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Hepatic Resection After Rescue Cetuximab Treatment for Colorectal Liver Metastases Previously Refractory to Conventional Systemic Therapy

René Adam, Thomas Aloia, Francis Lévi, Dennis A. Wicherts, Robbert J. de Haas, Bernard Paule, Marie-Pierre Bralet, Mohamed Bouchahda, David Machover, Michel Ducreux, Vincent Castagne, Daniel Azoulay, Denis Castaing

From the Centre Hépato-Biliaire and the Departments of Medical Oncology, Pathology, and Pharmacy, Assistance Publique-Hôpitaux de Paris; University Paris-Sud, UMR-S 785, Inserm, Unité 785; and Inserm, Biological Rhythms and Cancers, Unité 776, Villejuif, France

Address reprint requests to René Adam, MD, PhD, Paul Brousse Hospital, 12 Avenue Paul Vaillant Couturier, Villejuif, France 94800; e-mail: rene.adam{at}pbr.aphp.fr

Purpose In patients with unresectable colorectal liver metastases (CLM) resistant to first-line chemotherapy, the impact of cetuximab therapy on resectability is unknown. This study was performed to determine the post-cetuximab resectability rate and to examine postoperative outcomes for these heavily pretreated patients.

Patients and Methods From February 2004 to April 2006, we evaluated 151 patients with unresectable CLM resistant to initial chemotherapy and subsequently treated with systemic cetuximab. Resectability rates, patient outcomes, and tumoral and nontumoral liver pathology were assessed.

Results A total of 27 patients underwent surgery after a median of six cycles of cetuximab + irinotecan (20 of 27), oxaliplatin (four of 27), or both (one of 27). Eighteen patients (67%) had experienced treatment failure after at least two lines of chemotherapy before cetuximab. Twenty-five of the 27 patients who had surgery underwent hepatectomy: nine of 133 patients who were treated completely at our institution (resectability rate, 7%) and 16 of 18 patients who were referred from other institutions after systemic cetuximab therapy. Postoperative mortality was 3.7% (one of 27), with a complication rate of 50%. Histopathologic liver abnormalities were found in nine patients (36%), without specific lesions attributable to cetuximab. After median follow-up of 16 months, 23 of 25 patients who underwent resection (92%) were alive, and 10 patients (40%) were disease free. Median overall (OS) and progression-free survival (PFS) from initiation of cetuximab therapy were 20 and 13 months, respectively.

Conclusion For CLM refractory to conventional chemotherapy, combination therapy with cetuximab increases resectability rates without increasing operative mortality or liver injury. The median OS and PFS of 20 and 13 months, respectively, suggest that this novel oncosurgical strategy benefits patients with previously refractory disease who respond subsequently to cetuximab.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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