Unavailability of Avastin more dangerous risk for breast cancer patients, says FAMEDS

[News]

Breast cancer patients and their families will rally together on Tuesday, June 28, at 7:00 am outside of the Federal Drug Administration (FDA). At issue will be the FDA's final hearing to remove the anti-cancer drug Avastin from the approved medication list for treatment of late stage breast cancer, despite the FDA approving it in 2008 for use to treat breast cancer.

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[gdpawel]

Avastin combined with chemotherapy has improved the survival of some lung cancer patients. Avastin plus folfox has improved survival for some colon cancer patients. Avastin plus chemotherapy improves the survival of some breast cancer patients. The problem is that it doesn't improve the survival of all cancer patients.

Roche has reported that women with breast cancer who were treated with Avastin in combination with chemotherapy followed by the continued use of single-agent Avastin demonstrated a significant improvement in progression-free survival. It's unclear if Avastin can help increase the overall survival rate in this indication.

I remember a clinical oncologist involved with real-time studies under real-world conditions of drugs like Avastin, telling me when the FDA rules on the clinical utility of a drug, they use a broad-brush approach that looks at the global outcomes of all patients, determining whether these glacial trends reflect a true climate change.

The problem is that while Bethesda, Maryland may not be noticing significant changes in ocean levels, people who live on the Maldives are having a very different experience. As these scientists ponder the significance of Avastin, some cancer patients are missing out on a treatment that could quite possibly save their lives.

One breast cancer patient's life saving therapy is another's pulmonary embolism without clinical benefit. Until such time as cancer patients are selected for therapies predicated upon their own unique biology, we will confront one Avastin after another.

The solution to this problem is to investigate the VEGF targeting agents in each individual patient's tissue culture, alone and in combination with other drugs, to gauge the likelihood that vascular targeting will favorably influence each patient's outcome.

[gdpawel]

Many 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.

Source: Cell Function Analysis