2007

Clinical Trials Specific to Elderly Patients With Cancer: Fewer Adverse Effects, Similar Outcomes

Points to Remember

• Patients aged 65 years or older are sometimes excluded from clinical trials of cancer chemotherapies because of concerns about poor tolerance and response.
• Mayo Clinic is actively recruiting elderly patients for elderly-specific clinical trials of cancer chemotherapeutic agents.
• Preliminary data suggest elderly-specific chemotherapy clinical trials can limit adverse effects while offering survival outcomes fairly comparable to those in other age groups, especially with treatment modifications such as administering smaller doses more frequently.

The Challenge

The medical oncology literature has documented age discrimination in the treatment of cancer patients aged 65 years or older. Data indicate that elderly patients tend not to get the same clinical
work-up and treatment as younger patients, including the opportunity to enroll in clinical trials evaluating chemotherapeutic agents.

Exclusion of elderly patients from clinical trials compromises care for a growing number of patients. The number of patients aged 85 years or older with newly diagnosed cancer is expected to quadruple by 2050. The National Cancer Institute actively encourages trials to be conducted with older patients because data from these trials can be used to improve care for a patient population that constitutes a steadily increasing proportion of most general practitioners' clinical practices.

Few institutions have responded to the call for greater involvement in elderly-specific clinical trials. Mayo Clinic is among the institutions conducting elderly-specific chemotherapy trials.

A New Approach

In 2005, Mayo Clinic medical oncologists reported findings from a pooled analysis of North Central Cancer Treatment Group comparative clinical trial data. The data, gathered between 1998 and 2000 in patients with non-small cell lung cancer, compared results from trials specific to elderly patients versus trials in which patient age was not a specific criterion for enrollment. In both groups, all cases of lung cancer were confirmed by biopsy as an eligibility criterion. In addition, none of the patients had undergone previous chemotherapy or radiotherapy or had evidence of metastatic disease.

Although the data are preliminary, in general, the Mayo Clinic analysis suggests that elderly-specific clinical trials of cancer patients can be justified because of the lower rates of severe adverse events in the elderly-only trials, with survival equal to that in trials of other age groups. Effectiveness in elderly-only chemotherapy trials may be attributable to the use of treatment modifications such as giving smaller doses more frequently.

Mayo Clinic medical oncologists encourage further research in this area with the goal of clarifying the role of elderly-specific trials in providing — and helping to define — optimal cancer therapy in the elderly. Other issues related to elderly cancer patients also merit further attention. These include an analysis of the types of social support these patients have and the effects of family and social infrastructure on ease of obtaining and complying with cancer chemotherapy.

The Mayo Clinic analysis of North Central Cancer Treatment Group data (1998-2000) compared results from patients enrolled in elderly-specific trials (118 patients older than 65 years) with patients enrolled in age-unspecified clinical trials (108 patients older than 18 years). All patients had non-small cell lung cancer. Preliminary results suggest the following:

• Limiting enrollment to older patients tends to attract much older patients — patients in their 80s and 90s. In the elderly-specific trial, 17% of enrollees were older than 80 years, compared with 3% in the non-age-specific trial. Mayo Clinic medical oncologists interpret this finding to mean that, as the US population ages, performing age-segregated clinical trials offers a means of improving care for the very elderly.
• Survival outcomes show that patients enrolled in the elderly-specific trials had outcomes equal to patients in the non-age-specific trials — despite the fact that oftentimes the very elderly had very advanced disease.
• In terms of tolerating chemotherapy, data suggest that modifying the standard dose schedule by giving smaller doses more frequently is helpful. Despite a general perception that elderly patients do not do well with orally administered therapies, the Mayo Clinic data support the use of oral therapies in elderly patients, showing these patients are very compliant and respond well to it.
• In terms of adverse effects, the elderly fared better on trials specifically designed for them, experiencing lower rates of severe adverse events. This is possibly explained by the fact that therapies were designed to be gentler by reducing doses and increasing frequency of medication.