Development of novel anticancer agents in older patients: pharmacokinetic, pharmacodynamic, and other considerations.
The development of novel anticancer agents in older patients presents both challenges and unique opportunities. Intrapatient variability due to comorbid conditions and the use of multiple concomitant medications may overshadow other age-related differences in pharmacokinetics. The increasing interest in oral agents may be especially problematic in older patients who have difficulty with adherence, particularly if the oral agents are given in combination or according to complex schedules. Polypharmacy, chronic comorbid conditions, and impaired organ reserve in the elderly can lead to pharmacodynamic differences such as increased toxicity and, possibly, reduced efficacy. Hampered immune responsiveness is an important area warranting further research. The development of novel agents to treat older patients with cancer cannot be successfully accomplished without increasing the proportion of elderly patients entered into clinical trials. Furthermore, data obtained from studies in older patients may provide valuable information applicable to the development of novel agents in younger patients and to a better understanding of cancer biology and treatment in general.
Murgo
Anthony J
AJ
National Cancer Institute, National Institutes of Health, Rockville, Maryland 20852, USA. murgoa@mail.nih.gov
Espinoza-Delgado
Igor
I
D000368:Aged / Q000502:physiology; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D015897:Comorbidity; D004341:Drug Evaluation; D015507:Drugs, Investigational / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007107:Immune System / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology
D000970:Antineoplastic Agents; D015507:Drugs, Investigational