title: Pharmacokinetics of metronomic chemotherapy: a neglected but crucial aspect.
abstract: Metronomic chemotherapy describes the close, regular administration of chemotherapy drugs at less-toxic doses over prolonged periods of time. In 2015, the results of randomized phase III clinical trials demonstrated encouraging, albeit limited, efficacy benefits of metronomic chemotherapy regimens administered as adjuvant maintenance therapy for the treatment of breast cancer, or as maintenance therapy in combination with an antiangiogenic agent for metastatic colorectal cancer. Owing to the investigational nature of this approach, metronomic chemotherapy regimens are highly empirical in terms of the optimal dose and schedule for the drugs administered; therefore, greater knowledge of the pharmacokinetics of metronomic chemotherapy is critical to the future success of this treatment strategy. Unfortunately, such preclinical and clinical pharmacokinetic studies are rare. Herein, we present situations in which active drug concentrations have been achieved with metronomic schedules, and discuss their associated pharmacokinetic parameters. We summarize examples from the limited number of clinical studies in order to illustrate the importance of assessing such pharmacokinetic parameters, and discuss the influence this information can have on improving efficacy and reducing toxicity.
authors.affiliation: Divisione di Farmacologia, Dipartimento di Medicina Clinica e Sperimentale, Università di Pisa, Via Roma, 55, I-56126 Pisa, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Bocci
authors.affiliation: Sunnybrook Research Institute/Odette Cancer Centre, Biologic Sciences Platform, S-217, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada.|University of Toronto, Department of Medical Biophysics, S-217, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Kerbel
mesh_terms: D059250:Administration, Metronomic; D000477:Alkylating Agents / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology; D002166:Camptothecin / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics; D017326:Clinical Trials, Phase III as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D005544:Forecasting; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D011743:Pyrimidines / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics; D016032:Randomized Controlled Trials as Topic; D050257:Tubulin Modulators / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics
chemical_list: D000477:Alkylating Agents; D020533:Angiogenesis Inhibitors; D011743:Pyrimidines; D050257:Tubulin Modulators; C029269:5-fluoropyrimidine; D002166:Camptothecin