[Lani]

Carolyn S--this is tiny tiny dose chemotherapy, but given DAILY without any breaks. It has antiangiogenic effects --and part of that seems to be due to minimizing circulating endothelial progenitor cells which are necessary to form new blood vessels for the tumor.

It seems to work better than just Avastin or inhibitors of angiogenic growth factors, as they seem to leave a rim of unaffected tumor which regrows even faster than the tumor did before..

see except Rich posted earlier today under articles:
Mol Cancer Ther. 2009 Oct;8(10):2872-81.
Low-dose metronomic cyclophosphamide combined with vascular disrupting therapy induces potent antitumor activity in preclinical human tumor xenograft models.

Daenen LG, Shaked Y, Man S, Xu P, Voest EE, Hoffman RM, Chaplin DJ, Kerbel RS.
Molecular and Cell Biology Research, Sunnybrook Health Sciences Centre, University of Toronto, Ontario, Canada.
Vascular disrupting agents preferentially target the established but abnormal tumor vasculature, resulting in extensive intratumoral hypoxia and cell death. However, a rim of viable tumor tissue remains from which angiogenesis-dependent regrowth can occur, in part through the mobilization and tumor colonization of circulating endothelial progenitor cells (CEP). Cotreatment with an agent that blocks CEPs, such as a vascular endothelial growth factor pathway-targeting biological antiangiogenic drug, results in enhanced antitumor efficacy. We asked whether an alternative therapeutic modality, low-dose metronomic chemotherapy, could achieve the same result given its CEP-targeting effects. We studied the combination of the vascular disrupting agent OXi4503 with daily administration of CEP-inhibiting, low-dose metronomic cyclophosphamide to treat primary orthotopic tumors with the use of the 231/LM2-4 breast cancer cell line and MeWo melanoma cell line. In addition, CEP mobilization and various tumor characteristics were assessed. We found that daily p.o. low-dose metronomic cyclophosphamide was capable of preventing the CEP spike and tumor colonization induced by OXi4503. This was associated with a decrease in the tumor rim and marked suppression of primary 231/LM2-4 growth in nude as well as severe combined immunodeficient mice. Similar results were found in MeWo-bearing nude mice. The delay in tumor growth was accompanied by significant decreases in microvessel density, perfusion, and proliferation, and a significant increase in tumor cell apoptosis. No overt toxicity was observed. The combination of OXi4503 and metronomic chemotherapy results in prolonged tumor control, thereby expanding the list of therapeutic agents that can be successfully integrated with metronomic low-dose chemotherapy.

PMID: 19825805

Metronomic chemotherapy seems to get around that problem--it seems to work for colon cancer too and maybe even melanoma.

Go to Pub Med and put in Kerbel R and look at some of the abstracts and/or articles.

Food for thought