A new drug cocktail might be the right mix to fight breast cancer after it becomes resistant to standard therapy. Details of a new study supporting this approach suggest it's possible to re-sensitize tumors thus allowing treatments to work again. The findings were presented December 11 at the CTRC-AACR San Antonio Breast Cancer Symposium.
The study involves post-menopausal women whose advanced breast cancers are fueled by estrogen, often called estrogen-receptor or progesterone-receptor positive cancers. The standard treatment is anti-hormonal medicines, such as aromatase inhibitors (AIs), which lower the amount of estrogen in the body. Over time, however, the cancer figures out a way to thrive without the estrogen. The treatment strategy under investigation to fight this resistance combines an aromatase inhibitor with sorafenib, an oral medication FDA-approved to treat liver and kidney cancers.
"We believe the sorafenib might disrupt the machinery created by the tumor to grow without the estrogen," says Claudine Isaacs, MD, clinical director of breast cancer program at Georgetown Lombardi Comprehensive Cancer Center and presenting author of the study. "After the machinery is destroyed, the aromotase inhibitor can do its work again. We're already seeing some encouraging responses to this approach."
The multi-center, phase II study involves 35 post-menopausal women with metastatic breast cancer resistant to aromotase inhibitors. The women continue taking an aromotase inhibitor for the study, but they also take sorafenib. The analysis presented at the symposium demonstrates a clinical benefit rate in 20 percent of the women. Clinical benefit means the patient has a complete or partial response and includes those who have stable disease for at least 6 months (24 weeks).
Isaacs says this finding suggests that sorafenib is acting to reverse resistance to AIs as this type of response would not have been expected with either sorafenib alone or with continuing the AI.
"To manage breast cancer long term, it's apparent that we may need to continually switch drugs to keep up with how a cancer evolves and evades each approach," Isaacs concludes.
Isaacs says side-effects were common but most were mild or were managed by reducing the dose. Such side effects included redness and irritation of the palms and soles, skin rash, fatigue, nausea/vomiting and diarrhea. Serious hypertension occurred in about 11 percent of the patients. Isaacs says this factor was more easily managed if blood pressure was brought under good control before patients were administered the combination.
This study was funded by the Avon Patient for Progress Award and supported in part by Bayer. Isaacs is part of a speaker's bureau for Pfizer, the maker of Exemestane, an aromatase inhibitor. She is also on speaker's bureau for Abraxis Oncology, Genentech, GlaxoSmithKline, and Novartis.
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