Sabtu, 01 Mei 2010

Combo May KO Triple-Negative Breast Cancer

WASHINGTON (MedPage Today) -- Researchers here say a combination of a taxane and the targeted biological agent bevacizumab might be effective against hard-to-treat triple negative breast cancer.

While many drugs target tumors that overexpress certain proteins, there are limited therapies for women who develop breast cancer that do not overexpress estrogen, progesterone, or HER2 genetics, according to Sophia Ran, PhD, professor of medical microbiology, immunology, and cell biology at Southern Illinois University School of Medicine in Springfield.

Ran and colleagues told attendees at the meeting of the American Association for Cancer Research that they tested the use of paclitaxel protein-bound particles for injectable suspension -- nab-paclitaxel (Abraxane) -- by itself or in combination with bevacizumab (Avastin).

She said that nab-paclitaxel could reduce tumor size, but the addition of bevacizumab had additive and synergistic impacts on the tumors in animal models of triple-negative breast cancer.

She said investigators injected laboratory mice with cancer cells (also laced with fluorescent and luciferase tags).

When these tumor-prone animals developed lesions 150 mm3 in size, researchers treated them with saline (control), bevacizumab 4mg/kg twice a week for 10 weeks, nab-paclitaxel 10mg/kg daily for five days, or with combination of nab-paclitaxel and bevacizumab.

Tumor growth rate was monitored using calipers. Metastasis was analyzed by measuring luciferase activity in the lymph nodes and lungs.

"This preliminary study demonstrated a high sensitivity to nab-paclitaxel plus bevacizumab," Ran told MedPage Today, "suggesting there may be a role for this combination therapy to significantly improve the health outcomes for patients with triple-negative breast cancer."

She said the combination therapy inhibited tumor growth by 100%. This result was highly significant compared with either control (P<0.001) or nab-paclitaxel (P=0.024) alone. "Importantly, only combination therapy reduced incidence of lymph node metastases 50% (P=0.007) and lung metastases by 87% (P=0.001). There were 10 animals in each of the treatment groups; half the mice in the combination group achieved complete tumor regression," she reported. Ran said that the tagging of the tumor cell lines may help make it easier to perform testing. "These tags allow for quantitative assessment of metastatic spread," Ran said. "This model can be used to study the biology of triple-negative breast cancer and for designing new approaches to treat this type of cancer." The combination is being investigated in clinical trials, she said. The study was funded by Abraxis. Ran disclosed financial relationships with Abraxis. Two of the co-authors on the paper are employees of Abraxis. Primary source: American Association for Cancer Research Source reference: Volk L, et al "Combination treatment of nab-paclitaxel and bevacizumab in a new model of triple-negative breast cancer" AARC 2010; Abstract 3852.












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