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Drug Insight: gastrointestinal and hepatic adverse effects of molecular-targeted agents in cancer therapy

Nature Clinical Practice Oncology volume 5, pages 268–278 (2008)Cite this article

A Corrigendum to this article was published on 01 March 2009

Abstract

Recent advances in the understanding of molecular mechanisms of cancer have led to the development of novel compounds that target specific cancer pathways. These drugs encompass monoclonal antibodies and tyrosine and non-tyrosine kinase inhibitors, and have been approved by the FDA and the European Medicines Agency, among others, for cancer treatment. These agents are associated with several toxic effects including potentially unacceptable gastrointestinal adverse effects. Diarrhea and hepatotoxicity, the most common adverse events experienced with these treatments, can frequently lead to treatment discontinuation and consequently decreased cancer control. We review the incidence and clinical patterns of the gastrointestinal and hepatic toxic effects induced by the main molecular-targeted therapies and propose some hypotheses for the causes of each adverse event.

Key Points

  • Gastrointestinal and hepatic adverse effects are common features of molecular-targeted therapies

  • Limited data are available regarding the pathophysiology of such toxicities

  • Pathophysiological mechanisms of diarrhea mainly involve secretory diarrhea, and direct blockage of tyrosine kinases present in the intestinal epithelium

  • Pharmacokinetic interactions are often involved in hepatic toxicity

  • Hepatic and gastrointestinal adverse effects might provide insights into the mechanisms of action of molecular-targeted agents and, more widely, into the physiology of the liver and the gastrointestinal tract

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Acknowledgements

The authors thank Lorna Saint Ange and Professor Ducreux for their help in editing the manuscript. Charles P Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.

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Author notes

  1. Yohann Loriot, Gabriel Perlemuter, David Malka, Frédérique Penault-Lorca, Valérie Boige, Eric Deutsch, Christophe Massard, Jean Pierre Armand and Jean-Charles Soria: Y Loriot is a Fellow in Medical Oncology, D Malka and V Boige are members of the Gastrointestinal Oncology Unit, E Deutsch is Assistant Professor, and C Massard is a member of the Phase I Unit, all at the Institute Gustave Roussy, Villejuif, France.

  2. G Perlemuter is Professor of Hepatology at the Hôpital Antoine Béclère, Clamart Cedex.

  3. F Penault-Lorca is Professor of Pathology in the Department of Pathology, Centre Jean Perrin, Clermont–Ferrand.

  4. JP Armand is General Director of Institute Claudius Rigaud, Toulouse.

  5. JC Soria is Head of the Phase I Unit at the Institute Gustave Roussy and Professor of Medicine and Medical Oncology at Paris University XI, Paris.

Authors and Affiliations

  1. Phase I Unit–Department of Medicine, Institute Gustave Roussy, 39 Rue Camille Desmoulins, Villejuif, 94800, France

    Jean-Charles Soria

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Competing interests

JC Soria is a Consultant for Roche, sanofi-aventis and Wyeth, and also receives grant funding from Eli Lilly. D Malka is on the speakers bureau for Merck, Pfizer, Roche, sanofi-aventis and Serano, and receives grant or research support from Merck, Roche, sanofi-aventis and Serano. The other authors declared no competing interests.

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Loriot, Y., Perlemuter, G., Malka, D. et al. Drug Insight: gastrointestinal and hepatic adverse effects of molecular-targeted agents in cancer therapy. Nat Rev Clin Oncol 5, 268–278 (2008). https://doi.org/10.1038/ncponc1087

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