Dr. Balducci's review, "Management of Cancer in the Elderly" is timely and very appropriate for the journal ONCOLOGY's 20th Anniversary Series, particularly as the US population ages and the percentage of cancer patients over the age of 65 grows. As a critical spokesperson for this important issue, Dr. Balducci has, to a great extent, assumed the mantle of leadership in generating an improved clinical understanding of geriatric oncology as it applies to clinical practice. In this sense, he is standing on the shoulders of perhaps the greatest spokesperson for cancer care of the elderly, B.J. Kennedy, MD.

As a trainee in Dr. Kennedy's medical oncology program in the mid-1960s, the senior author of this editorial commentary (Paul F. Engstrom, MD) was indoctrinated not only with a passion for medical oncology as a profession (rather than a chemotherapeutic technology), but also with the need to treat each cancer patient as an individual, learning to tailor treatment to the chief complaint and the unique needs of each patient. As B.J. frequently reminded us, "we are not chemotherapists; we are oncologists." When he assumed the presidency of the American Society of Clinical Oncology, he dedicated his tenure to the research and treatment of cancer in elderly patients.

Need for Research

Two key issues that Balducci addresses—the incidence of cancer in the aging population and the biology of cancer in the older patient—raise the need to increase our research in this fascinating area. The National Cancer Institute and the National Institute for Aging recently issued P20 grants to several cancer centers to establish cancer research programs directed toward the older patient. These transdisciplinary research programs will encourage investigators to focus on the biology of cancer in the elderly, the epidemiology and distribution of elderly cancer patients, psychosocial issues as they relate to quality of life in elderly patients, the pharmacokinetics of chemotherapy agents in elderly subjects, and the effect of cancer on the surviving spouse or partner as well as the extended family.

Tailored Assessment and Management

Balducci has provided a useful summary defining the nature of older patients and elucidating their special needs. He has emphasized the need for comprehensive geriatric assessment, or some distilled version of it, and he reviews the intriguing observation that cytokines and other biomarkers such as interleukin-6 and D-dimer concentration in the circulation may be predictors of mortality and functional dependency in elderly populations. Clearly, the practicing oncologist needs a workable definition and a user-friendly assessment tool to categorize patients in his/her practice. If relatively mundane markers can be utilized to predict the risks and benefits of treatment, this will indeed be a useful tool in geriatric oncology.

Balducci also provides a review of the management of cancer in older persons, emphasizing the need for dose reductions based on pharmacokinetics, especially volume of distribution based on glomerular filtration rates. Additionally, he discusses multidrug resistance and the heightened normal-tissue susceptibility in the elderly to the toxic effects of chemotherapy drugs.

Clinical Trials

The experience with lung cancer is emblematic of the experience in older patients. Langer et al have summarized the issues confronting elderly individuals with non-small-cell lung cancer (NSCLC). He points out that the majority of patients with NSCLC are diagnosed at age 70 or higher, although this age cohort is underrepresented in national clinical trials—a trend observed in a variety of advanced solid tumors.[1] This underrepresentation may be due to therapeutic nihilism, a lack of confidence that treatment will help, explicit exclusions in trials, misperceptions that increased age automatically equates increased vulnerability to therapy, as well as a true increase in comorbidity, frailty, and vulnerability.

While retrospective analyses have demonstrated the feasibility of standard platinum-based combinations, especially in fit individuals, toxicity—particularly myelosuppression and fatigue— tends to be worse in the elderly compared to younger patients.[2-4] To date, there are no phase III trials in this age group showing a survival advantage for platinum or non-platinum combinations vs the constituent single agents. A large body of work, however, clearly shows that single-agent therapy is superior to best supportive care, with a clear-cut improvement in time to progression, survival, and quality of life, and no clear indication that nonplatinum combinations perform better than the constituent single agents.[5,6]