|
|
|
|
|
|
|
|
|
|
Further evidence that Avastin improved progression free survival in women with ovarian cancer was presented by researchers at the European Society of Medical Oncology (ESMO) congress in Milan, Italy. A new Phase III Avastin (ICON7) trial showed again that women with chemotherapy-naïve ovarian cancer had better progression free survival compared to women only on chemotherapy. A chemotherapy-naïve patient is one who has never received chemotherapy.
ICON7 is the second Phase III clinical trial on Avastin for ovarian cancer treatment. It compared chemotherapy-naïve women on Avastin plus chemotherapy versus similar patients on just chemotherapy. PFS (progression free survival) was approximately 27% better among those in the Avastin group; this corresponded to a 21% drop in the chances of cancer progression to death, the investigators explained. GOG0218, the first Phase III pivotal Avastin trial, had demonstrated earlier this year that Avastin plus chemotherapy and then alone gave ovarian cancer patients a 54% higher chance of progression free survival compared to women on chemotherapy alone.The Avastin dosage was smaller in the ICON7 trial, which also lasted less time....cont'd
Tumor growth is dependent on angiogenesis. Angiogenesis is dependent on vascular endothelial growth factor (VEGF). Avastin 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.
ReplyDeleteIf the anti-angiogenesis drugs work the way they are supposed to work they block the activity of VEGF, to prevent the growth of new capillaries into the tumor and thereby sustain tumor growth.
Perhaps Avastin "sensitive" tumors secrete relatively low levels of VEGF. Tumors which secrete relatively low levels of VEGF might be more susceptible to an agent which works by blocking VEGF.
Avastin blocks VEGF and causes existing microcapillaries to die. This is what is measured with the AngioRx Assay (which simultaneously measures direct antitumor activity and antivascular activity), death of existing endothelial (and associated) cells.
The rationale underlying the use of anti-angiogenesis drugs against ovarian cancer is that (1) VEGF pathways are strongly associated with the development of malignant ascites, malignant pleural effusions and carcinomatosis, and (2) both VEGF receptors and VEGF ligands can be over-expressed in ovarian cancer.
Single-agent Avastin has not been showing up being very productive in cell function analysis. According to clinical oncologists involved with cell culture assay testing, Avastin appears to better deliver the effects of other classes of drugs. In other words, Avastin facilitates vascular access of cytotoxics to tumors. Just as the GOG0218 trial results showed.