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Clinical overview of metronomic chemotherapy in breast cancer

Key Points

  • Metronomic chemotherapy induces disease control in patients with advanced-stage breast cancer with a lower incidence of adverse events compared with conventional maximum tolerated dose chemotherapy

  • Ideal agents to be used in metronomic chemotherapy regimens should be oral, inexpensive and well-tolerated, with no or minimal cumulative toxicity

  • Several phase III trials on metronomic chemotherapy are ongoing and might demonstrate whether this approach will remain a niche option or assume a wider acceptance and application

  • Most drugs used in a metronomic fashion have generic equivalents, are inexpensive, and available in oral form, which avoids costly hospital stays and intravenous injections

  • Metronomic chemotherapy regimens combined with molecularly targeted agents might improve the therapeutic activity and avoid industry concerns regarding the use of off-patent or cheap chemotherapy drugs

  • Metronomic protocols should be guided by molecular data as the genetic and epigenetic landscape of a given tumour can be markedly different at diagnosis, post-treatment and at relapse

Abstract

Over 15 years ago, low-dose metronomic chemotherapy was shown to induce disease control in patients with advanced-stage breast cancer with a lower incidence of adverse events compared with conventional maximum tolerated dose chemotherapy. Good response rates have been seen in heavily pre-treated patients for whom limited treatment options are available. Most patients prefer oral therapy and metronomic chemotherapy is a convenient alternative in patients with advanced-stage disease in which minimal toxicity and good tumour control are the overall aims of treatment. The addition of metronomic protocols to standard neoadjuvant chemotherapy regimens has produced promising pathological complete response rates. Ongoing trials including the SYSUCC-001 trial in patients with triple-negative breast cancer and the IBCSG 22-00 trial that is assessing a cyclophosphamide–methotrexate maintenance regimen after standard adjuvant therapy in hormone receptor-negative disease, will clarify the value of adding this approach to conventional therapies. The low cost associated with metronomic chemotherapy represents an opportunity for the utilization of this treatment option, especially in developing countries, and poses a challenge for the launch of large trials sponsored by industry. Using breast cancer as the principal example, we discuss the key clinical advances in this area, including new trial design, appropriate patient and end point selection, as well as the evolving rationale for metronomic chemotherapy combinations.

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Figure 1: Metronomic chemotherapy concept showing multiple mechanisms.

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Both authors researched the data for the article, and contributed substantially to discussion of content. Both authors wrote the article and reviewed and edited the manuscript before submission.

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Correspondence to Marco Colleoni.

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M.C. declares he receives honoraria for consultancy for AbbVie, AstraZeneca, Novartis, Pierre Fabre and Taiho Pharmaceuticals. E.M. declares no competing interests.

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Munzone, E., Colleoni, M. Clinical overview of metronomic chemotherapy in breast cancer. Nat Rev Clin Oncol 12, 631–644 (2015). https://doi.org/10.1038/nrclinonc.2015.131

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