Bone-Building Drug Zometa vs. Breast Cancer

Zometa Plus Chemo Shrinks Breast Cancer Tumors More Than Chemo Alone

By Charlene Laino
WebMD Health News

Reviewed By Michael W. Smith, MD

Dec. 11, 2008 (San Antonio) -- Adding the bone-building drug Zometa to chemotherapy shrinks breast tumors better than chemo alone, researchers report.

Zometa is currently used to help prevent the bone loss associated with some cancer treatments. "But in the last two years, there's been a suggestion that it may reduce the risk of breast cancer recurrence as well," says Robert Coleman, MD, professor of medical oncology at the University of Sheffield in England.

He and colleagues put the drug to the test in 205 women with breast cancer. Prior to surgery to remove their tumors, half were given chemo and half were given chemo plus Zometa. The study was sponsored by Novartis AG, which makes Zometa.

Tumors shrank to 20.5 millimeters in size in the Zometa group, compared with 30 millimeters in the chemotherapy-alone group. "And even after the analysis took into account other factors that can affect tumor size (such as whether the tumor is fueled by hormones), there was still a better response with Zometa," Coleman tells WebMD.

Also, tumors completely disappeared in 11% of women on Zometa vs. 6% of women given chemo alone.

As a result, fewer women given Zometa required a mastectomy rather than breast-conserving surgery to remove their tumor, he says. About three-fourths of women in the chemotherapy group underwent a mastectomy vs. two-thirds in the combination group.

"This is the first evidence in humans that this drug may have a direct anticancer effect," Coleman says.

Claudine J. Isaacs, MD, director of the breast cancer program at Lombardi Cancer Center in Washington, D.C., says the findings suggest a new use for Zometa in fighting breast cancer.

If confirmed in larger, longer studies, "we should consider giving Zometa for its antitumor effects alone," she tells WebMD.

The research was presented at the annual San Antonio Breast Cancer Symposium.

Aromatase Inhibitors vs. Tamoxifen

Also at the meeting, researchers reported new evidence that postmenopausal women with early breast cancer fare slightly better if they are treated with newer drugs called aromatase inhibitors than if they are given standard hormone therapy.

In one study of nearly 5,000 women, those who were given the aromatase inhibitor Femara were less likely to have their cancer come back, compared with those who were given standard tamoxifen. And there was even a hint that they'd live longer if they opted for Femara.

The study included 4,922 postmenopausal women who were given either tamoxifen or Femara after breast cancer surgery. It was funded by Novartis Pharmaceutical Corp., which makes Femara.

Nearly six years later, Femara lowered the risk of relapse by a significant 12%. Women taking Femara were also 13% less likely to die than those given tamoxifen, but the finding could have been due to chance.

The researchers also studied more than 6,000 women who were given either Femara alone, two years of tamoxifen followed by three years of Femara, or two years of Femara followed by three years of tamoxifen.

By nearly six years after starting treatment, about 13% of women in all three groups relapsed, suggesting that all three are good options, Isaacs says. She was not involved with the work.

Aromatase inhibitors block an enzyme the body uses to make estrogen, thereby almost totally shutting down the body's ability to make estrogen. Tamoxifen also blocks estrogen's effects, but not in the same way as Femara and its sister drugs Aromasin and Arimidex. It blocks estrogen from having an effect on cancer cells, slowing tumor growth.

Aromasin Prevents Recurrences

Another study showed that Aromasin also beats out tamoxifen when it comes to preventing recurrences.

The study involved nearly 10,000 postmenopausal women who were randomly assigned to receive Aromasin or tamoxifen. By nearly three years later, those on Aromasin were 11% less likely to suffer a recurrence or die than those on tamoxifen.

This study "provided the missing link. Other studies have shown that the other two aromatase inhibitors, Arimidex and Femara, are superior to tamoxifen. Now we can say that at least on initial therapy, all the aromatase inhibitors are superior to tamoxifen," says researcher Stephen Jones, MD, medical director of U.S. Oncology Research in Houston.

Other researchers compiled data on nearly 10,000 postmenopausal women with hormone-fueled tumors involved in two studies comparing five years of aromatase inhibitors to five years of tamoxifen. By eight years later, 19.2% of women on tamoxifen relapsed, compared with 15.3% on aromatase inhibitors.

Then the researchers pooled data from four other studies that compared five years of tamoxifen treatment to two to three years of tamoxifen followed by two to three years of an aromatase inhibitor in more than 9,000 women.

By six years later, 12.6% of those who switched to an aromatase inhibitor relapsed vs. 16.1% of those who stayed on tamoxifen.

Importantly, there was also a survival advantage associated with switching: Only 10.8% of these women died, compared with 13.0% of those who stayed on tamoxifen.

While the studies show taking an aromatase inhibitor appears to offer a slight edge over tamoxifen, doctors stress that women who have been prescribed tamoxifen shouldn't panic.

"The important thing is to be on some type of hormone treatment. They're all effective," Isaacs says.

Side effects may enter into the picture, she notes. Tamoxifen is associated with an increased risk of vaginal bleeding, night sweats, and clots in the legs or lungs. But women taking aromatase inhibitors are more prone to slightly elevated cholesterol levels, joint pain, and bone loss than those taking tamoxifen.

The big question remains how to best use the newer drugs, "and here the data are conflicting," Isaacs says. Some of the studies suggest they work best right out of the box, while others suggest women could cut their risk of recurrence even further by taking an aromatase inhibitor after completing several years on tamoxifen.

"We're stilling trying to figure out the optimal sequence and duration of treatment," she says.

SOURCES: 31st Annual CTRC-AACR San Antonio Breast Cancer Symposium, San Antonio, Dec. 10-14, 2008. Robert Coleman, MD, professor of medical oncology, University of Sheffield, England. Claudine J. Isaacs, MD, director of the breast cancer program, Lombardi Cancer Center, Washington, D.C. Stephen Jones, MD, medical director, U.S. Oncology Research, Houston.

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