The population of patients over 65 years old is rapidly expanding due to a significantly improving life expectancy globally. Since cancer disproportionately strikes this age group, oncologists, whether community-based or academically oriented, will face a growing population of geriatric cancer patients. Among those affected, colorectal cancer is the second leading cause of cancer-related death, with a median age at diagnosis of approximately 72 years. Life expectancy among older individuals is considerable, as shown for US women in Table 1.[2,3] A 75-year-old woman, for example, has a life expectancy of 12 years if she is healthy and would have a life expectancy of 7 years even if she had significant illness. Therefore, issues concerning adjuvant therapy, prolongation of the disease-free interval, and chronic toxicity are also important for the elderly.
Major concerns in the care of geriatric cancer patients include:
(1) Comorbidities. This population is extremely heterogeneous. Patients can vary from very fit to not being able to live independently due to comorbidities.
(2) Aging process. Aging is a gradual diminution in physiologic reserve or functional capacity over time. Because of this process, geriatric cancer patients with significant comorbidity may not tolerate chemotherapy as well as their younger counterparts. That said, older fit patients usually do not experience increased toxicity.
(3) Limited clinical trial data for geriatric cancer patients. Despite rapid progression in the treatment of colorectal cancer in recent years, dedicated clinical trials for geriatric cancer patients are limited. The median age for all landmark studies of clinical treatment for various stages of colorectal cancer is younger than 65 years of age. Many reports have confirmed the fact that smaller proportions of older cancer patients are referred for clinical trials.
In this article, we will review aspects of the treatment of colon cancer in geriatric cancer patients based on published clinical data specific for geriatric patients.
Physiologic Aspects of Aging
Before discussing chemotherapeutic options, the first step in evaluating older colorectal cancer patients is to better understand the physiologic aging process and its impact on chemotherapy and its toxicity. This diminution of functional reserve or capacity assumes great clinical significance when the organ system is being challenged by cancer and its treatment. The loss of functional reserve is often quite variable during aging. It is also difficult to predict the individual patient's tolerance of cancer treatment. Physiologic changes in functional reserve affect not only the choice of chemotherapeutic agent, but more importantly, the tolerance of side effects of therapy. These physiologic changes can involve all systems and organs (Tables 2 and 3).
Toxicities related to chemotherapy for colorectal cancer mostly affect the gastrointestinal tract, renal function, and peripheral nervous systems. Gastrointestinal mucosal protective mechanisms and the ability for self-repair decrease with age. The secretion of bicarbonate is decreased, with subsequent decreased buffer function. Due to renal function changes and the effect of drug toxicity in the kidneys, geriatric cancer patients are at higher risk of volume depletion and prerenal azotemia.[11,12] Clearly, the treatment of geriatric patients with chemotherapy is complex and unpredictable.
In evaluating renal function, 24-hour urine assays can be used as a way of estimating creatinine clearance. However, this approach is often misleading, as serum creatinine does not reliably reflect renal function.[13,14] The widely used Cockcroft-Gault equation has been shown to underestimate creatinine clearance in geriatric patients because reduced muscle use may lead to a decrease of creatinine production. This equation was derived from a dataset of 249 men, all of whom were inpatients at a veterans' hospital. The patients ranged in age from 18 to 92 (mean age: 57 years) and 59 (24%) were > 70 years old. The formula was derived using 24-hour creatinine clearance values as the standard. Although no females were used in the dataset, the Cockroft-Gault method assumes a reduction in glomerular filtration rate of 15% for this population. Various formulae have been proposed as potential alternatives.[17,18]