Breast Cancer Drug Won't Work Against Lung Cancer

Study dashes hopes for another use for Herceptin

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By
HealthDay Reporter

TUESDAY, Jan. 13, 2004 (HealthDayNews) -- A drug that has been extraordinarily effective in the fight against breast cancer has failed to live up to expectations that it might do the same for lung cancer patients, a German study has found.

Patients suffering from non-small-cell lung cancers (NSCLC) who were treated with the drug Herceptin (trastuzumab), in combination with chemotherapy, did no better than patients treated with chemotherapy alone.

The findings, which appear in the January issue of the Annals of Oncology, have diminished hopes that the drug could have as dramatic an impact on extending the lives of lung cancer patients as it has for women with breast cancer.

Herceptin, which is marketed by the American biotech firm Genentech Corp. and F. Hoffmann-La Roche of Switzerland -- the companies that funded the study -- targets cancer cells that make too much of a protein called HER-2, which is found on the surface of cancer cells.

"We don't exactly know the underlying mechanisms why," says lead researcher Dr. Ulrich Gatzemeier, head of thoracic oncology at Grosshansdorf Hospital in Germany. "But we have not seen that Herceptin adds anything significant to the chemotherapy" for this specific group of patients.

The amount of HER-2 protein in cancer tumors is measured using a scale from 0 (negative) to 3+ (strongly positive); patients with a negative over-expression were excluded from study. The main reason for the failure to show results in lung cancer, Gatzemeier says, was the majority of patients had lower levels (1+ and 2+) of high HER2 over-expression.

He added it was also possible that blocking only one of the growth factors was not effective since there were parallel signaling pathways allowing the cancer to progress.

Researchers had believed that since previous studies on HER-2 positive NSC lung cancers had shown that Herceptin had an even greater synergy with the chemotherapy agents gemcitabine and cisplatin than it had in breast cancer cells, there was reason to believe that it might also benefit lung cancer patients.

"Because of some of these synergies we have seen in past experiments, we felt there was a rationale to try it on lung cancer patients. But, as we have seen, we have not found this has proven to be the case," Gatzemeier adds.

Herceptin, which was approved by the U.S. Food and Drug Administration in 1998, works by inactivating HER-2, which is found in 25 percent to 30 percent of all breast cancers and makes cancer cells grow especially rapidly. It has been credited with slowing, or even stopping, the progression of the disease and significantly extending the lives of breast cancer patients.

There were hints in the results of the study that there could be a very small subgroup of lung cancer patients who may benefit from Herceptin; those were patients with extremely strong over-expression (3+) of the gene HER2, which the drug targets.

"Yes, the results are a failure," Gatzemeier adds. "But from a scientific point of view, we believe that there is a little bit of hope for the 3+ segment" of the patients.

About 80 percent of lung cancers are NSC, and it's one of the leading causes of cancer deaths.

"Before there wasn't really a lot of data on the expression of HER-2 in lung cancer," says Alexander Klauser, a spokesman for F. Hoffmann La Roche. "We have known about this data for some time, now, and it has been presented at several congresses already, so it's nothing new for us. And it has no impact on our business."

"This was a small trial, but for us it's not worthwhile to really pursue more trials at this time," he adds.

More information

Learn more about non-small-cell lung cancer from the University of Maryland or the American Cancer Society.

SOURCES: Ulrich Gatzemeier, M.D., head, Department of Thoracic Oncology, Center for Pneumology and Thoracic Surgery, Grosshansdorf Hospital, Grosshansdorf, Germany; Alexander Klauser, media relations spokesman, F. Hoffmann-La Roche AG, Basel, Switzerland; January 2004 Annals of Oncology

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