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Investigational New Drugs

, Volume 35, Issue 3, pp 359–374 | Cite as

Current achievements and future perspectives of metronomic chemotherapy

  • Adriana RomitiEmail author
  • Rosa Falcone
  • Michela Roberto
  • Paolo Marchetti
REVIEW

Summary

In recent years, many anticancer drugs have been tested at metronomic dosages for a variety of tumours. Mechanisms of action attributed to metronomic chemotherapy (MCT) include antiangiogenesis, immunomodulation, direct inhibition of tumour growth, effect on tumour initiating cells and the modulation of clonal evolution. An active clinical research, aimed at testing MCT in several cancers, has been conducted over the past 15 years. However, because the majority of available results come from earlier phase II studies, mainly performed in the area of breast cancer (BC), it is clear that there are areas still to be investigated. We considered current studies dealing with MCT according to the clinical setting of patients. Despite a certain degree of overlap, we were able to identify four main clinical indications for MCT: refractory disease and frailty of patients, advanced stage disease (requiring first and second-line therapy), early stage disease and maintenance therapy after induction chemotherapy. In addition, a section of this review has been addressed to the combination of MCT with immunotherapy following the growing interest in the reinstatement of immune-surveillance. Crucial questions, such as the definition of optimal schedules of continuously delivered, low-dose chemotherapy and the recognition and validation of predictive biomarkers, need to be further addressed. Moreover, comparisons with the best supportive care are especially lacking and thus urgently awaited to establish the key role of MCT in the care of pretreated and frail patients. Maintenance therapy promises to be one of the most worthwhile developments for MCT. Currently, several combination strategies with standard chemotherapy, target agents or immunotherapy are under investigation but further efforts are needed to fill the gaps of knowledge in this field.

Keywords

Low-dose chemotherapy Metronomic chemotherapy Elderly Immunotherapy Predictive biomarkers 

Notes

Compliance with ethical standards

Funding

None.

Conflict of interest

Adriana Romiti declares that she has no conflict of interest. Rosa Falcone declares that she has no conflict of interest. Michela Roberto declares that she has no conflict of interest. Paolo Marchetti declares that he has no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Adriana Romiti
    • 1
  • Rosa Falcone
    • 1
  • Michela Roberto
    • 1
  • Paolo Marchetti
    • 1
  1. 1.Clinical and Molecular Medicine Department, Sapienza UniversitySant’Andrea HospitalRomeItaly

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