High-dose chemotherapy has only a minimal effect on survival in breast cancer patients with node-positive disease, new research shows.

“It’s pretty clearly established that [high-dose chemotherapy] is a false hope,” said study author Donald Berry, head of the Division of Quantitative Sciences at the University of Texas M.D. Anderson Cancer Center in Houston. “There’s a disease-free survival benefit but not much of a survival benefit. There may be a subset which would benefit, but we looked and couldn’t find it.”

The study, done in collaboration with the European Blood and Marrow Transplant Group, essentially sounds the death knell for this type of therapy.

“When you’re doing a meta-analysis and combining large numbers of studies with different populations, and you’re not able to get a really significant survival advantage, I think that the benefits of high-dose chemo are not there,” added Dr. Jay Brooks, chairman of hematology/oncology at Ochsner Health System in Baton Rouge, La. “Outside of a clinical research trial, I do not recommend high-dose chemotherapy.”

The findings are expected to be presented Thursday at the San Antonio Breast Cancer Symposium.

High-dose chemotherapy for breast cancer has a somewhat controversial history. The treatment is delivered in conjunction with an autologous (from the same person) bone marrow transplant, which rebuilds bone marrow damaged by the chemotherapy. The regimen was at one time favored for high-risk patients (those whose cancer has spread to at least four lymph nodes).

The rationale for the treatment came from successes in the 1960s and 1970s in treating certain leukemia patients with radiation and high-dose chemotherapy, along with bone marrow transplants.

By the late 1980s, the regimen was all the rage. An estimated 20,000 to 30,000 U.S. women have undergone high-dose chemotherapy with bone marrow transplants.

“Ten years ago, if a woman didn’t get a bone marrow transplant, people were suing HMOS, because they said they were denying care,” Brooks said. “The cases won.”

Although progressively easier to tolerate, the therapy often caused nausea, vomiting, extreme weakness and infection. Some patients even died from the treatment.

Some small studies found that the treatment was beneficial for women with very high-risk cancer (at least 10 positive lymph nodes), but the trials were not randomized.

Later, randomized trials did not confirm the same benefit, and the treatment has largely fallen out of favor.

“But there were still some nagging questions,” Berry said. “One was that maybe there was a subset who benefited.”

Berry and his colleagues reviewed 15 randomized studies of high-dose chemotherapy conducted around the world between 1988 and 2002. Together, the trials involved more than 6,000 patients with a median follow-up of seven years.

There was a 13 percent decrease in the rate of breast cancer relapse in patients receiving high-dose chemotherapy. But that benefit did not extend survival. The decrease in mortality was only 6 percent, which was not statistically significant.

Increasing doses of chemotherapy do have some benefit for breast cancer patients, but it does reach a point of diminishing returns.

“Increasing the dose is good, but it reaches a plateau,” confirmed Berry.

(Source: NHIC)