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From Medscape Medical News > Oncology

Controversial Therapy May Benefit Advanced Breast Cancer

Fran Lowry

July 28, 2011 — Better-than-expected survival in patients with stage IV breast cancer who were treated with high-dose chemotherapy (HDCT) and purified blood stem cells more than a decade ago is prompting a new look at the controversial treatment.
An update on the long-term outcomes of women with advanced breast cancer who were treated aggressively with HDCT followed by rescue with their own blood stem cells, which had been purged of cancer, was published online July 18 in Biology of Blood and Marrow Transplantation.
"This is a controversial treatment," senior author Judith A. Shizuru, MD, PhD, from Stanford University in California, told Medscape Medical News.

Dr. Judith Shizuru

[The original article has her picutre inserted here. You can get a free log-in from Medscape to view it - use Rich's link http://www.medscape.com/viewarticle/747179 in his posting .]

"A number of studies in the 1990s suggested that this treatment would be effective for women with advanced breast cancer, but then other randomized trials showed no particular benefit," she said.
There has also been controversy. Werner Bezwoda, MD, from the University of Witwatersrand, Johannesburg, South Africa, reported positive results with HDCT and autologous stem cell rescue at the 1999 annual meeting of the American Society Clinical Oncology, but when it emerged that he had falsified his results, the ensuing uproar helped put the kibosh on further studies of this aggressive and expensive treatment.
"Most people in the oncology community now feel that this is a done deal and that this aggressive treatment does not work," Dr. Shizuru said. "I think we should be taking another look."
In their report, Dr. Shizuru and lead author Antonia M.S. Muller, MD, also from Stanford, looked at the long-term outcome of a pilot study of 22 patients with metastatic breast cancer enrolled from December 1996 to February 1998.
The patients were treated at Stanford or at the Barbara Ann Karmanos Cancer Institute in Detroit, Michigan.
The small phase 1/2 study was undertaken to test the effectiveness and feasibility of using highly purified stem cells from circulating blood, instead of an unmanipulated blood graft, for transplantation.
"We knew that you could have micrometastases in the bone marrow, so it was likely that you could mobilize cancer cells into the blood stream when you gave a blood stem cell transplant," Dr. Shizuru explained. "We purified the stem cells to make sure that there was no cancer contamination."
They found that more than 12 years after the end of the study, 5 of the 22 patients had survived. In addition, 4 of these patients were free from recurrence and had normal hematopoietic function.
The study also showed that the median progressive-free survival of these patients with advanced breast cancer was 16 months, and that median overall survival was 60 months.
In contrast, a retrospective comparison of 74 patients transplanted between 1995 and 1999 with the identical high-dose chemotherapy regimen, but who received unmanipulated blood stem cells, showed that only 7 (9%) of the patients are alive; of these, 7% are without disease.
In this historic cohort, median progressive-free survival was 10 months and median overall survival was 28 months.
"This is quite a difference, even though this is a small sample," Dr. Shizuru said.
"We weren't really planning to open up the whole field again, but I think — from looking at how these surviving women have done — ...[it's] good to know that we can give them back a pure blood stem cell product that's been fairly well processed and they can still make blood cells normally after so many years," Dr. Shizuru noted.
She cautioned that the pilot study is small. "Usually, you would want to have many more patients before you jump to any major conclusions, but we feel that, with this second look, the findings are very striking to us, and we want to rethink and reexamine this treatment," she said. "We are definitely going to try to study this further."
Logistics of Doing So Will Be Formidable
Max Wicha, MD, professor of medicine at the University of Michigan Comprehensive Cancer Center in Ann Arbor, is skeptical that further studies of this therapy will end up being done.
"Is it actually worth doing a large randomized study, which is what it would take to prove one way or another whether this aggressive treatment really works? Such a trial is very expensive and involves a lot of potential toxicity," he said when approached for comment.
"I don't think you could recruit the women, given the state of this field and how most people are so against it. I doubt that you could get women to agree to become part of such a study because there has been so much publicity about how it really doesn't work," he said.
In Dr. Wicha's opinion, the most interesting aspect of this small study is the revelation that using purified blood stem cells does not interfere with a patient's ability to reconstitute normal blood elements in the long term.
However, this does not prove that using stem cells improves survival, he said.
"My belief is quite strong that the reason this treatment regimen doesn't work and that patients relapse is because the actual cancer stem cells are resistant, even to high doses of chemotherapy, so you never really get rid of them once you have metastatic disease. The cancer just comes back. What we really need are cancer stem cell targeted therapies, not just more chemotherapy and bone marrow transplant," he said.
Dr. Shizura and Dr. Wicha have reported no relevant financial relationships.
Biol Blood Marrow Transplant. Published online July 18, 2011. Abstract