Predicting toxicity in older patients receiving chemotherapy is an important clinical problem. It has been shown that standard oncology measures such as performance status are not adequate to predict outcomes in the elderly. Clinical measures that are important in geriatric oncology are not routinely assessed in clinical practice. In addition, the objective database for making clinical decisions in older patients is inadequate. Older patients are underrepresented in clinical trials, and when they are included, they do not represent the general population of older patients; those in clinical trials tend to have less comorbidity and better performance status and rarely are over 80 years of age.
Easily Measured Geriatric Parameters
The study by Aparicio et al1 makes a valuable contribution to the care of older patients. The strengths of the study are that it was designed specifically for older patients (median age of 80 years, with patients up to age 91), evaluated treatment of a common malignancy, and most important, included easily measured geriatric parameters.
The formal geriatric assessment performed by geriatricians requires a specialized expertise, is multidisciplinary and time-consuming, and has not been shown to be predictive of treatment toxicity and other outcomes such as ability to complete therapy or relapse-free or overall survival. In the Aparicio et al study, two easily obtained parameters—the Mini-Mental State Examination and Instrumental Activities of Daily Living—were predictive of severe toxicity or unexpected hospitalization.
Further, in the trial, which included a fluoropyrimidine-irinotecan combination, the multiagent chemotherapy arm was also predictive of severe toxicity. The latter finding emphasizes that when administering a palliative regimen, extreme care must be taken to avoid toxicity. The effect of grade 3 or greater toxicity on an older patient can be devastating and can negate any small benefit that the chemotherapy regimen may provide.
The results of the Aparicio et al analysis confirm the findings of a prospective evaluation in the Cancer and Aging Research Group trial.2 That study showed that severe toxicity can be predicted from simply obtained clinical factors; the predictive model that was developed included age greater than 71 years, polychemotherapy, creatinine clearance < 35 mL/min, hemoglobin < 11 g/dL, decreased hearing, falls, social isolation, limited activity, and deficiency in Instrumental Activities of Daily Life. A study by Extermann et al3 also demonstrated that chemotherapy toxicity can be predicted in an older population using Instrumental Activities of Daily Life and other easily obtained clinical information.
Additional Vital Sign
These studies demonstrate that some form of geriatric assessment should be performed in older patients to aid in clinical decision-making. This is particularly important in the palliative setting, when goals such as quality of life, maintenance of independence, and avoidance of toxicity are paramount. It is not acceptable to say that such evaluation is too time-consuming or not helpful.
Most of the data needed for assessment are obtained via patient self-assessment with minimal time expenditure for the clinical staff. This methodology has been validated in a number of settings. The inclusion of geriatric parameters should be thought of as an additional vital sign, along with blood pressure, pulse, and temperature.
Newly Designed Trials
The aging of the population requires changes in the design of clinical trials.4 Elderly-specific trials are important but may be difficult to implement and accrue, particularly in less common malignancies. In those situations where older patients constitute a large proportion of the cancer population, eligibility requirements must take into account the particular issues of older patients to make the results meaningful.
Testing requirements should be realistic in terms of time commitments for patients and caregivers. Toxicity evaluation should be amended to include functional impairments. Outcomes need to include loss of independence. A geriatric assessment should be incorporated in the initial study design so that longitudinal evaluations can be performed to help refine the predictive value of the assessment and better determine risks of chronic toxicities and impairments. Clinical trial reporting also needs to be more descriptive of the outcomes relevant to the elderly.5
Older patients need to be included in phase I trials, since they will ultimately be the consumers of the drugs being tested; geriatric assessment thus needs to be incorporated into the design of phase I trials. Such assessment also needs to be incorporated into the design of studies of biologic therapies, since there may be differences in toxicity risks compared to chemotherapy in older patients.
Older cancer patients need to be a focus of our endeavors. They deserve nothing less. ■
Dr. Lichtman is Attending Physician, 65+ Clinical Geriatrics Program, Memorial Sloan-Kettering Cancer Center, and Professor of Medicine, Weill Cornell Medical College, New York.
Disclosure: Dr. Lichtman reported no potential conflicts of interest.
References
1. Aparicio T, Jouve JL, Teillet L, et al: Geriatric factors predict chemotherapy feasibility: Ancillary results of FFCD 2001-02 phase III study in first-line chemotherapy for metastatic colorectal cancer in elderly patients. J Clin Oncol 31:1464-1470, 2013.
2. Hurria A, Togawa K, Mohile SG, et al: Predicting chemotherapy toxicity in older adults with cancer: A prospective multicenter study. J Clin Oncol 29:3457-3465, 2011.
3. Extermann M, Boler I, Reich RR, et al: Predicting the risk of chemotherapy toxicity in older patients: The Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score. Cancer 118:3377-3386, 2012.
4. Lichtman SM: Clinical trial design in older adults with cancer—the need for new paradigms. J Geriatr Oncol 3:368-375, 2012.
5. Lichtman SM: Call for changes in clinical trial reporting of older patients with cancer. J Clin Oncol 30:893-894, 2012.
