After weighing the evidence, an expert panel recommended a combination of chemotherapy drugs for most women with localized breast cancer. The panel made other recommendations as well, providing broad guidelines on when and how to use adjuvant therapies.
However, one group largely left out of the recommendations was older women. The reason for the omission was simple: Few breast cancer trials have had enough older participants to provide meaningful data on their response to therapy. The panel simply did not have enough information to make recommendations for older women.
The same is true for other cancers. Only 25 percent of clinical trial participants are age 65 or older, according to a 1999 study, even though 63 percent of all cancer patients fall into this age group.
What keeps older patients out of trials? The barriers include health problems other than cancer, such "co-morbidities" as heart disease or poor kidney function. But other barriers are psychological or socioeconomic, according to reports in the literature. Now, clinical researchers and organizations are beginning to tackle some of these roadblocks in an effort to increase the number of older people in trials.
Medicare to pay
Perhaps the most dramatic step so far in reducing barriers has been the White House announcement in June 2000 that Medicare would begin to cover the patient care costs for beneficiaries in clinical trials. Before that, it was Medicare policy not to pay for trial-related patient care costs, such as office visits and tests.
Under the new policy, Medicare will cover patient care costs in clinical trials, including items and services that it normally covers when the care is taking place outside of a trial. It will also pay for the administration of an experimental drug that is being tested in a trial and for supportive care, such as anti-nausea drugs to prevent complications from the experimental drug.
The announcement came after several years of debate, both inside and outside Congress, about insurance and Medicare coverage of trials. In 1999 the Institute of Medicine recommended coverage of all clinical trials, leading to President Clinton's directive.
The Health Care Financing Administration (HCFA), which manages Medicare, has
determined that a trial must meet three broad criteria to be qualified for Medicare coverage.
- The trial has a therapeutic intent (not intended primarily to test for side effects)
- The trial's purpose is within a Medicare benefit category (such as cancer diagnosis and treatment, but not cancer prevention)
- The trial is funded by one of several federal agencies or is conducted under an Investigational New Drug application approved by the Food and Drug
Administration or is exempt from having a IND under FDA regulations.
Some clinical trials are automatically qualified to receive Medicare coverage of their routine costs, other trials may qualify under criteria that are currently in development.
Other barriers to overcome
While removing financial barriers should help more older patients enroll in trials, there are other barriers to overcome as well. One of these may be physician bias -- the assumption that treatment is too hard on older people and that the risk and discomfort will not be worth the benefits. One recent study showed that physicians asked 51 percent of their patients under 65 to participate in clinical trials but only 35 percent of those over 65, according to Margaret Kemeny, M.D., from the State University of New York at Stony Brook. Kemeny, who presented these findings at the May 2000 meeting of the American Society of Clinical Oncololgy (ASCO), added that an equal percentage of younger and older patients agreed to participate once they were asked.
Other data have begun to challenge the assumption that older patients should not or do not want to participate in trials. For example, studies show that older women in good general health -- those having what physicians call "good performance status" -- tolerate standard chemotherapy regimens almost as well as younger women, said Hyman Muss, M.D., a consensus conference speaker.
"If they have good renal (kidney) function and good performance status they do pretty well," said Muss, who is associate director of the Vermont Cancer Center. In fact, some older patients may even find the treatments easier to tolerate than younger patients, he said. "Interestingly enough, older people seem to have less nausea and vomiting, and some have better quality of life than younger patients."
Kemeny, who was one of the consensus panel members, agreed. "A lot of studies have shown that older women can tolerate chemotherapy well if they have good performance status. Their performance status is more important than their age," said Kemeny.
Trials designed for older patients
As the evidence grows that older patients can tolerate chemotherapy and other treatments, research organizations have begun to design clinical trials that focus on this age group. One of these is looking at the effect of radiation therapy on early-stage breast cancer for women over 70 treated with lumpectomy and tamoxifen. This trial has already completed enrollment, according to the principle investigator, Kevin S. Hughes, M.D., at the Lahey Clinic in Burlington, Mass. He said that preliminary results will be presented at ASCO's annual meeting in May 2001.
Two other studies designed specifically for the elderly are planned under an agreement between the National Cancer Institute and the National Institute on Aging. The two NIH institutes have issued joint program announcements, inviting grant applications for research on cancer pharmacology and older patients and elderly women and breast cancer.
One grant has gone to the Cancer and Leukemia Group B, one of the NCI-sponsored Cooperative Clinical Trials Groups (networks of physicians and institutions that conduct trials jointly). The CALGB study will look at the effect of chemotherapy in women over 65 with early-stage breast cancer. The study will test standard chemotherapies against the oral drug, capecitabine, according to Muss who is principal investigator of this trial. Enrollment of patients is expected to begin in early 2001, he said.
Another grant under the joint program is going to another cooperative group, the Southwest Oncology Group (SWOG), to carry out three trials in patients age 70 or older with metastatic disease -- breast, colorectal, and bladder cancer. The trials will look at the efficacy and toxicity of drugs in elderly people, according to Kathy S. Albain, M.D., of Loyola University Medical Center in Maywood, Ill., who is chair of SWOG's Committee on Women and Special Populations. Led by Derek Raghavan, Ph.D., of the University of Southern California in Los Angeles, the investigators will also study the pharmacology of the drugs, Albain said, "since there's almost no data like this for the elderly."