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Metronomic Chemotherapy for Metastatic Breast Cancer Treatment: Clinical and Preclinical Data between Lights and Shadows

Metronomic chemotherapy (mCHT), defined as continuous administration of low-dose chemotherapeutic agents with no or short regular treatment-free intervals, was first introduced to the clinic in international guidelines in 2017, and, since then, has become one of the available strategies for the trea...

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Autores principales: Cazzaniga, Marina Elena, Capici, Serena, Cordani, Nicoletta, Cogliati, Viola, Pepe, Francesca Fulvia, Riva, Francesca, Cerrito, Maria Grazia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9410269/
https://www.ncbi.nlm.nih.gov/pubmed/36012949
http://dx.doi.org/10.3390/jcm11164710
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author Cazzaniga, Marina Elena
Capici, Serena
Cordani, Nicoletta
Cogliati, Viola
Pepe, Francesca Fulvia
Riva, Francesca
Cerrito, Maria Grazia
author_facet Cazzaniga, Marina Elena
Capici, Serena
Cordani, Nicoletta
Cogliati, Viola
Pepe, Francesca Fulvia
Riva, Francesca
Cerrito, Maria Grazia
author_sort Cazzaniga, Marina Elena
collection PubMed
description Metronomic chemotherapy (mCHT), defined as continuous administration of low-dose chemotherapeutic agents with no or short regular treatment-free intervals, was first introduced to the clinic in international guidelines in 2017, and, since then, has become one of the available strategies for the treatment of advanced breast cancer (ABC). Despite recent successes, many unsolved practical and theoretical issues remain to be addressed. The present review aims to identify the “lights and shadows” of mCHT in preclinical and clinical settings. In the preclinical setting, several findings indicate that one of the most noticeable effects of mCHT is on the tumor microenvironment, which, over the last twenty years, has been demonstrated to be pivotal in supporting tumor cell survival and proliferation. On the other hand, the direct effects on tumor cells have been less well-defined. In addition, critical items to be addressed are the lack of definition of an optimal biological dose (OBD), the method of administration of metronomic schedules, and the recognition and validation of predictive biomarkers. In the clinical context—where mCHT has mainly been used in a metastatic setting—low toxicity is the most well-recognised light of mCHT, whereas the type of study design, the absence of randomised trials and uncertainty in terms of doses and drugs remain among the shadows. In conclusion, growing evidence indicates that mCHT is a suitable treatment option for selected metastatic breast cancer (MBC) patients. Moreover, given its multimodal mechanisms of action, its addition to immunological and targeted therapies might represent a promising new approach to the treatment of MBC. More preclinical data are needed in this regard, which can only be obtained through support for translational research as the key link between basic science and patient care.
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spelling pubmed-94102692022-08-26 Metronomic Chemotherapy for Metastatic Breast Cancer Treatment: Clinical and Preclinical Data between Lights and Shadows Cazzaniga, Marina Elena Capici, Serena Cordani, Nicoletta Cogliati, Viola Pepe, Francesca Fulvia Riva, Francesca Cerrito, Maria Grazia J Clin Med Review Metronomic chemotherapy (mCHT), defined as continuous administration of low-dose chemotherapeutic agents with no or short regular treatment-free intervals, was first introduced to the clinic in international guidelines in 2017, and, since then, has become one of the available strategies for the treatment of advanced breast cancer (ABC). Despite recent successes, many unsolved practical and theoretical issues remain to be addressed. The present review aims to identify the “lights and shadows” of mCHT in preclinical and clinical settings. In the preclinical setting, several findings indicate that one of the most noticeable effects of mCHT is on the tumor microenvironment, which, over the last twenty years, has been demonstrated to be pivotal in supporting tumor cell survival and proliferation. On the other hand, the direct effects on tumor cells have been less well-defined. In addition, critical items to be addressed are the lack of definition of an optimal biological dose (OBD), the method of administration of metronomic schedules, and the recognition and validation of predictive biomarkers. In the clinical context—where mCHT has mainly been used in a metastatic setting—low toxicity is the most well-recognised light of mCHT, whereas the type of study design, the absence of randomised trials and uncertainty in terms of doses and drugs remain among the shadows. In conclusion, growing evidence indicates that mCHT is a suitable treatment option for selected metastatic breast cancer (MBC) patients. Moreover, given its multimodal mechanisms of action, its addition to immunological and targeted therapies might represent a promising new approach to the treatment of MBC. More preclinical data are needed in this regard, which can only be obtained through support for translational research as the key link between basic science and patient care. MDPI 2022-08-12 /pmc/articles/PMC9410269/ /pubmed/36012949 http://dx.doi.org/10.3390/jcm11164710 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Cazzaniga, Marina Elena
Capici, Serena
Cordani, Nicoletta
Cogliati, Viola
Pepe, Francesca Fulvia
Riva, Francesca
Cerrito, Maria Grazia
Metronomic Chemotherapy for Metastatic Breast Cancer Treatment: Clinical and Preclinical Data between Lights and Shadows
title Metronomic Chemotherapy for Metastatic Breast Cancer Treatment: Clinical and Preclinical Data between Lights and Shadows
title_full Metronomic Chemotherapy for Metastatic Breast Cancer Treatment: Clinical and Preclinical Data between Lights and Shadows
title_fullStr Metronomic Chemotherapy for Metastatic Breast Cancer Treatment: Clinical and Preclinical Data between Lights and Shadows
title_full_unstemmed Metronomic Chemotherapy for Metastatic Breast Cancer Treatment: Clinical and Preclinical Data between Lights and Shadows
title_short Metronomic Chemotherapy for Metastatic Breast Cancer Treatment: Clinical and Preclinical Data between Lights and Shadows
title_sort metronomic chemotherapy for metastatic breast cancer treatment: clinical and preclinical data between lights and shadows
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9410269/
https://www.ncbi.nlm.nih.gov/pubmed/36012949
http://dx.doi.org/10.3390/jcm11164710
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