CourtneyL
Just wanted to point out something about high dose (dose intense) protocol. Maybe this is what Trish had been thinking of by "pulse" doses.
Many chemotherapy drugs, in addition to killing tumor cells, also fight angiogenesis. However, the anti-angiogenic effects of dose-intense (high-dose) therapy may be masked and marginalized by the way it is usually administered. There are generally long breaks between drug administration that are necessary to allow the patient to recover from the harmful side effects of treatment.
The main targets of dose-intense chemotherapy are presumed to be proliferating tumor cells. The main targets of dense-dense (low-dose) chemotherapy are the endothelial cells of the growing vasculature of a tumor. In other words, chemotherapeutics can be used as anti-angiogenic agents.
When administering both anti-tumor and anti-angiogenesis drugs, the endothelial cells (involved in angiogenessis) are the first in the tumor to undergo cell death (apoptosis).
However, this anti-angiogenic effect does not translate into a significant therapeutic benefit because the damage to the vasculature of the tumor can be largely repaired during the long rest and recovery periods between successive cycles of therapy. Perhaps, lowering the dose of drugs administered with each administration? The more frequent, regular, lower-dose therapy can have an impressive anti-angiogenic and anti-tumor effects.
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. Too much/too aggressive chemotherapy can shorten as much as it can prolong life.
Lastly, Tykerb can enhance the antivascular activity of Avastin. There was a slide presentation at the ASCO Breast Cancer Symposium on September 5, 2008.
http://www.asco.org/ASCOv2/Meetings/...stractID=40418
http://weisenthal.org/Weisenthal_ASCO.pdf (large download)
Greg