Elsevier

Cancer Treatment Reviews

Volume 42, January 2016, Pages 82-90
Cancer Treatment Reviews

Systematic or Meta-analysis Studies
Maintenance strategy in metastatic colorectal cancer: A systematic review

https://doi.org/10.1016/j.ctrv.2015.10.012Get rights and content

Highlights

Abstract

Purpose

Colorectal cancer is the third most common cancer in men and second in women, estimated to cause 694,000 deaths worldwide in 2012. Although 5-year survival rate of CRC has increased, inoperable metastatic colorectal cancer (mCRC) is almost always fatal. The aim of this systematic review is to outline the maintenance strategies that increase the chance and duration of survival with less toxicity and sustained quality of life.

Design

Literature search in PubMed, in American Society of Clinical Oncology (ASCO) Annual Meetings and in ASCO Gastrointestinal Symposia and European Society for Medical Oncology (ESMO) Congresses was performed. Studies conducted in adult patients were written in English language and were published in peer-reviewed journals as phase II or III randomized controlled trials (RCTs) comparing continuous chemotherapy to intermittent chemotherapy, each with or without maintenance therapy was included along with at least one of the outcomes of interest.

Results

Twenty randomized controlled trials and systematic reviews were included from Medline search, together with 4 abstracts from ASCO meetings and 2 abstracts from ESMO meetings.

Conclusion

Existing evidence-based data show that prolonged progression free survival (PFS) can be achieved with less toxic regimens compared to complete drug holidays or continued treatment. However, the impact of maintenance on overall survival is less clear. The specific data for maintenance with biological agents are evolving, while in general fluoropyrimidine based maintenance with bevacizumab is better than Bev alone or observation for PFS. Data regarding Cetuximab maintenance are less pronounced than that of Bev maintenance. Preliminary data show that erlotinib-Bev combination may be of benefit as maintenance. Although maintenance may provide significant clinical benefit in clinical studies, the optimal strategy should still be individualized.

Introduction

Colorectal cancer (CRC) is among the leading malignancies in terms of incidence and mortality worldwide. According to the 2014 World Cancer Report, it is the third most common cancer in men and second in women, estimated to cause 694,000 deaths in 2012 globally [1]. Although the 5-year survival rates of CRC is increased from 51% to 65% and more patients are diagnosed at earlier stages, half of the CRC patients will eventually develop metastasis, inoperable metastatic colorectal cancer (mCRC) is almost always fatal [2]. The increase in the number of long term survivors, considered with the burden of incurable mCRC patients emphasize the importance of palliative treatment and quality of life (QOL) and raise the question of how to achieve the optimal treatment strategy and duration.

The most active regimens used in CRC are based on fluoropyrimidines used in combination with oxaliplatin or irinotecan and with or without targeted agents such as bevacizumab, cetuximab (Cet) or panitumumab. The median overall survival (OS) of CRC patients now exceeds 33 months in phase 3 studies [3], [4], [5]. As the OS of CRC is increased, expected and exposed toxicities of the chemotherapy are also increased. In clinical practice, one of the major dose-limiting toxicity of oxaliplatin is the peripheral sensory neuropathy. Neuropathy is cumulative but usually regressive to some degree after drug discontinuation but maybe disabling [6]. Irinotecan is generally tolerated better and has less clinically relevant cumulative toxicity. Therefore, strategies to diminish the toxicity of treatments, to increase the QOL and to develop optimal strategies for longer survival are a major concern of investigators especially in patients receiving oxaliplatin based regimens, making maintenance strategies as one of the key issues in the management of mCRC.

This review will summarize the randomized controlled trials (RCTs), which include maintenance strategy in mCRC.

Section snippets

Search strategy and study identification

Literature searches in PubMed (1990 to March 2015), American Society of Clinical Oncology (ASCO) Annual Meetings (1997–2014), ASCO Gastrointestinal Symposia (GI) (2000 to 2014), and European Society for Medical Oncology (ESMO) Congresses (2000 to 2014) were performed. The selection and the writing process were completed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement [7]. The main keywords used for the search were ^maintenance^ and ^colon

Discussion and conclusion

Although colon cancer mortality has decreased over the past 30 years, there is a substantial heterogeneity in survival rates based on patient and tumor characteristics, host response factors and treatment strategy (drugs, regimens, surgical approaches and ablative therapies). As the armory of mCRC treatment increases, clinical decisions about better drug selection, optimal combination and duration of treatment, become more complicated.

To date, treatment until progression or unacceptable

Disclaimer

Ece ESIN has nothing to disclose.

Conflict of interest

Dr. Ece Esin has no conflict of interest related to the topic of the manuscript.

Prof Suayib Yalcin received honorium from Roche, Merck serono, Amgen, Novartis, Sanofi and reseach grant from Celgene.

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    1

    Ece Esin and Suayib Yalcin have equally contributed to this work.

    2

    Tel.: +90 312 305 2929; fax: +90 312 305 2905.

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