreases and there is a decrease in the cytochrome p450 content in liver biopsies, although the impact of these declines on hepatic function remains controversial (Sotaniemi et al, 1997;Shah, 2004;Sawhney et al, 2005).There is a decrease in renal mass and renal blood flow with aging (Vestal, 1997). These age-related changes in renal function could affect the pharmacology of anticancer drugs. A serum creatinine is often used to approximate renal function in younger adults; however, it is a poor indicator of renal function in older adults because of a decrease in muscle mass with age (FehrmanEkholm and Skeppholm, 2004). On average, the glomerular filtration rate decreases by approximately 0.75 ml min À1 year À1

The Influence of Various Parameters on the Success of Sensor-Controlled Scalp Cooling in Preventing Chemotherapy-Induced Alopecia

“…Agerelated pharmacokinetic and pharmacodynamic changes can lead to increased organ toxicity and therefore enhanced defluvium capillorum [24]. For doxorubicin and weekly application of taxane, an age-related lower renal clearance was found [24].…”

Safety and efficacy of S-1 monotherapy in elderly patients with advanced gastric cancer

“…It still remains under debate whether standard chemotherapies established by pivotal phase III trials might also be applicable to elderly patients with advanced gastric cancer [20][21][22][23]. Lee et al [24] conducted a randomized phase II study comparing capecitabine and S-1 in patients older than 65 years, and showed satisfactory effi cacy of S-1 (RR, 29%; median time to progression, 4.2 months; median OS, 8.1 months).…”

“…The kidney is a very common route for the excretion of drugs; however, it is reported that the glomerular fi ltration rate generally decreases by approximately 0.75 ml/min per year after the age of 40, on average [26]. In several pharmacokinetic studies of chemotherapeutic drugs, such as paclitaxel, vinorelbine, etoposide, cisplatin, and doxorubicin, an age-related decrease in creatinine clearance has been reported [23].…”

Variability in bioavailability of small molecular tyrosine kinase inhibitors

“…Gastric motility slows down and the secretion of gastric juices decreases [126]. Cancer is generally considered to be a disease of the elderly, with 60% of the diagnoses of cancer taking place in patients aged 75 and over [127]. Although age-induced F alterations seem possible, literature and registration texts do not report the necessity of adjusting the dose of smTKIs for the elderly [11][12][13].…”