July 8, 1998 -- 

Cancer researchers say it is time to correct a significant imbalance between the worlds of cancer treatment and cancer research. As Dr. Frank Haluska of Massachusetts General Hospital puts it: "Approximately half of the cancers that occur, occur in the over-65 age group. There has been a relative lack of concentration on this patient population in clinical trials that have been reported thus far." 

The incidence of cancer clearly rises with age. For example, among women in their early 40's, only one out of more than 840 develops breast cancer each year; but among women in their early 70's, the rate is one of just 215. For prostate cancer, among men in their early 40's, the annual incidence rate is one in 32,000; while among men in their early 70's, it is one of 75. 

However, research on cancer is skewed toward younger participants. At the American Society of Clinical Oncology annual meeting, researchers painted a picture of age discrimination in cancer research. 

Researchers at the Southwest Oncology Group (SWOG), which manages many of the nation's leading cancer trials, compared statistics on their trial participants to cancer rates in the general population according to National Cancer Institute data, looking at gender, race, and age. 

According to their analysis, 43 percent of cancer patients are women; and women made up 41 percent of SWOG trial participants. African-Americans make up about 10 percent of each group. However, while 63 percent of cancer cases are in patients older than 65, elderly patients account for only 25 percent of SWOG trial participants. 

"Whereas women and African-Americans were well represented in SWOG trials, the elderly were substantially underrepresented," says SWOG's Dr. Joseph Unger. "From these results we conclude that the elderly are currently an under-served population in cancer clinical trials. We also conclude that in common cancers, new initiatives to better accommodate the elderly should be considered." 

Part of the problem is money. "Presently these trials are under-funded, they are not supported by Medicare," says Dr. Haluska. "In fact, clinical investigation is difficult to get funded by third-party payers." Since almost all Americans over age 65 are covered by Medicare, that agency's ban on paying for expenses related to experimental treatments seriously impedes the ability of researchers to recruit older participants, the experts say. 

It is not just a matter of paying for an experimental treatment itself, since those direct costs are usually covered by research grants and are not charged to patients. The President-elect of the American Society of Clinical Oncology, Dr. Allen Lichter says, "Medicare, believe it or not, prohibits reimbursements for experimental therapy as part of clinical trials. It not only will deny reimbursement for that therapy, but will deny reimbursement for every part of care, even though that part is not experimental." Dr. Lichter says that policy should be changed. "We think one critical regulatory reform is to ensure that every patient who wants access to a clinical trial can get on it." 

ASCO's current President, Dr. Robert Mayer, points out that increasing the support that insurers give to clinical trials would benefit all patients, not just the elderly. "Participation in clinical trials, for cancer patients, should be a guaranteed right," he says. "We believe that participation in a clinical trial offers excellent, if not the best, type of care that's available. And this remains a major issue for ASCO to continue to assert its influence on in the near future." 

The under-representation of elderly patients in clinical trials not only handicaps research into new therapies, it also creates uncertainty about the proper use of current treatments in older patients. Several trials reported at the American Society of Clinical Oncology annual meeting are aimed at filling in those gaps in information about treatment effects. 

Dr. Elizabeth Dees, of the Johns Hopkins Oncology Center in Baltimore, Maryland says, "Older women with breast cancer are commonly given less aggressive adjuvant treatment than younger women." She says the reasons for the discrepancy include: evidence suggesting that chemotherapy is more toxic to older women and perhaps less effective, the fact that older patients decline aggressive treatment more often, and the absence of adequate clinical trial data on older patients. 

Dr. Dees' group specifically looked at the effects of two common chemotherapy agents, doxorubicin and cyclophosphamide, on 44 women with early stage breast cancers. She says the women over age 65 fared as well as younger patients. "In our small study we found no age-related difference in quality of life, no age-related increase in cardiotoxicity (heart-related problems), and we did see a modest increase in the severity of neutropenia (drops in blood cell counts) with advancing age, but this difference didn't have clinical consequences. So these data then suggest that otherwise-healthy older women with breast cancer should not be excluded from adjuvant chemotherapy with doxorubicin and cyclophosphamide based on their age alone." 

However another study, this one on more than a thousand women in Italy with breast cancer, did find that older patients had more problems with side-effects from chemotherapy. Dr. Diana Crivellari of the Centro di Riferimento Oncologico in Aviano Italy says, "We could show significant differences according to age groups both for patients treated with early and for those treated with delayed chemotherapy, with a uniformly worse tolerance of chemotherapy in the older groups of patients." The most common problems occurred in mucus membranes, such as those lining the mouth and intestinal tract. 

The Italian study used a different combination of chemotherapy drugs than did the Johns Hopkins trial. Along with cyclophosphamide, the Italian patients were given 5-fluorouracil and methotrexate. Massachusetts General's Dr. Haluska says the toxicity of methotrexate might account for the discrepancy between the two breast cancer trials; thus offering doctors a clue on how to tailor adjuvant treatment for older breast cancer patients. 

Another Italian study could give doctors more confidence when they offer chemotherapy to older patients with advanced non-small-cell lung cancer. The study, involving 161 patients, finds vinorelbine treatment clearly benefits patients even when they are older than 70. After one year, 27 percent of patients receiving vinorelbine were still living, compared to only 5 percent of patients receiving best supportive care. 

"Elderly patients with advanced non-small-cell lung cancer can be treated with chemotherapy with this drug, vinorelbine, and they can do this treatment hoping for a survival prolongation and also an advantage in quality of life," according to Dr. Franco Perrone of the Elderly Lung Cancer Vinorelbine Italian Study (ELVIS).