People 65 years old and greater are a growing segment of society, with predications that this age group will make up approximately 20% of the US population by the year 2030.1,2 The incidence and mortality rates of cancer increases with age, with approximately 50% of all cancers occur in this age group.3 The majority of CRCs occur in patients older than 50.
Aging is an individualized process, and age alone should not be a contraindication to treatment. Physiologic age, not chronologic age, should be considerered in the management of elderly CRC patients. Age-related pharmacodynamic and pharmacokinetic changes and underlying comorbidities may contribute to increased incidence of drug toxicity and diminished tolerability.4 These physiologic changes may alter absorption, metabolism, drug distribution, and excretion.
Pharmacokinetic Considerations in the Aging Patient
- Reduced gastric acid secretion, gastric emptying and gastric motility
- Reduced splanchnic blood flow
- Decreased volume of distribution due to body composition (fat content doubles in the elderly) and intracellular water decrease
Liver size decreases with age
Liver blood flow reduces with age
Decline in P450 (CYP) microsomal system
Data from Skirvin and Lichtman1
Comorbidities prevalent in persons 65 or older may contribute to increased risk of chemotherapy toxicity.5 Health care providers may undertreat elderly patients for a number of reasons, including patient preference, age bias, lack of support systems, and limited data on efficacy/safety in this subset of patients.6
A Comprehensive Geriatric Assessment (CGA) may be useful for estimating physiologic age based on functional reserves, and gross life expectancy and determining treatable conditions that may influence tolerance to treatment.7 Specific factors within this assessment that should be taken into consideration when tailoring a treatment regimen include
- Functional status
- Socioeconomic issues
- Geriatric syndromes
Based on findings following this assessment, older patients are then further classified into 3 groups8
- Functional independent activities of daily living (ADL), such as grooming, dressing, and eating, and instrumental activities of daily living (IADL), such as using transportation, shopping, and managing money
- Intermediate functional impairment
- Major functional impairment and/or complex comorbidity
These findings may assist in guiding treatment recommendations.2
From Balducci,8 with permission
The full CGA may be time consuming; therefore, several brief screening tests are available to assess older patients and determine those who may benefit from a comprehensive assessment (CGA).
- Timed “Up and Go” (TUG test)2
- Rapid screening test (Distress Thermometer)2
- Vulnerable Elders Survey (VES 13)2
Researchers have discovered that levels of interleukin 6 and d-dimer levels circulating in the blood also may be predictive of mortality and functional dependence in individuals 71 or older.9
Over the past decade, newer cytotoxic agents, including capcetabine, irniotecan, and oxaliplatin, have been approved for the treatment of CRC. The use of these agents should not be excluded in the elderly population, based on currently available data that shows similar efficacy between age groups.4 A number of clinical trials have demonstrated that CRC patients 70 or older are able to tolerate adjuvant and palliative 5-FU–based chemotherapy as well as younger patients, with similar efficacy.10-14 Unfortunately, the elderly remain underrepresented in clinical trials, with more information needed to determine impact of comorbidities on tolerance of treatment.15
Guidelines for Senior Adult Oncology
The National Comprehensive Cancer Network (NCCN) have published evidence-based assessment and treatment guidelines for cancer care in the elderly and the Oncology Nursing Society (ONS) and Geriatric Oncology Consortium16 have published a joint position paper on cancer care in older adults.
- Skirvan A, Lichtman S. Pharmacokinetic considerations of oral chemotherapy in elderly patients with cancer. Drugs Aging. 2002;19:25-42.
- National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology, Senior Adult Oncology.v.1.2010. Available at: http://www.nccn.org/professionals/physician_gls/PDF/senior.pdf Accessed December 14, 2010.
- Wasil T, Lichtman S. Treatment of elderly cancer patients with chemotherapy. Cancer Invest. 2005;23:537-547.
- Honecker F, Kohne GH, Bokemeyer C. Colorectal cancer in the elderly. Drugs Aging. 2003;20:1-11
- Repetto L. Greater risks of chemotherapy toxicity in elderly patients with cancer. J Support Oncol. 2003;1(suppl 2):11-17.
- Dale D. Poor prognosis in elderly patients with cancer: the role of bias and undertreatment. J Support Oncol. 2003;1(suppl 2):11-17.
- Rao AV, Seo PH, Cohen HJ. Geriatric assessment and comorbidity. Semin Oncol. 2004;31:149-159.
- Balducci L. Management of cancer in the elderly. Oncology. 2006;20:1-5.
- Cohen HJ, Harris T, Pieper CF. Coagulation and activation of inflammatory pathways in the development of functional decline and mortality in the elderly. Am J Med. 2003;114:180-187.
- Popescu RA, Norman A, Ross PJ, et al. Adjuvant or palliative chemotherapy for colorectal cancer in patients 70 years or older. J Clin Oncol. 1999;17:2412-2418.
- Sargent D, Goldberg R, Jacobson S, et al. A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients. N Engl J Med. 2001;345: 1091-1097.
- de Gramont A, Figer A, Seymour M, et al. Leucovorin and fluorouacil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000;18:2938-2947.
- Folprecht G, Cunningham D, Ross P, et al. Efficacy of 5-flourouracil-based chemotherapy in elderly patients with metastatic colorectal cancer: a pooled analysis of clinical trials. Ann Oncol. 2004;15:1330-1338.
- Goldberg RM, Tabah-Fisch IT, Bleiberg H, et al. Pooled analysis of safety and efficacy of oxaliplatin plus flourouracil/leucovorin administered bimonthly in elderly patients with colorectal cancer. J Clin Oncol. 2006; 24:4085-4090.
- Lewis JH, Kilgore ML, Goldman DP, et al. Participation of patients 65 years of age or older in cancer clinical trials. J Clin Oncol. 2003;21:1383-1389.
- Oncology Nursing Society. Oncology Nursing Society and Geriatric Oncology Consortium joint position on cancer care in the older adult. Oncol Nurs Forum. 2007;31:623-624. Available at: http://ons.metapress.com/content/dp878040421203w1/fulltext.pdf Accessed December 14, 2010.
efficacy—the effectiveness or ability of a drug to control or cure an illness; the maximum ability of a drug or treatment to produce a result regardless of dosage. A drug passes efficacy trials if it is effective at the dose tested and against the illness for which it is prescribed. In the procedure mandated by the FDA, phase 2 clinical trials gauge efficacy, and phase 3 trials confirm it
glomerular filtration rate (GFR)—an indicator of kidney function calculated from the serum creatinine level using the patient’s age, weight, gender, and body size; volume of fluid filtered from the renal glomerular capillaries into Bowman’s capsule per unit of time. Clinically, this is often measured to determine renal function
incidence—the rate of occurrence of new cases of a particular disease in a population being studied
pharmacodynamic—of or relating to the study of the action or effects of drugs on living organisms. It is often summarily stated that pharmacodynamics is the study of what a drug does to the body, whereas pharmacokinetics is the study of what the body does to a drug
pharmacokinetic—of or relating to the study of the bodily absorption, distribution, metabolism, and excretion of drugs. It is often summarily stated that pharmacodynamics is the study of what a drug does to the body, whereas pharmacokinetics is the study of what the body does to a drug
polypharmacy—the practice of administering many different medicines especially concurrently for the treatment of the same disease
splanchnic—of or relating to the viscera; anything belonging to the internal organs of the body, as opposed to its framework