High-dose Chemotherapy Improves Breast Cancer Survival (dateline October 13, 1999)

 A recent study led by Dr. David A. Rizzieri of Duke University Medical Center revealed that the early use of high-dose chemotherapy and other aggressive treatment of metastatic breast cancer may significantly improve a patient’s outcome, compared to standard-dose chemotherapy.

The study, conducted between 1987-1995, tracked 425 women with metastatic breast cancer (cancer that has spread to distant parts of the body) who had been previously treated with standard-dose chemotherapy. 113 of the women enrolled in the study went into complete remission after treatment while 202 had a partial response to the treatment. Dr. Rizzieri’s group then took the patients who had completely responded to the chemotherapy and randomly assigned them into two groups: one group would receive high-dose chemotherapy (or other aggressive treatments) while the other group would not receive any treatment until breast cancer symptoms reappeared. In addition, all of the women who had partial responses to standard-dose chemotherapy were given high-dose chemotherapy.

Of the 425 metastatic breast cancer patients who entered the trial, 11% remain disease free after five years. Of all the patients who received a regimen of standard chemotherapy followed immediately by high dose therapy and autologous stem cell support, 16% remain disease free after five years. Autologous stem cell rescue involves the use of the patient's own blood to obtain stem cells, the precursors of all blood cells. Stem cells will regenerate bone marrow function in the patient after high-dose chemotherapy. "If a patient attains a complete response by the end of the whole therapy, there is a 28% chance of remaining free of disease through five years," Dr. Rizzieri told Imaginis.net.

Early aggressive treatment may result in increased treatment success

In contrast to the customary method of offering standard chemotherapy and then waiting to see if symptoms of further cancer involvement develop, Dr. Rizzieri and his colleagues believe that aggressively treating early metastases, when the disease is minimal, results in significantly better prognoses for patients.

"We feel that those who are candidates for, and interested in an aggressive approach to their care if metastatic disease is found should be followed closely to find the metastatic disease before it is more advanced and more difficult to get to remission," said Dr. Rizzieri.

Dr. Rizzieri noted specific factors that predict a better chance of longer remission with high-dose chemotherapy:

• a long period of time between initial diagnosis of breast cancer to the diagnosis of metastases, indicating a slower rate of cancer spreading
• prior use of the breast cancer treatment drug tamoxifen
• hormone receptors positivity (respond well when stimulated)
• smaller size of metastatic cancers
• metastases limited to the chest wall/nodes as opposed to the visceral organs (the internal organs, mainly stomach and intestines)

The Duke study could lead to significant advancements in the way breast cancer patients with metastases are treated. "We feel that [an aggressive approach] leads to a remission or at least to a position of a minimum amount of residual disease for the patient. [At this point] we can use this as a springboard for combining it with future improvements in alternative therapies including tumor vaccines and an anti-angiogenesis approach which our group is now focusing on." Angiogenesis is the ability to grow blood vessels; a common feature of cancerous tissue Click here for more information on angiogenesis and a new drug, angiostatin, being developed to treat cancer.

Recovery, reduction of side effects

Dr. Rizzieri’s study required approximately three weeks of recovery for patients at the Duke outpatient transplant center, followed by several weeks of recovery at home to improve nutrition, endurance, and strength after exposure to high-dose chemotherapy. The side effects of chemotherapy typically included increased risk of infections and severe lung scarring. "Recognition of these risks has led to a significant decrease in severe side effects from this procedure today, as compared to when the study was begun ten years ago," noted Dr. Rizzieri.

Though the study does not specifically address patients with early stages of breast cancer such as ductal carcinoma in situ (DCIS), the collected data has led to trials with women with earlier stage breast cancer and multiple axillary lymph nodes. "Those [women] with early stage disease should be counseled that there are multiple ongoing trials with standard therapies as well as high-dose therapy for their disease," said Dr. Rizzieri. "They should make the choice that best fits their desires for degree of risk/aggressiveness of care and potential benefits based on preliminary data."

References and additional resources:

• Information in this article was obtained through an interview Imaginis.net conducted with Dr. Rizzieri on October 12, 1999.
• This article also references the October 1, 1999 Reuters Health report, "Early Chemotherapy Improves Breast Cancer Survival" available at http://www.reutershealth.com.
• Dr. Rizzieri and colleagues have published a medical report on the findings of their study in the October 1999 issue of the Journal of Clinical Oncology and can be found at: http://www.jco.org/cgi/content/full/17/10/3064?maxtoshow=&HITS=&hits= &
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  Breast+Cancer
• The Duke University Medical Center press release by Joanna Downer is available at: http://news.mc.duke.edu/infomatters/News/News.taf?_f=detail&key=2645&site=
  DUMCNEWS&_UserReference=0D72DC61EA177D56BBAEECB0