Study for the efficacy of'Metronomic chemotherapy' agains the gynecological cancers

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Recently proposed' Metronomic chemotherapy' is the new therapy using repeated administration of low dose anticancer drugs to induce' tumor dormancy state' without serious side effects against even drug-resistant tumors, based on the background that vascular endothelial cells are reproducibly susceptible to even small amount of drugs. In this study, we conducted animal experiments and clinical trials to evaluate the efficacy of metronomic chemotherapy on the gynecologic cancers. Mice bearing a paclitaxel-resistant tumor of human ovarian cancer were treated by divided-low dose or single-high dose administration of paclitaxel, and the tumor growth was more inhibited in the mice treated by the former. The toxicity was obviously mild in the mice administered by the divided-low dose. Therefore, metronomic chemotherapy seemed to be able to inhibit the tumor growth in spite of a mild side effect against drug-resistant tumors. As this reason, the divided-low dose administration of paclitaxel was found to inhibit neovascularization better than the single-high dose administration, by the experiment to evaluate the neovascularity into Matrigel. Similar results were obtained by the other anticancer drugs of docetaxel and irinotecan. Based on the theory of metronomic chemotherapy, we conducted a clinical trial of the tumor dormancy therapy by the divided-low dose anticancer drugs administered with an individualized maximum repeatable dose(iMRD). After IRB approval until now, 42 ovarian and 29 cervical cancer patients of intractable recurred cases were introduced to this study, and good QOL and relatively long TTP(time to progression) were obtained. Although the number of case is small and the follow-up period is short, the efficacy of tumor dormancy therapy applied by metronomic chemotherapy was suggested.