Studies show little advantage to high-dose chemotherapy for high-risk breast cancer

An aggressive and grueling treatment for breast cancer that uses doses of chemotherapy so high that it destroys the patient's bone marrow offers little or no benefit over standard chemo for women who

Thursday, July 3rd 2003, 12:00 am

By: News On 6

An aggressive and grueling treatment for breast cancer that uses doses of chemotherapy so high that it destroys the patient's bone marrow offers little or no benefit over standard chemo for women who run the risk of a recurrence, two studies show.

The research could signal the end for the expensive and controversial treatment, though some believe it may eventually prove superior in some women.

Ultrahigh-dose chemotherapy employs many times the normal level of cancer drugs. Because the treatment also kills the bone marrow, the patient has to get a transplant of blood-forming stem cells collected from her own body.

The approach became widely used for advanced breast cancer when preliminary studies suggested it was better than the conventional chemotherapy offered to women after surgery.

But more rigorous studies in the 1990s found that the intensive treatment did not improve the outcome for women whose cancer had spread to other parts of the body. Because of those disappointing results, the approach is seldom used now outside of medical studies.

The research in Thursday's New England Journal of Medicine looked at the treatment in patients whose cancer had spread only to their lymph nodes, putting them at high risk for a relapse.

In both studies, there was little difference between the two approaches in survival after five or six years or in the rate of cancer recurrence.

``I think the evidence of benefit is so minimal ... and the toxicity is so substantial and the cost so high that by and large people are going to say this approach is now no longer worthy of pursuing in any major way,'' said Dr. Harmon Eyre, chief medical officer of the American Cancer Society.

The high-dose regimen costs at least $150,000, while standard chemo is $8,000 to $10,000, according to Eyre. He said the future of breast cancer treatment may be drugs designed to kill only cancer cells and not healthy cells and regimens tailored for each patient.

Insurance companies initially balked when women desperate for a cure demanded they pay for the intensive but unproven treatment. But many later relented under pressure from lawsuits and state laws mandating coverage.

Dr. Martin S. Tallman of Northwestern University Feinberg School of Medicine, who led one of the studies, said the results could make it difficult to pursue the high-dose technique.

``It will be hard to generate enthusiasm and resources when, in general, the results have been disappointing ... and there are other alternatives people are enthusiastic about,'' he said.

But another researcher, Dr. Sjoerd Rodenhuis, said he is not giving up on high-dose treatment. His study, done in the Netherlands, suggests the treatment may work better in the three-quarters of patients whose tumors test negative for a defect in a certain gene. The gene, called HER2-neu, plays a role in regulating cell growth; excess copies of the gene cause cells to reproduce out of control.

Patients without the defect seemed to respond better to the high-dose treatment, but Rodenhuis said that needs to be independently confirmed.

``We believe that high-dose chemotherapy is going to be back _ but obviously not for all patients,'' said Rodenhuis of the Netherlands Cancer Institute.

In an accompanying editorial, Dr. Gerald J. Elfenbein of Roger Williams Medical Center in Providence, R.I., said there may be other groups of women who could benefit from high-risk chemotherapy, noting that neither study looked at race or ethnic groups.

The Dutch study involved 885 women with four or more cancerous lymph nodes, while the 511 women in the U.S. study had 10 or more. Some of the Dutch patients received five cycles of standard chemotherapy; others got four standard cycles, plus one cycle of high-dose chemo and a stem cell transplant. The U.S. women all got six cycles of standard chemo; those in the high-dose group then received high-dose chemo and a transplant.

While there was no survival difference overall, when the Dutch researchers looked only at the patients with 10 or more cancerous nodes, they found a slightly better relapse-free survival rate for those in the high-dose group, 61 percent, compared with standard chemo, 51 percent.

Five deaths in the Dutch study were caused by the high-dose treatment and nine in the U.S. study were transplant-related, mostly from bone marrow transplants early in the study. Side effects included nausea, vomiting, mouth sores and infection.

Tallman said it was initially difficult to get patients to take part in the U.S. study when it started in 1991 because of the belief that high-dose chemo worked better. But the latest findings illustrate how important it is to do controlled studies to prove whether promising-looking approaches really do work.