title: Metronomic chemotherapy and nanocarrier platforms.
abstract: The therapeutic concept of administering chemotherapeutic agents continuously at lower doses, relative to the maximum tolerated dose (MTD) without drug-free breaks over extended periods -known as "metronomic chemotherapy"- is a promising approach for anti-angiogenic cancer therapy. In comparison with MTD chemotherapy regimens, metronomic chemotherapy has demonstrated reduced toxicity. However, as a monotherapy, metronomic chemotherapy has failed to provide convincing results in clinical trials. Therapeutic approaches including combining the anti-angiogenic "metronomic" therapy with conventional radio-/chemo-therapy and/or targeted delivery of chemotherapeutic agents to tumor tissues via their encapsulation with nanocarrier-based platforms have proven to potentiate the overall therapeutic outcomes. In this review, therefore, we focused on the mutual contribution made by nanoscale drug delivery platforms to the therapeutic efficacy of metronomic-based chemotherapy. In addition, the influence that the dosing schedule has on the overall therapeutic efficacy of metronomic chemotherapy is discussed.
authors.affiliation: Department of Pharmacokinetics and Biopharmaceutics, Institute of Medical Biosciences, Tokushima University, 1-78-1, Sho-machi, Tokushima 770-8505, Japan; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt; Department of Pharmaceutics, Faculty of Pharmacy, Hail University, Hail 2440, Saudi Arabia.
authors.forename: Amr S
authors.initials: AS
authors.lastname: Abu Lila
authors.affiliation: Department of Pharmacokinetics and Biopharmaceutics, Institute of Medical Biosciences, Tokushima University, 1-78-1, Sho-machi, Tokushima 770-8505, Japan. Electronic address: ishida@tokushima-u.ac.jp.
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Ishida
mesh_terms: D059250:Administration, Metronomic; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D006801:Humans; D020714:Maximum Tolerated Dose; D050997:Nanomedicine / Q000379:methods*; D053758:Nanoparticles; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology
chemical_list: D020533:Angiogenesis Inhibitors; D004337:Drug Carriers
keywords: Dosing schedule; Liposomes; Maximum tolerated dose; Metronomic chemotherapy; Nanoparticles; Tumor priming