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First-line chemotherapy for mCRC—a review and evidence-based algorithm

Nature Reviews Clinical Oncology volume 12, pages 607–619 (2015)Cite this article

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Abstract

The response to first-line therapy is a primary determinant of outcome in patients with metastatic colorectal cancer (mCRC), for three main reasons: effective upfront therapy provides a unique opportunity to cure some patients; can be crucial in delaying disease progression and achieving symptom relief; and can improve patient eligibility for, and the effectiveness of, further treatments. In the past decade, decision-making regarding the choice of first-line therapy for mCRC has been complicated by the availability of many different options without a definitive consensus on a specific standard of care (despite major advances in categorizing predictive molecular disease subtypes). Most of the efforts of the scientific community have been directed at establishing the best biologic agent to be combined with a chemotherapy doublet, although a different branch of research has produced new data that underscore the importance of defining the optimal chemotherapy backbone. Herein, we review the key clinical trials completed in the past 10 years that have investigated and compared the use of chemotherapy doublets, triplets, and monotherapies, with or without molecularly targeted biologic agents, in the first-line treatment of patients with mCRC. Our examination of the literature led us to propose a new patient-oriented algorithm to guide clinicians' decisions on the best choice of upfront therapy for mCRC.

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Figure 1: Algorithm for personalized allocation of first-line treatments in patients with mCRC.

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  1. Unit of Medical Oncology 2, Azienda Ospedaliera-Universitaria Pisana, Via Roma 67, Pisa, 56126, Italy

    Chiara Cremolini, Marta Schirripa, Carlotta Antoniotti, Roberto Moretto, Lisa Salvatore, Gianluca Masi, Alfredo Falcone & Fotios Loupakis

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C.C. and M.S. contributed equally to the preparation of this manuscript. C.C., M.S., C.A., R.M., L.S., G.M., A.F. and F.L. contributed to researching data for the article, discussions of content, and writing and review/editing of the manuscript before submission.

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Correspondence to Fotios Loupakis.

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C.C. has received payment for consultancy and honouraria for speaking from Amgen, Bayer, and Roche. G.M. has received payment for consultancy and honouraria for speaking from Amgen, Bayer, Merck and Roche. A.F. and F.L. have received payment for consultancy and honouraria for speaking from Amgen, Bayer, Merck, Roche, and Sanofi. The other authors declare no competing interests.

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Cremolini, C., Schirripa, M., Antoniotti, C. et al. First-line chemotherapy for mCRC—a review and evidence-based algorithm. Nat Rev Clin Oncol 12, 607–619 (2015). https://doi.org/10.1038/nrclinonc.2015.129

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