January 24, 2007

Many Breast Cancer Patients Quit Tamoxifen Early

Nearly one-quarter of breast cancer patients stop taking the drug tamoxifen within the first year of a standard five-year regimen, a new Irish study reveals.

Doctors routinely prescribe tamoxifen -- which inhibits estrogen's stimulatory effect on cancer cells -- to patients after breast cancer treatment, to help prevent a recurrence.

But the new study found a steep drop-off in drug adherence, about twice the rate observed in previous studies. Treatment non-adherence rose over time and shifted with patient age, the researchers added.

In fact, the study found that more than one-third of patients ceased taking their medication within three-and-a-half years of treatment. Younger women between 35 and 44, and those over the age of 75, were the most likely to discontinue drug usage.

"We now know that there are a considerable number of women who stop taking their tamoxifen early," said study author Thomas I. Barron, from the department of pharmacology and therapeutics at Trinity College Dublin and St. James's Hospital in Ireland. That's concerning, he said, because "women discontinuing their tamoxifen early may not receive the full benefits of their treatment."

Barron's group believe that the "surprisingly high" lack of adherence stems from the relatively long time women are placed on the drug and its often troublesome side effects.

The findings are published in the Jan. 22 online issue of Cancer, and will appear in the journal's March 1 print edition.

Tamoxifen, a "selective estrogen receptor modulator," is typically prescribed for a five-year period following a diagnosis of breast cancer, although in some cases a longer regimen is recommended. Taking the medication for less than five years can undercut the drug's effectiveness and is associated with more frequent cancer recurrence and, ultimately, a higher risk of death, experts say.

Barron and his colleagues note that about 75 percent of women diagnosed with breast cancer are prescribed a hormonal agent such as tamoxifen as part of their overall treatment. Research suggests that tamoxifen prevents more than 40,000 breast cancer recurrences worldwide each year.

However, side effects that mimic menopausal symptoms are prevalent among some, but not all, women who take the drug. These include hot flashes, vaginal discharge, irregular menstruation, headaches, fatigue, nausea, and vaginal itching and rashing.

To gauge patient adherence with prescribed tamoxifen, Barron and his team reviewed pharmacy database records to examine the prescription-filling habits of more than 2,800 Irish breast cancer patients over the age of 35, all of whom had embarked on a tamoxifen regimen sometime between 2001 and 2004.

The researchers note that all patients received free health services and free medicine, so cost was not an obstacle to continued treatment. None of the patients took any other hormone therapy along with tamoxifen.

Barron and his colleagues found that more than 11 percent of the women stopped taking the medication within 30 days of treatment, a figure that rose to almost 15 percent by 90 days.

The one-year dropout rate was 22 percent and by the second year over 28 percent of the women were off the drug. By 3.5 years that number had risen to just over 35 percent.

Just over a quarter of the women changed their treatment to another hormone therapy within six months of starting tamoxifen. However, these women were defined as treatment "switchers" rather than dropouts.

In total, a little more than 31 percent of the patients continued with tamoxifen as prescribed throughout the study period.

The researchers noted that patients who took antidepressants in the year prior to beginning tamoxifen use appeared more likely to drop out before the five-year protocol was up. The finding was not surprising, they said, given that depression has often been associated with poor drug-taking behavior.

Though no single reason was offered for the high dropout rates, the authors believe that, among the elderly, a drop in social support and an increase in functional impairment might play a role. Younger patients may simply be less willing to put up with side effects and be less accepting of their breast cancer diagnosis overall, relative to more mature women, the researchers said.

Barron pointed out that, due to patient demand and preference, the number of new oral anti-cancer medicines is increasing, and adherence problems regarding tamoxifen might apply to a much broader range of cancer treatments.

"The effectiveness of these new and powerful treatments over the more traditional intravenous chemotherapies depends very much on patients' ability to adhere to treatments," he cautioned.

Barron said patients contemplating the cessation of their tamoxifen regimen due to harsh side effects should talk to their doctors first.

"It may be possible to alleviate any troublesome side effects they are experiencing or, in some cases, alternative hormonal treatment may be available," he said.

Robert Smith, director of cancer screening for the American Cancer Society in Atlanta, seconded the need for continuous physician oversight.

"My impression is that most women are not particularly happy with the side effects, although they experience them at different levels," said Smith. "And five years is a long time to take a drug. So for doctors maintaining the protocol -- making sure the women complete it -- becomes as much a standard of care as prescribing the treatment in the first place."

"This is where powers of persuasion need to be brought to bear," he suggested. "Most people are very trustful of their doctors if there's a good report, and in those cases a doctor's advice could be very powerful. So, based upon the spacing of the follow-up visits, one would hope there would always be a discussion about how the therapy is going. Because this is the opportunity to really try to get them back on track if there's a problem."

A second study published in the same issue of Cancer revealed that for early-stage, elderly breast cancer patients (those over the age of 65) radiation therapy following both a lumpectomy and five years of tamoxifen treatment appears to dramatically reduce both the risk of cancer recurrence and the development of new tumors.

Led by Ann M. Geiger of Wake Forest University Health Sciences in Winston-Salem, N.C., the research team based their conclusions on the experience of more than 1,800 women over the age of 65 who underwent initial surgery between 1990 and 1994.

According to the researchers, the findings support the use of a combination of all three treatments as "standard therapy" for women of all ages, with an exception for those facing an extremely short life expectancy.

No comments: