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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2013

Open Access 01-12-2013 | Review

Rechallenge therapy and treatment holiday: different strategies in management of metastatic colorectal cancer

Authors: Giuseppe Tonini, Marco Imperatori, Bruno Vincenzi, Anna Maria Frezza, Daniele Santini

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2013

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Abstract

Fluoropyrimidines, oxaliplatin, irinotecan and biologic therapies (Bevacizumab, Panitumumab, and Cetuximab) represent the backbone of metastatic colorectal cancer (CRC) treatment. The improvement in survival for mCRC patient led to two main outstanding issues: 1) there is a significant number of patients progressing beyond the third or fourth line of treatment still suitable for further therapy when enrollment into clinical trial is not possible. In this situation, the role of any therapy rechallenge (either chemotherapy alone, chemotherapy and biologic therapy or biologic therapy alone) is still not clear, particularly in patients who had previously responded, and if treatment choice is based on traditional dogma of primary and secondary resistance, rechallenge does not seem to be justified. 2) Prolonged intensive treatment is burdened from the high risk of cumulative toxicity, worsening in quality of life and a not well defined possibility of early acquired resistance.
Different hypothesis could justify the research of different strategy in treatment of mCRC:
1) Epigenetic changes might drive resistance and treatment could induce these changes. Re-expression of silenced tumor suppressive genes might resensitize tumors to therapy. It is therefore possible that a drug holiday (intermittent treatment) could allow reversion to a previous epigenetic profile. Moreover an intermittent treatment could delay acquired resistance. 2) It is plausible that tumor grows as a polyclonal mass. If it responds but then becomes resistant to one or more treatments, retreatment might be successful if changing therapies allows to that clone of cells to re-emerge. On these basis, we focused this review on the actual evidences in management of mCRC patients in terms of chemotherapy or biological therapies rechallenge and intermittent treatment. Moreover, we will discuss the potential biological mechanisms of the observed results of early clinical trials.
Appendix
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Metadata
Title
Rechallenge therapy and treatment holiday: different strategies in management of metastatic colorectal cancer
Authors
Giuseppe Tonini
Marco Imperatori
Bruno Vincenzi
Anna Maria Frezza
Daniele Santini
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2013
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/1756-9966-32-92

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