Relation between age and clearance rate of nine investigational anticancer drugs from phase I pharmacokinetic data

Jane M. Borkowski, Mary Duerr, Ross C. Donehower, Eric K. Rowinsky, Tian Ling Chen, David S. Ettinger, Louise B. Grochow

Research output: Contribution to journalArticlepeer-review

Abstract

Aging influences the disposition and effects of several classes of drugs. Although drug clearance rate is correlated with toxicity for many anticancer drugs, few data have been published concerning the relationship of aging and clearance of chemotherapy. This study was performed to identify any relationship between age and clearance rate for anticancer drugs in phase I trials at the Johns Hopkins Oncology Center. In a retrospective study, we examined the clinical and pharmacokinetic data for 344 adults (aged 21-77 years) who received 9 phase I drugs with linear clearance in 13 clinical trials. We sought correlations between age and clearance for each drug and for the whole group. Data available for 9 of the 13 trials were used to compare age (<65 or >65 years) versus dose delivered [< the maximum tolerated dose (MTD) vs ≥ the MTD] or toxicity (< grade 3 vs ≥ grade 3). Of 344 patients, 81 (23.5%) were >65 years old, 34 (9.9%) were ≥70 years old, and 5 (1.5%) were ≥75 years old. There was no significant correlation between drug clearance and age for individual drugs or the group as a whole. There was no significant difference between patients of the older and younger age groups with regard to dose or toxicity. Although only a small number of patients aged ≥75 years were treated, our results suggest that the elderly do not experience greater toxicity even when treated at doses comparable with those given younger patients and should not be excluded from phase I trials on the basis of age. As the population of the United States ages, more elderly patients will be candidates for chemotherapy. A more thorough examination of the relationships between age, clearance rate, and toxicity can be accomplished as active drugs enter phase II/III studies.

Original languageEnglish (US)
Pages (from-to)493-496
Number of pages4
JournalCancer Chemotherapy and Pharmacology
Volume33
Issue number6
DOIs
StatePublished - Nov 1 1994

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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