Low-dose chemotherapy plus antiangiogenesis drug has activity in advanced breast cancer

December 08, 2005

Chemotherapy given in low, frequent doses - a novel strategy called "metronomic" delivery - achieved partial shrinkage of disease in some advanced breast cancer patients when given concurrently with an angiogenesis inhibitor, report researchers from Dana-Farber Cancer Institute in Boston.

In a pilot study of 55 patients, the combination of low-dose chemotherapy and the anti-VEGF antibody, bevacizumab (Avastin; Genentech) delayed the breast cancer's progression by an average of 5 ½ months, compared to two months with the low-dose chemotherapy alone, said Harold Burstein, MD, PhD, a medical oncologist at Dana-Farber. He will present the results in a General Session at the annual San Antonio Breast Cancer Symposium on Thursday, Dec. 8.

"Pairing metronomic therapy with a dedicated angiogenesis inhibitor showed clinical activity, and was quite well tolerated," said Burstein. "We think this is a combination worth pursuing and are exploring this treatment concept further in a Phase II study, which extends these treatments into early stage breast cancer therapy."

The current study is one of the first rigorous tests of a treatment strategy that was proposed several years ago as a means of improving the results of chemotherapy for breast cancer, said Burstein, who is also an assistant professor of medicine at Harvard Medical School.

Historically, high doses of chemotherapy are given at intervals of two to three weeks, with time off the drug to recover from side effects. However, laboratory researchers have suggested that this rest period also allows the blood vessels feeding the tumor to re-form after they had been destroyed by the chemotherapy. They proposed giving smaller, almost constant doses of the drug - as regular as the ticking of a metronome - as a way to hamper angiogenesis (the growth of new blood vessels).

In the Dana-Farber study, the chemotherapy drugs cyclophosphamide and methotrexate were given in a metronomic regimen to 21 patients with advanced, metastatic breast cancer. In another 34 patients, the chemotherapy was paired with the angiogenesis inhibitor bevacizumab, or Avastin, given intravenously every 14 days. None of the patients had been previously heavily treated for their advanced cancer.

The metronomic-alone therapy led to two partial responses (10 percent of the patients), while in another eight patients the cancer remained stable. Results seemed better in the combination group, in which 10 patients (29 percent) had partial responses, while 14 (41 percent) experienced stable disease. There were still some side effects in both groups, including fatigue, but Burstein said the therapies were generally well tolerated and lacked the major side effects of traditional chemotherapy such as gastrointestinal and hair loss.

The researchers concluded that the metronomic therapy by itself had limited clinical activity, but the activity seen when the antiangiogenesis drug was added suggests "further investigation of this novel treatment study is warranted."
Support for the trial came from a National Cancer Institute-Avon Partners for Progress Award, a breast cancer SPORE (Specialized Program of Research Excellence) grant to the Dana-Farber/Harvard Cancer Center, and from Genentech, Inc., manufacturer of Avastin.

Dana-Farber Cancer Institute (www.dana-farber.org) is a principal teaching affiliate of the Harvard Medical School, and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive care center the National Cancer Institute.

Dana-Farber Cancer Institute

Related Breast Cancer Articles from Brightsurf:

Oncotarget: IGF2 expression in breast cancer tumors and in breast cancer cells
The Oncotarget authors propose that methylation of DVDMR represents a novel epigenetic biomarker that determines the levels of IGF2 protein expression in breast cancer.

Breast cancer: AI predicts which pre-malignant breast lesions will progress to advanced cancer
New research at Case Western Reserve University in Cleveland, Ohio, could help better determine which patients diagnosed with the pre-malignant breast cancer commonly as stage 0 are likely to progress to invasive breast cancer and therefore might benefit from additional therapy over and above surgery alone.

Partial breast irradiation effective treatment option for low-risk breast cancer
Partial breast irradiation produces similar long-term survival rates and risk for recurrence compared with whole breast irradiation for many women with low-risk, early stage breast cancer, according to new clinical data from a national clinical trial involving researchers from The Ohio State University Comprehensive Cancer Center - Arthur G.

Breast screening linked to 60 per cent lower risk of breast cancer death in first 10 years
Women who take part in breast screening have a significantly greater benefit from treatments than those who are not screened, according to a study of more than 50,000 women.

More clues revealed in link between normal breast changes and invasive breast cancer
A research team, led by investigators from Georgetown Lombardi Comprehensive Cancer Center, details how a natural and dramatic process -- changes in mammary glands to accommodate breastfeeding -- uses a molecular process believed to contribute to survival of pre-malignant breast cells.

Breast tissue tumor suppressor PTEN: A potential Achilles heel for breast cancer cells
A highly collaborative team of researchers at the Medical University of South Carolina and Ohio State University report in Nature Communications that they have identified a novel pathway for connective tissue PTEN in breast cancer cell response to radiotherapy.

Computers equal radiologists in assessing breast density and associated breast cancer risk
Automated breast-density evaluation was just as accurate in predicting women's risk of breast cancer, found and not found by mammography, as subjective evaluation done by radiologists, in a study led by researchers at UC San Francisco and Mayo Clinic.

Blood test can effectively rule out breast cancer, regardless of breast density
A new study published in PLOS ONE demonstrates that Videssa® Breast, a multi-protein biomarker blood test for breast cancer, is unaffected by breast density and can reliably rule out breast cancer in women with both dense and non-dense breast tissue.

Study shows influence of surgeons on likelihood of removal of healthy breast after breast cancer dia
Attending surgeons can have a strong influence on whether a patient undergoes contralateral prophylactic mastectomy after a diagnosis of breast cancer, according to a study published by JAMA Surgery.

Young breast cancer patients undergoing breast conserving surgery see improved prognosis
A new analysis indicates that breast cancer prognoses have improved over time in young women treated with breast conserving surgery.

Read More: Breast Cancer News and Breast Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.