Anti-angiogenesis drugs work by blocking the activity of VEGF to prevent the growth of new capillaries into the tumor and thereby sustain tumor growth. VEGF causes angiogenesis by attaching to special receptors, and this action starts a series of chemical reactions inside the cell.

Avastin (bevacizumab) directly binds to VEGF to directly inhibit angiogenesis. Within 24 hours of VEGF inhibition, endothelial cells have been shown to shrivel, retract, fragment and die by apoptosis. Tumors which secrete relatively low levels of VEGF might be more susceptible to an agent like Avastin which works by blocking VEGF (Avastin “sensitive” tumors). It potently inhibits the formation of new blood vessels.

There is an interesting caveat about Avastin which deals with colon cancer – gastrointestinal perforations. If Avastin is given within at least 28 days following major surgery (or before), it results in an abscess formation. This is due to the impaired wound healing induced by Avastin.

By Avastin working like it’s supposed to work, not only does it cut off blood supply to the tumor, it also cuts off blood supply to the colon entirely causing the tissue to die. Avastin can cause you to loose your colon. What’s distubring is oncologists’ comment that this is common with Avastin, but is never mentioned until it is too late.

Most bowel perforations with Avastin have been in cases where there is tumor going right through the wall of the colon. Avastin causes the tumor to melt away, leaving a hole. With Avastin, the tumor dissolves, but scar tissue won’t form because it can’t make a blood supply.

The same thing applies to bowl perforations with Avastin in advanced ovarian cancer. Advanced ovarian cancer commonly involves bowel walls. The problem is a direct result of the drug’s ability to kill tumor cells that have replaced healthy bowel tissue, leading to a dead area that then perforates.

With conventional chemotherapy, as the tumor melts away, new connective tissue forms a patch. But Avastin can inhibit the growth of capillaries into newly forming tissue, as well as in tumor tissue. If one does not have any known bowel involvement, one would probably be okay.

Many of these new “targeted” therapies often get a pass on toxicities because they are just so darn cool (Herceptin and CHF in the adjuvant setting is another example). The problem is that few drugs work the way oncologists think and few of them take the time to think through what it is they are using them for.