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01-01-2010

Impact of Preoperative Bevacizumab on Complications After Resection of Colorectal Liver Metastases: Case-Matched Control Study

Authors: Mahfud Mahfud, Stefan Breitenstein, Ashraf Mohammad El-Badry, Milo Puhan, Andreas Rickenbacher, Panagiotis Samaras, Patrick Pessaux, Santiago Lopez-Ben, Daniel Jaeck, Joan Figueras, Pierre Alain-Clavien

Published in: World Journal of Surgery | Issue 1/2010

Abstract

Background

Chemotherapy may increase postoperative morbidity and mortality after liver surgery. Especially bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), could have a detrimental effect. To assess the impact of neoadjuvant bevacizumab on clinical outcome after hepatectomy for colorectal liver metastases (CRLMs) this case-matched control study was initiated.

Methods

The multicentric data collection was performed in the Swiss HPB Center of the University Hospital Zurich (CH), the Department of Digestive Surgery and Transplantation Strasbourg (F), and the Division of Hepato-biliary-pancreatic surgery of “Josep Tureta” Hospital Girona (E). Consecutive patients operated onbetween July 2005 and December 2007 due to CRLMs who received neoadjuvant chemotherapy were assessed. Patients were divided in two groups: group A had neoadjuvant chemotherapy with bevacicumab, and group B had it without bevacizumab.

Results

No differences in overall morbidity (56 vs. 40% in the bevacizumab and control groups, respectively, p = 0.23) or mortality could be documented. Similarly, the incidence of severe postoperative complications was not statistically different between the bevacizumab and control groups (31 and 18%, respectively, p = 0.31). Wound complications were comparable (11% in the bevacizumab group compared and 9% in the control group, p = 1.00). However, bevacizumab was associated with a significantly decreased incidence of postoperative hepatic insufficiency (7 vs. 20%, p = 0.03).

Conclusions

No impact on the incidence or severity of complications by bevacizumab could be shown. Bevacizumab may even reduce the incidence of liver failure after liver surgery.

Bismuth H, Adam R, Levi F et al (1996) Resection of nonresectable liver metastases from colorectal cancer after neoadjuvant chemotherapy. Ann Surg 224:509–520, discussion 520–502CrossRefPubMed

Adam R, Avisar E, Ariche A et al (2001) Five-year survival following hepatic resection after neoadjuvant therapy for nonresectable colorectal. Ann Surg Oncol 8:347–353CrossRefPubMed

Adam R, Delvart V, Pascal G et al (2004) Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival. Ann Surg 240:644–657, discussion 657–648CrossRefPubMed

Poston GJ, Adam R, Alberts S et al (2005) OncoSurge: a strategy for improving resectability with curative intent in metastatic colorectal cancer. J Clin Oncol 23:7125–7134CrossRefPubMed

Karoui M, Penna C, Amin-Hashem M et al (2006) Influence of preoperative chemotherapy on the risk of major hepatectomy for colorectal liver metastases. Ann Surg 243:1–7CrossRefPubMed

Willett CG, Boucher Y, di Tomaso E et al (2004) Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med 10:145–147CrossRefPubMed

Hurwitz H, Fehrenbacher L, Novotny W et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335–2342CrossRefPubMed

Ellis LM (2006) Mechanisms of action of bevacizumab as a component of therapy for metastatic colorectal cancer. Semin Oncol 33:S1–S7CrossRefPubMed

Wey JS, Fan F, Gray MJ et al (2005) Vascular endothelial growth factor receptor-1 promotes migration and invasion in pancreatic carcinoma cell lines. Cancer 104:427–438CrossRefPubMed

10.

Hicklin DJ, Ellis LM (2005) Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 23:1011–1027CrossRefPubMed

11.

Hurwitz H (2004) Integrating the anti-VEGF-A humanized monoclonal antibody bevacizumab with chemotherapy in advanced colorectal cancer. Clin Colorectal Cancer 4(Suppl 2):S62–S68CrossRefPubMed

12.

Giantonio BJ, Catalano PJ, Meropol NJ et al (2007) Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 25:1539–1544CrossRefPubMed

13.

Saltz LB, Clarke S, Diaz-Rubio E et al (2008) Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 26:2013–2019CrossRefPubMed

14.

Rubbia-Brandt L, Audard V, Sartoretti P et al (2004) Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Ann Oncol 15:460–466CrossRefPubMed

15.

Vauthey JN, Pawlik TM, Ribero D et al (2006) Chemotherapy regimen predicts steatohepatitis and an increase in 90-day mortality after surgery for hepatic colorectal metastases. J Clin Oncol 24:2065–2072CrossRefPubMed

16.

Aloia T, Sebagh M, Plasse M et al (2006) Liver histology and surgical outcomes after preoperative chemotherapy with fluorouracil plus oxaliplatin in colorectal cancer liver metastases. J Clin Oncol 24:4983–4990CrossRefPubMed

17.

Ribero D, Wang H, Donadon M et al (2007) Bevacizumab improves pathologic response and protects against hepatic injury in patients treated with oxaliplatin-based chemotherapy for colorectal liver metastases. Cancer 110:2761–2767CrossRefPubMed

18.

Morris-Stiff G, Tan YM, Vauthey JN (2008) Hepatic complications following preoperative chemotherapy with oxaliplatin or irinotecan for hepatic colorectal metastases. Eur J Surg Oncol 34:609–614PubMed

19.

Clavien PA, Petrowsky H, DeOliveira ML et al (2007) Strategies for safer liver surgery and partial liver transplantation. N Engl J Med 356:1545–1559CrossRefPubMed

20.

