Co-morbidity is a better predictor of 5-fluorouracil pharmacokinetic than chronological age in older adults

Abstract

9038 Background: Fifty percent of all cancers occur in elderly people and the total cancer burden is expected to rise. Data are needed to ensure the safe administration of chemotherapy in the older patient population. Aging can affect the pharmacokinetics in a number of ways and the selection of chemotherapy in the elderly is frequently and empirically determined by degree of comorbidity and the patients’ functional status. The aim of our study was to determine whether high level of comorbidity, measured using a standardized instrument, can predict 5-fluorouracil (5FU) disposition in older adults. Methods: Geriatric outpatients affected by stage 2 or 3 colorectal cancer and treated with adjuvant MAYO Clinic regimen were the study population. The evaluation was conducted on men aged 70 years old or more, with varying levels of chronic illness. All of them had a good performance status (ECOG score= 0–1). Non neoplastic disease burden was measured using the Cumulative Illness Rating Scale (CIRS) and drug disposition using area under the curve (AUC) of the drug plasma levels during 30 min immediately after 2 minute bolus administration of 5FU 375–425 mg/mq. Results: Forty men were studied, aged between 70 and 80 years old (median = 72); their CIRS scores ranged between 0 and 12 (median=3). Pharmacokinetic analysis confirmed an elevated interpatient variability: 5FU plasma AUC after bolus administration ranged between 241 and 1,140 mg × min/L. There was no correlation between age and comorbidity burden or age and 5FU AUC in that population. On the contrary with increasing comorbidity (increase in CIRS score) there was a proportional increase in 5FU AUC: patients with CIRS score from 0 to 3 (n=22), between 4 and 7 (n=11) and greater than 7 (n=7) had mean AUC of 523.5± 139.6, 637.0±124.0 and 877.4±195.0 mg × min/L respectively (p<0.0001). Conclusions: This study shows that chronological age did nor correlate with CIRS score or 5FU disposition. In older adults with varying degrees of chronic illness, administrated with the same chemotherapy doses, the comorbidity level influenced the magnitude of 5FU exposition, suggesting that the CIRS score could be used to tailor treatment doses. Funded by AIRC-Veneto No significant financial relationships to disclose.