WebMD Medical News
Laura J. Martin, MD
Aug. 22, 2011 -- An experimental drug that has been shown to be effective in treating ovarian cancer in patients with BRCA1 or BRCA2 gene mutations also appears to work in some patients without the mutations.
The drug olaparib is one of several experimental treatments that block the activity of the protein PARP, which, like BRCA, is involved in DNA repair.
In earlier trials, PARP inhibitors have been shown to promote tumor cell death in breast and ovarian cancer patients with BRCA mutations by preventing the cells from repairing their DNA.
But the new study is the first to suggest the drugs may prove effective in a broader group of patients with non-inherited cancers who have few treatment options, lead researcher Karen Gelmon, MD, of Vancouver, Canada’s BC Cancer Agency tells WebMD.
The study included 65 ovarian cancer patients and 26 breast cancer patients with highly aggressive, advanced forms of the diseases.
Prior to entering the study, the patients had been treated with an average of three different chemotherapy regimens, and some had received as many as 10 different treatments.
Some of the patients carried the BRCA1 or BRCA2 mutations while others did not.
All of the patients were treated with 400 milligrams of olaparib twice a day for a month between July 2008 and September 2009. Side effects were described as well tolerated and included fatigue, nausea, vomiting, and decreased appetite.
Ovarian cancer patients who took part in the trial had high-grade serous tumors, which share similar traits to tumors in women with BRCA mutations.
After taking the experimental drug for four weeks, 41% of the ovarian cancer patients with BRCA mutations and 24% of those without a mutation showed substantial shrinkage in the size of their tumors.
Responses were not seen in breast cancer patients with triple-negative tumors -- tumors that do not respond to hormonal treatments or those targeting HER2 receptors.
While the response in these breast cancer patients was disappointing, the response in the ovarian cancer patients suggests that the drug may have a role in the treatment of patients without BRCA mutations, oncologist Melinda Telli, MD, tells WebMD.
Telli is an assistant professor of medicine in the division of medical oncology at Stanford University in Stanford, Calif.
“We thought this class of drugs might have a larger role to play, and this is the first study to confirm that this might be the case,” she says.
The study was published online and will appear in the September issue of The Lancet Oncology. Drug manufacturer AstraZeneca, which hopes to market the drug pending FDA approval, funded the research.
Earlier this year, another PARP inhibitor, Sanofi-Aventis’ iniparib, failed to extend overall survival in a study involving women with advanced, triple-negative breast cancer when added to a standard chemotherapy regimen.
Telli says PARP inhibitors may still prove useful for the treatment of this type of highly aggressive, hard-to-treat cancer.
“There is a lot more to this story and a lot more research to be done,” she says.
SOURCES:Gelmon, K.A. The Lancet, Sept. 2, 2011; vol 12: pp 852-861.Karen A. Gelmon, MD, professor of medicine, BC Cancer Agency, Vancouver, Canada.Melinda Telli, MD, assistant professor of medicine, division of medical oncology, Stanford University Medical Center, Stanford, Calif.News release, The Lancet.O’Shaughnessy, J. Journal of Clinical Oncology, 2007.
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