Effects of age on the pharmacokinetics (PK) and pharmacodynamics (PD) of 8 oral anticancer agents from phase I/II trials: A single institution experience

Abstract

2027 Background: In the next 2 decades, 70% of cancers will occur in patients (pts) >70. Aging influences the disposition and effects of several classes of anticancer drugs. Alterations in GI absorption, decline in renal & hepatic clearance and decrease in end-organ functional reserve have been identified in aging population. There have, however, been few studies of the PK and PD of oral anticancer drugs in the elderly pts. Most studies to date have evaluated I.V agents. We are, therefore, performing a study to discern any existing relationships between aging, absorption and clearance rate of investigational oral anticancer agents in clinical evaluation at the Institute for Drug Development. Methods: Demographic data from pts participating in 9 early phase clinical evaluations of 8 oral anticancer agents (shown in table below) is being obtained and stratified according to age (> 65 or 65 years of age are the study set and pts < 65 years serve as controls in each study. Parameters of drug exposure such as area under the concentration-curve (AUC) and clearance and toxicity profiles for each individual agent are being evaluated in the two sets. Results: A total of 251 pts were evaluated. The study set (> 65 yrs) included 67 pts [M 35 /F 32; Median age 70; PS 0–15, PS 1–49, PS 2 -3] and control set included 186 pts [M 76 /F 110; Median age-54; PS 0–50, PS 1- 124, PS 2 - 12]. Tumor types in the Study/ Control sets were Breast (6/ 57), Colorectal (16/ 20), Hepatocellular (5/ 6), NSCLC (13/ 13), Renal (12/ 37), Pancreas (4/ 11) and others (11/ 42). The median number of treatment courses in the Study and Control sets were 3 and 2 respectively. PK/ PD analyses to assess the differences between the two sets is ongoing. Conclusions: Significant disparities in the PK’s of oral anticancer agents are possible in the elderly cancer pts. PK analysis is ongoing. Given the small study set in our evaluation, larger studies are warranted to discern these differences. No significant financial relationships to disclose.