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Bevacizumab, Capecitabine, and Oxaliplatin As Neoadjuvant Therapy for Patients With Potentially Curable Metastatic Colorectal Cancer

Brigit Gruenberger, Dietmar Tamandl, Johannes Schueller, Werner Scheithauer, Christoph Zielinski, Friedrich Herbst, Thomas Gruenberger

From the Department of Oncology, Rudolfstiftung Hospital; the Department of Internal Medicine I and Cancer Center, Medical University of Vienna; and the Department of General Surgery, Medical University of Vienna, Vienna, Austria

Corresponding author: Thomas Gruenberger, MD, Department of General Surgery, Waehringer Guertel 18-20, 1090 Vienna, Austria; e-mail: thomas.gruenberger{at}meduniwien.ac.at

Purpose: Patients with colorectal cancer (CRC) and liver metastases have a poor prognosis, but can benefit from perioperative chemotherapy and disease resection. Bevacizumab improves outcomes in patients with metastatic CRC; however, its impact on surgical complications and hepatic regeneration after liver resection remains to be determined.

Patients and Methods: Fifty-six patients with metastatic CRC with liver metastases potentially curable by resection were eligible for this single-center, nonrandomized phase II trial. Eligibility criteria defined patients at high risk of early recurrence. Patients received biweekly bevacizumab plus capecitabine and oxaliplatin for six cycles. The sixth cycle of therapy did not include bevacizumab, resulting in 5 weeks between the last administration of bevacizumab and surgery.

Results: Objective response to neoadjuvant chemotherapy was achieved in 41 patients (73%). Fifty-two patients underwent liver resection including 11 with synchronous primary tumor resection. No increased intraoperative bleeding events or wound-healing complications were observed and only three patients (6%) required perioperative blood transfusions. Further surgery was necessary in a single patient. Postoperative liver function and regeneration were normal in all but one patient. No postoperative mortality occurred and morbidity was encountered in 11 patients (20%). The mean length of postoperative hospitalization was 9 days (± 4.0).

Conclusion: These data suggest that bevacizumab can be safely administered until 5 weeks before liver resection in patients with metastatic CRC without increasing the rate of surgical or wound healing complications or severity of bleeding. To our knowledge, they are also the first to show that neoadjuvant bevacizumab does not affect liver regeneration after resection.

Presented in part at the 42nd Annual Meeting of the American Society of Clinical Oncology, Atlanta, GA, 2006; the 43rd Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 1-5, 2007; the 8th World Congress on Gastrointestinal Cancer, Barcelona, Spain, June 28 to July 1, 2006; and the 31st European Society of Medical Oncology Conference, Istanbul, Turkey, September 29 to October 2, 2006.

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

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				G. Nasti, A. Ottaiano, V. Rosario Iaffaioli, M. Berretta, and P. Delrio Trials on Preoperative Chemotherapy in Resectable Colorectal Liver Metastases Need Prospective Evaluation of Predictive Factors of Response J. Clin. Oncol., August 1, 2008; 26(22): 3812 - 3813. [Full Text] [PDF]

				T. Gruenberger and B. Gruenberger In Reply J. Clin. Oncol., August 1, 2008; 26(22): 3813 - 3813. [Full Text] [PDF]

				A. J. Bilchik and J. R. Hecht Perioperative Risks of Bevacizumab and Other Biologic Agents for Hepatectomy: Theoretical or Evidence Based? J. Clin. Oncol., April 10, 2008; 26(11): 1786 - 1788. [Full Text] [PDF]