Ovarian Cancer Study Proves Drug Delays Disease Progression, May Improve Survival
Main Category: Ovarian CancerArticle Date: 29 Dec 2011 - 1:00 PST
Treating ovarian cancer with the drug bevacizumab ("Avastin") delays the disease and may also improve survival, show the results of an international clinical trial co-led by Drs. Amit Oza of the Princess Margaret Cancer Program, University Health Network and Timothy Perren, St James's Institute of Oncology, Leeds, UK.
The findings, published today in the New England Journal of Medicine, report that the drug halted the cancer's return for two months overall. However, for women with the highest risk disease, the delay was five to six months and in this group, the findings also indicate a strong trend to improved overall survival, which is being analysed until 2013.
"This is the first new drug in ovarian cancer in 15 years to improve outcome and I believe it should be considered as a potential new standard of care," says Dr. Oza, a medical oncologist who leads the Cancer Clinical Research Unit at Princess Margaret Hospital. He is also co-director of the hospital's Bras Family Drug Development Program and Professor, Faculty of Medicine, University of Toronto.
The seven-year study began in 2004 and enrolled 1,528 women with ovarian cancer at 263 centres, including 20 in Canada. Avastin was added to chemotherapy treatment and given intravenously every three weeks for 12 months.
The drug blocks growth factors that promote new blood vessels formation in tumours, thereby "starving" the cancer. It is not a cure, explains Dr. Oza, but has a proven track record in delaying disease progression in other types of cancer including colorectal, lung, breast, kidney and brain.
"We now know that using Avastin in ovarian cancer for even this short time improves outcomes," says Dr. Oza. "The next step is to determine if giving it for a longer period would be of even greater benefit."
Similar findings from a U.S. study are also reported in this issue of the journal. Dr. Oza says the major difference between the two studies is that the women in the American study were given twice as much Avastin. "So the question now is would half the dose for double the duration improve outcomes even more? This is an area to investigate further."
The Canadian Cancer Society estimates 2,600 new cases of ovarian cancer will be diagnosed this year and 1,750 women will die of the disease.
The research was funded and led by the Medical Research Council UK, with women from 11 countries participating in the study. The study was conducted in Canada by the NCIC Clinical Trials Group (NCIC CTG) at Queen's University in Kingston, Ontario in collaboration with the Medical Research Council UK. Dr. Oza's research is also supported by The Princess Margaret Hospital Foundation.
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With Low-dose Chemotherapy - You Wouldn't Need Avastin
posted by Gregory D. Pawelski on 30 Dec 2011 at 5:50 pmMany chemotherapy drugs, in addition to killing tumor cells, also fight angiogenesis. However, the anti-angiogenic effects of dose-dense therapy may be masked and marginalized by the way it is usually administered. The main targets of high-dose chemotherapy are presumed to be proliferating tumor cells. The main targets of low-dose chemotherapy are the endothelial cells of the growing vasculature of a tumor. In other words, chemotherapeutics are used as anti-angiogenic agents.
The process of angiogenesis is controlled by two distinct types of proteins, referred to as "angiogenic growth factors" and "angiogenesis inhibitors." Medical researchers have identified 19 angiogenic growth factors in the human body and 31 angiogenesis inhibitors. In a healthy body, a perfect balance of factors that promote and prevent angiogenesis is maintained. After cells become cancerous, the regulation of this balance is disturbed, stimulating the production of new blood vessels.
Targeted therapies, such as Avastin, were originally designed with the goal of replacing chemotherapy, to reduce the serious morbidities associated with standard high-dose chemotherapy. Although targeted therapies may be somewhat less toxic, most of them have been found to have very modest efficacy, at least when used as single agents in treating patients with advanced disease. They have therefore mainly been used in combination with standard chemotherapy or radiation protocols.
It is becoming more apparent to administer drugs to patients with certain types of cancer on a weekly schedule. The advantage of low-dose chemotherapy is the possibility of combining it with anti-angiogenic drugs as well as other types of targeted therapies, such as those that target specific signal-transduction molecules or with antitumor vaccines.
Blood vessel cells are less likely than tumor cells to become resistant to chemotherapy, so if cancer cells become drug resistant, these medicines should still be able to shrink tumors by destroying their blood supply. When administering both anti-tumor and anti-angiogenesis drugs, the endothelial cells (involved iin angiogenesis) are the first in the tumor to undergo cell death (apoptosis).
Adding Avastin, which only goes after VEGF-sensitive cancer cells, you need to go after other pro-angiogenic factors which can substitute for VEGF: FGF, PDGF, ephrin A1, angioprotein 1, IL-8, etc. And with Taxol promoting an increase of IL-8, how effective is it with Avastin? With the low-dose protocol having an anti-angiogenic effect, you really wouldn't need to add a drug like Avastin into the mix.
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