Updated link to the above abstract:
http://meeting.ascopubs.org/cgi/cont.../15_suppl/1060
Many conventional chemotherapy drugs, in addition to killing tumor cells, also fight angiogenesis. The anti-angiogenic effects of 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.
When administering these drugs, the endothelial cells (involved in angiogenesis) 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.
The more frequent, 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.
The main targets of dose-dense 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 can be used as anti-angiogenic agents.
A Japanese trial found that ovarian cancer patients lived longer if they received smaller doses of chemotherapy weekly rather than getting larger doses every three weeks, according to results published in The Lancet.
My wife experienced this method of treatment for her stage IV ovarian cancer in 1972. She was treated with total abdominal hysterectomy and Chlorambucil (Leukeran) treatment. This postoperative chemotherapy drug is among the slowest acting and least toxic of the alkylating agents (well tolerated oral drugs).
By giving chemotherapy more often, at lower doses, it can prevent the regrowth of blood vessels that feed tumors (angiogenesis). Depression of the immune system is slow and reversible, allowing it to regenerate and contribute to recovery. A malfunctioning immune system can fail to stop the growth of cancer cells. She went twenty-four years before experiencing any recurrent ovarian cancer.
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