Metronomic Antiangiogenic Chemotherapy: Questions and Answers

作者: Robert S. Kerbel , Urban Emmenegger , Shan Man , Raquel Munoz , Francesco Bertolini

DOI: 10.1007/978-3-540-33177-3_34

关键词:

摘要: Metronomic(antiangiogenic) chemo-therapy refers to the close, regular administration of low doses (non-toxic) conventional chemotherapy drugs, in absence any prolonged drug-free break periods, over long periods time, even several years. Unlike “dose-dense” and intensive it is minimally toxic thus does not usually require supportive care drugs. The preclinical antitumor effects certain metronomic regimens can be surprisingly good, especially when used combination with concurrent a targeted biologic antiangiogenic agent. It thought that basis mainly via mechanisms as result local targeting dividing endothelial cells growing tumor neovasculature, also systemic bone marrow-derived circulating progenitor (CEPs). Maximum tolerated dose (MTD) may, some circumstances, target CEPs but hemopoiesis-like proangiogenic acute CEP “rebound” occur immediately afterwards which hypothesized nullify this potential effect. Shortening or eliminating compromises robust repair process. This rebound phenomenon may help explain ability drugs such bevacizumab (Avastin®) enhance efficacy regimens, i.e., by preventing rebound. Several phase II clinical trials, randomized, have been completed, most using daily low-dose (e.g. 50 mg) oral cyclophosphamide, conjunction agent letrozole for treatment either advanced early stage breast cancer, celecoxib non-Hodgkin’ s lymphoma, encouraging results, despite obvious drawback empiricism associated dosing. However, advances are being made, both preclinically clinically, discovery surrogate markers monitor activity determine optimal dose. These include apoptotic CEPs.

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