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Hepatic Toxicities Associated with the Use of Preoperative Systemic Therapy in Patients with Metastatic Colorectal Adenocarcinoma to the Liver

Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA

Key Words. Colorectal cancer • Liver metastases • Chemotherapy • Targeted agents • Hepatic toxicity

Correspondence: Correspondence: Andrew X. Zhu, M.D., Ph.D., Tucker Gosnell Center for Gastrointestinal Cancers, Massachusetts General Hospital Cancer Center, Harvard Medical School, Lawrence House/POB 232, 55 Fruit Street, Boston, Massachusetts, USA. Telephone: 617-724-0786; Fax: 617-724-3166; e-mail: azhu{at}partners.org

Received July 14, 2009; accepted for publication October 1, 2009.

James M. Cleary: None; Kenneth T. Tanabe: Consultant/advisory role: American Society of Clinical Oncology; Honoraria: Sanofi-Aventis, Institute for Medical Education and Research; Research funding/contracted research: Pfizer, AstraZeneca; Gregory Y. Lauwers: None; Andrew X. Zhu: Advisory board: Genentech (bevacizumab), Bayer (sorafenib).

The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the independent peer reviewers.

Colorectal cancer patients with isolated liver metastasis are potentially cured with surgical resection. Recent advances in systemic chemotherapy have increased the ability to convert unresectable metastatic liver lesions to resectable lesions. The cost in toxicity of these therapeutic advances is increasingly being recognized. Numerous reports have demonstrated an association between irinotecan and steatohepatitis as well as between oxaliplatin and sinusoidal dilation. In this review, we summarize the current clinical experience with these hepatic toxicities and discuss the role they play in determining postoperative morbidity. We also review emerging safety data regarding the use of bevacizumab and cetuximab. Finally, we give specific clinical examples of how multidisciplinary teams can best manage patients receiving preoperative chemotherapy for potentially resectable liver metastases.