REVIEW ARTICLE Metronomic chemotherapy for cancer treatment: a decade of clinical studies Adriana Romiti • M. Christina Cox • Ida Sarcina • Roberta Di Rocco • Chiara D’Antonio • Viola Barucca • Paolo Marchetti Received: 10 November 2012 / Accepted: 12 February 2013 / Published online: 9 March 2013 Ó Springer-Verlag Berlin Heidelberg 2013 Abstract Purpose Over the past few years, more and more new selective molecules directed against specific cellular targets have become available for cancer therapy, leading to impressive improvements. In this evolving scenario, a new way of delivering older cytotoxic drugs has also been developing. Many studies demonstrated that several cyto- toxic drugs have antiangiogenic properties if administered frequently and at lower doses compared with standard schedules containing maximal tolerated doses (MTD). Such a new strategy, named metronomic chemotherapy, focuses on a different target: the slowly proliferating tumour endothelial cells. About 10 years ago, metronomic chemotherapy was firstly enunciated and hereafter many clinical experiences were published related to almost any cancer disease. This review analyses available studies dealing with metronomic chemotherapy and its combina- tion with several targeted agents in solid tumours. Methods A computerized literature search of MEDLINE was performed using the following search terms: metro- nomic OR ‘‘continuous low dose’’ AND chemotherapy AND cancer OR solid tumours. Results Satisfactory results have been achieved in diverse tumour types, such as breast and prostate cancer or pae- diatric sarcomas. Moreover, many studies have reported that metronomic chemotherapy determined minimal tox- icity compared to MTD chemotherapy. Overall, published series on metronomic schedules are very heterogeneous often reporting on retrospective data, while only very few studies were randomized trials. These limitations still prevent to draw definitive conclusions in diverse tumour types. Conclusions Large well-designed studies are eagerly awaited for confirming the promises of metronomic schedules and their combinations with targeted molecules. Keywords Metronomic chemotherapy Á Cancer therapy Á ‘‘Continuous low dose’’ chemotherapy Á Solid tumours Introduction Cancer therapy has impressively progressed over the past few years, with the development of targeted treatments [1]. In this new scenario, traditional cytotoxic chemotherapy has also been evolving. Both newer drug combinations and modalities of administration have been purposely tested to improve efficacy and tolerability of chemotherapies. Conventional chemotherapy administration is generally based on the concept of the maximum tolerated dose (MTD), consisting in the highest survivable (minimum lethal) dose, steered to kill as many tumour cells as pos- sible. However, this strategy, which was supported by very high cure rate in pre-clinical studies [2], requires treatment- free intervals to resume the growth of normal host cells, like the hematopoietic progenitors and the epithelial cells. Nonetheless, excluding some haematological or germinal A. Romiti (&) Á I. Sarcina Á R. Di Rocco Á C. D’Antonio Á V. Barucca Á P. Marchetti Department of Oncology, Faculty of Medicine and Psychology, Sapienza University, Sant’Andrea Hospital, Via di Grottarossa 1035-1039, 00189 Rome, Italy e-mail: adriana.romiti@tin.it M. C. Cox Department of Hematology, Faculty of Medicine and Psychology, Sapienza University, Sant’Andrea Hospital, Rome, Italy 123 Cancer Chemother Pharmacol (2013) 72:13–33 DOI 10.1007/s00280-013-2125-x