Fernando NH, Hurwitz HI (2003) Inhibition of vascular endothelial growth factor in the treatment of colorectal cancer. Semin Oncol 30:39–50PubMed

21.

Redaelli CA, Semela D, Carrick FE et al (2004) Effect of vascular endothelial growth factor on functional recovery after hepatectomy in lean and obese mice. J Hepatol 40:305–312CrossRefPubMed

22.

D’Angelica M, Kornprat P, Gonen M et al (2007) Lack of evidence for increased operative morbidity after hepatectomy with perioperative use of bevacizumab: a matched case-control study. Ann Surg Oncol 14:759–765CrossRefPubMed

23.

Reddy SK, Morse MA, Hurwitz HI et al (2008) Addition of bevacizumab to irinotecan- and oxaliplatin-based preoperative chemotherapy regimens does not increase morbidity after resection of colorectal liver metastases. J Am Coll Surg 206:96–106CrossRefPubMed

24.

Kesmodel SB, Ellis LM, Lin E et al (2008) Preoperative bevacizumab does not significantly increase postoperative complication rates in patients undergoing hepatic surgery for colorectal cancer liver metastases. J Clin Oncol 26:5254–5260CrossRefPubMed

25.

Culy C (2005) Bevacizumab: antiangiogenic cancer therapy. Drugs Today (Barc) 41:23–36CrossRef

26.

Dindo D, Demartines N, Clavien PA (2004) Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240:205–213CrossRefPubMed

27.

Balzan S, Belghiti J, Farges O et al (2005) The “50–50 criteria” on postoperative day 5: an accurate predictor of liver failure and death after hepatectomy. Ann Surg 242:824–828, discussion 828–829CrossRefPubMed

28.

Couinaud C (1956) Contribution of anatomical research to liver surgery. Fr Med 19:5–12

29.

Strasberg SM (1997) Terminology of liver anatomy and liver resections: coming to grips with hepatic Babel. J Am Coll Surg 184:413–434PubMed

30.

D’Agostino RB Jr (1998) Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med 17:2265–2281CrossRefPubMed

31.

Abbadessa G, Vogiatzi P, Rimassa L et al (2007) Antiangiogenic drugs currently used for colorectal cancer: what other pathways can we target to prolong responses? Drug News Perspect 20:307–313CrossRefPubMed

32.

Parikh AA, Gentner B, Wu TT et al (2003) Perioperative complications in patients undergoing major liver resection with or without neoadjuvant chemotherapy. J Gastrointest Surg 7:1082–1088CrossRefPubMed

33.

Fernandez FG, Ritter J, Goodwin JW et al (2005) Effect of steatohepatitis associated with irinotecan or oxaliplatin pretreatment on resectability of hepatic colorectal metastases. J Am Coll Surg 200:845–853CrossRefPubMed

34.

Nakano H, Oussoultzoglou E, Rosso E et al (2008) Sinusoidal injury increases morbidity after major hepatectomy in patients with colorectal liver metastases receiving preoperative chemotherapy. Ann Surg 247:118–124CrossRefPubMed

35.

Deleve LD, Wang X, Tsai J, Kanel G et al (2003) Sinusoidal obstruction syndrome (veno-occlusive disease) in the rat is prevented by matrix metalloproteinase inhibition. Gastroenterology 125:882–890CrossRefPubMed

36.

Fong Y, Bentrem DJ (2006) CASH (chemotherapy-associated steatohepatitis) costs. Ann Surg 243:8–9CrossRefPubMed

37.

Nordlinger B, Sorbye H, Glimelius B et al (2008) Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet 371:1007–1016CrossRefPubMed

38.

Verheul HM, Lolkema MP, Qian DZ et al (2007) Platelets take up the monoclonal antibody bevacizumab. Clin Cancer Res 13:5341–5347CrossRefPubMed

39.

Ma L, Elliott SN, Cirino G et al (2001) Platelets modulate gastric ulcer healing: role of endostatin and vascular endothelial growth factor release. Proc Natl Acad Sci U S A 98:6470–6475CrossRefPubMed

40.

Scappaticci FA, Fehrenbacher L, Cartwright T et al (2005) Surgical wound healing complications in metastatic colorectal cancer patients treated with bevacizumab. J Surg Oncol 91:173–180CrossRefPubMed

41.

Gruenberger B, Tamandl D, Schueller J et al (2008) Bevacizumab, capecitabine, and oxaliplatin as neoadjuvant therapy for patients with potentially curable metastatic colorectal cancer. J Clin Oncol 26:1830–1835CrossRefPubMed

42.

Kabbinavar FF, Schulz J, McCleod M et al (2005) Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial. J Clin Oncol 23:3697–3705CrossRefPubMed

43.

Ferrara N, Hillan KJ, Novotny W (2005) Bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody for cancer therapy. Biochem Biophys Res Commun 333:328–335CrossRefPubMed

Title: Impact of Preoperative Bevacizumab on Complications After Resection of Colorectal Liver Metastases: Case-Matched Control Study
Authors: Mahfud Mahfud
Stefan Breitenstein
Ashraf Mohammad El-Badry
Milo Puhan
Andreas Rickenbacher
Panagiotis Samaras
Patrick Pessaux
Santiago Lopez-Ben
Daniel Jaeck
Joan Figueras
Pierre Alain-Clavien
Publication date: 01-01-2010
Publisher: Springer-Verlag
Published in: World Journal of Surgery / Issue 1/2010
Print ISSN: 0364-2313
Electronic ISSN: 1432-2323
DOI: https://doi.org/10.1007/s00268-009-0251-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Impact of Preoperative Bevacizumab on Complications After Resection of Colorectal Liver Metastases: Case-Matched Control Study

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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