Recent clinical evidence on metronomic dosing in controlled clinical trials: a systematic literature review

Introduction: Metronomic dosing is used to give continuous chemotherapy at low doses. The low doses have minimal side effects and may enable cancer treatment to be remodeled toward the management of chronic disease.Methods: We searched PubMed database to obtain relevant clinical trials studying metronomic chemotherapy (MCT). Our main focus was to find controlled phase II and phase III trials.Results: This systematic review summarizes the results of 91 clinical reports focusing on randomized phase II and phase III clinical studies between 2012 and 2018. During that time, nine randomized phase II and 10 randomized phase III studies were published. In the majority of the studies, MCT was well tolerated, and major side effects were rarely seen. Altogether, 4 phase III studies and 4 randomized phase II studies presented positive results and some clinical benefit.Discussion: Most of the studies did not show significantly improved overall survival or progression-free survival. Typically, the metronomic dosing was explored in a maintenance setup and was added to other agents given within normal high doses, whereas no trial was performed challenging metronomic dosing and best supportive care in later treatment lines. Therefore, there is no definite evidence on the efficacy of single metronomic dosing and firm evidence of metronomic dosing is still missing. There is a need for further confirmation of the usefulness of this approach in clinical practice.