December 8, 2005

Chemo regimen can limit Herceptin heart risk-study

LOS ANGELES (Reuters) - The breast cancer drug Herceptin,
shown recently to improve survival in women with early-stage
breast cancer, carries with it a risk of heart damage, but a
chemotherapy regimen can limit the danger, researchers said on

Genentech Inc.'s Herceptin has been on the market since
1998 as a treatment for the 25 percent to 30 percent of breast
cancer patients, who have tumors that generate a protein called
HER-2 and whose cancer has spread beyond the breast.

These tumors tend to grow faster and are more likely to
recur than tumors that do not carry the protein.

Herceptin, given by injection, is an antibody-based drug
designed to target tumor cells and spare normal cells, unlike
chemotherapy which is toxic throughout the body.

Since the announcement earlier this year of positive trial
results for Herceptin in combination with chemotherapy in
earlier-stage cancer, physicians have begun to use the drug in
these patients.

Genentech has said it plans to file in the first quarter of
2006 for regulatory approval of Herceptin in early-stage breast
cancer after surgery.

A study conducted by the Breast Cancer International
Research Group, early results of which were announced in
September, found that Herceptin plus standard chemotherapy
reduced the risk of disease recurrence in early breast cancer
by 51 percent.

"The chemotherapy combinations we tested with Herceptin
proved to be superior to the best available standard therapy
for early breast cancer," Dr. Dennis Slamon, the study's
principal investigator and director of clinical/translational
research at UCLA's Jonsson Cancer Center, said in a statement.

He presented the full study results at the San Antonio
Breast Cancer Symposium.

The 3,222 women enrolled in the trial received either
standard treatment with Adriamycin and Carboplatin followed by
Taxotere, an experimental regimen of Adriamycin and Carboplatin
followed by Taxotere and one year of Herceptin or Taxotere and
Carboplatin with one year of Herceptin.

Slamon said researchers knew that giving Herceptin with
Adriamycin resulted in heart damage in some patients, the most
severe of which was congestive heart failure. The study showed
that the cardiac toxicity was significant and continued past
the study's 18-month follow-up.

The trial found that 306 patients lost more than 10 percent
of heart function. Of those, 91 received standard chemotherapy;
82 were in the arm that excluded Adriamycin; and 180 were in
the arm which paired Adriamycin with Herceptin.

The good news, Slamon said, is that Herceptin given with
the chemotherapy combination that eliminated Adriamycin is
still significantly superior to the best available chemotherapy
alone, reducing risk of relapse by 39 percent.

The study's other important finding is that a subset of
HER-2 positive patients -- about 35 percent -- also have
amplification of a gene called topo II, which makes them more
likely to respond to Adriamycin. As Herceptin targets HER-2,
Adriamycin targets topo II.

Patients who test positive for amplification of both HER-2
and topo II might opt for the drug regimen with Adriamycin,
risking heart damage in exchange for a better response to
therapy, Slamon said.

He said a test that indicates both HER-2 and topo II
amplification is being developed so doctors will better be able
to tell which patients should be on which drug regimen.

"Women will have the information they need to decide if the
risk is worth the benefit," Slamon said.