Study hints of way around breast cancer drug's drawbacks

SAN ANTONIO -- The drug Herceptin, already viewed as promising for women with both early and late-stage breast cancer, got another boost yesterday with new research showing that the heart damage it sometimes causes might be avoidable.

It also might still be effective when given for a shorter time, a finding that could drastically lower the cost of the pricey treatment.

At a meeting of more than 7,000 breast cancer specialists yesterday, Finnish doctors said nine weeks of Herceptin instead of the usual year prevented recurrences and did not raise the risk of heart failure. A second study found that pairing it with novel chemotherapy gave good results and avoided much of the risk of heart damage.

The findings make a convincing case for using Herceptin earlier in breast cancer treatment, said Dr. Robert Carlson, a Stanford University breast cancer expert who had no role in the studies.

''The jury is in and the jury has a very strong verdict" -- that virtually all women whose tumors are the type targeted by Herceptin should get the drug, he said.

Herceptin works against a gene that is overactive in about one-fourth of breast cancers. About 50,000 women in the United States and 250,000 worldwide are diagnosed with this type each year. Herceptin targets cancer cells, avoiding the side effects of most other treatments.

It was approved in 1998 for advanced breast cancer, but its maker, Genentech, wants to sell it for women with early-stage disease, which is when most women are diagnosed. Recent studies on such women found it cuts the risk of recurrence and one analysis suggests it improves survival.

But it can also raise the risk of heart failure, especially in women also taking older chemotherapy drugs called anthracyclines.

Dr. Dennis Slamon, a scientist at UCLA's Jonsson Cancer Center who led Herceptin's development, tested its effectiveness in 3,222 women around the world on various chemotherapy drugs.

Women got one of three regimens: standard treatment with Adriamycin (an anthracycline) and carboplatin followed by Taxotere; standard treatment plus a year of Herceptin; or a novel combination, Taxotere and carboplatin plus Herceptin but no anthracycline.

Two years later, 147 of the women on standard treatment had died or relapsed compared with 77 and 98 women in the two groups, respectively, that got Herceptin. The difference between the Herceptin groups was not statistically significant, suggesting the benefits could be obtained without the risk of the anthracycline.

Information on heart damage supported this claim. Heart failure severe enough to cause symptoms like breathing problems was rare but was more common in the Herceptin groups than those on standard chemotherapy alone.

However, a larger proportion had less severe heart damage, and it was least common among those who skipped the anthracycline.

''Herceptin is very safe" except when taken with an anthracycline, Slamon said.

The study was funded by Sanofi-Aventis, makers of Taxotere, and Genentech. Slamon has been a paid speaker for both.

Further analysis of the women's tumors turned up evidence that two-thirds were not likely to benefit from anthracyclines anyway, Slamon said.

Several experts said they weren't ready to abandon this mainstay of cancer treatment. ''They work," said Dr. Larry Norton, breast cancer chief at Memorial Sloan-Kettering Cancer Center in New York.