Metronomic chemotherapy, the practice of using low-dose, continuous administration of an anticancer agent to achieve cytotoxic effects in the endothelial cells of a tumor’s growing neovasculature, is still little more than a curiosity in today’s clinical practice. Since the concept was first investigated by Polverini & Novak (1986), most common cancer chemotherapy agents, from all major drug classes, have shown some antiangiogenic activity. Doy (lung), PC3 (prostate), MiaPaCa2 (pancreatic) and HT-29 (colon) cancer cells were subcutaneously xenografted into NIH Swiss nude mice and the tumors allowed to grow to between 250 and 400mm3. Thereafter, water was substituted for a dilute solution designed to administer a continuous low dose of oral drug to each mouse in the cage. When cyclophosphamide, an alkylating agent and a very popular chemotherapeutic drug, was administered at 50 mg/kg/day, it displayed the ability to stabilize tumor size, compared to controls where uncontrolled growth was observed. 5-Fluorouracil used under continuous oral administration had very little observable effect on tumor size when used at either 10 or 20 mg/kg/day. Administration of other chemotherapeutic agents either as metronomic agents or as chemotherapeutics to supplement metronomic therapy is currently under investigation. Using a drug, such as 9-nitrocamptothecin, at therapeutic concentrations in addition to metronomic administration of another drug can be used as a powerful tool to eradicate cancers and to maintain the animals tumor-free thereafter. Polverini PJ, Novak RF. Inhibition of angiogenesis by the antineoplastic agents mitoxantrone and bisantrene. Biochem. Biophys. Res. Commun. 1986; 140: 901-907.
[Proc Amer Assoc Cancer Res, Volume 45, 2004]