Metastatic Melanoma in the Older Patient

Immunologic Insights and Treatment Outcomes

Upendra P Hegde; Nitya Chakraborty; Bijay Mukherji; Jane M Grant Kels

Disclosures

Expert Rev Pharmacoeconomics Outcomes Res. 2011;11(2):185-193. 

In This Article

Clinical Relevance of Immune-based Treatment of Older Cancer Patients

Aging-associated changes in the immune system have been extensively studied and systematic defects are uniformly recognized in various components of the innate as well as the adaptive immune system.[27–30] Although perceived to be weaker, the aging immune system does have a role to play in older patients and can be harnessed to protect them. This is reflected in the following examples:

  • Administration of active immunization programs directed towards the protection of elderly subjects against bacterial and viral infections have been found to be successful in reducing morbidity and mortality from these infections in the elderly population;[31,32]

  • Although less commonly used in elderly patients owing to concerns of toxicity secondary to the capillary leak syndrome, biological agents such as IL-2 that are intended to stimulate the immune system against immunogenic tumors have been reported to demonstrate clinical benefit when administered in older patients suffering from metastasis from renal cell carcinoma;[33,34]

  • Our review of the literature revealed that the elderly patients with MM also were among those who responded to the immune-based treatments such as tumor vaccines, adoptive immune therapy and anti-cytotoxic T lymphocyte antigen-4 antibody offered to patients with MM in clinical trials;[26,35,36]

  • Finally, studies by Marshall et al. reported that the success of vaccine-based immunotherapy of patients with MM was limited to patients whose pretreatment lymphocytes demonstrated impaired proliferation and deficient secretion of Th1-associated cytokines in response to anti-CD3 stimulation in vitro compared with those who did not have these defects, suggesting a correlation between vaccine-associated correction of lymphocyte function and clinical response in patients.[37]

Unfortunately, little systematic information is published about the success of immune-based treatments of MM for older melanoma patients owing to the relatively small number of geriatric patients with this cancer participating in clinical trials. Furthermore, the currently available treatment options for patients with MM include use of either biological agents, such as IL-2 and IFN-α, and/or chemotherapeutic agents, such as platinum compounds, vinblastine, dacarbazine and taxanes. Elderly patients often decline regimens containing these agents, used either alone or in combination, owing to the significant toxicities and adverse effects these agents are reported to cause on quality of life in relation to to their survival benefit. Furthermore, elderly patients with MM often opt out of treatment, with many stating that they have had a good life and do not want to treat this condition. Also, taking into account the general weaker condition of the elderly patient and probable poor treatment outcome for this disease, physicians do not often recommend aggressive treatment approaches to treat this disease. Finally, a significant proportion of elderly patients are not fit for treatment owing to the presence of active comorbidities, declining cognitive functions and frailty, as well as a lack of family and social support that is necessary to complete such treatment. As a result, fewer elderly patients are accrued in clinical trials that, in turn, has resulted in a lack of knowledge in older patients about the benefits, as well as the toxicities, of the newer treatment approaches used to treat patients with MM. Continued efforts to improve the accrual of eligible elderly patients in clinical trials will help determine whether the benefits seen with these novel agents, including immune-based treatment strategies used for patients with MM, could be extended to elderly melanoma patients.

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