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Erschienen in: Annals of Surgical Oncology 6/2014

01.06.2014 | Colorectal Cancer

Bevacizumab Doubles the Early Postoperative Complication Rate after Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Peritoneal Carcinomatosis of Colorectal Origin

verfasst von: Clarisse Eveno, MD, PhD, Guillaume Passot, MD, Diane Goéré, MD, PhD, Philippe Soyer, MD, PhD, Etienne Gayat, MD, PhD, Olivier Glehen, MD, PhD, Dominique Elias, MD, PhD, Marc Pocard, MD, PhD

Erschienen in: Annals of Surgical Oncology | Ausgabe 6/2014

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Abstract

Background

Patients with stage IV colorectal cancer and peritoneal carcinomatosis are increasingly treated with curative intent and perioperative systemic chemotherapy combined with targeted therapy. The aim of this study was to analyze the potential impact of bevacizumab on early morbidity after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal carcinomatosis of colorectal origin.

Methods

From 2004 to 2010, in three referral centers, 182 patients with colorectal carcinomatosis were treated with complete cytoreduction followed by HIPEC after either preoperative systemic chemotherapy alone or in combination with bevacizumab. Because there was no control on treatment allocation, propensity score methods were used to control for this bias.

Results

The median time from discontinuation of bevacizumab to HIPEC was 7 weeks (range 6–10 weeks). Major morbidity was greater in the bevacizumab group (34 vs. 19 %, p = 0.020). Nine patients died postoperatively, 5 (6.2 %) in the bevacizumab group (n = 80) and 4 (3.9 %) in the group treated with chemotherapy alone (n = 102) (p = 0.130). The rate of digestive fistulas was greater in the bevacizumab group, although not statistically significant (18 vs. 10 %, p = 0.300). The effect of bevacizumab on major morbidity (including death) was found to be statistically significant (odds ratio 2.28, 95 % confidence interval 1.05–4.95) (p = 0.04).

Conclusions

Administration of bevacizumab before surgery with complete cytoreduction followed by HIPEC for colorectal carcinomatosis is associated with twofold increased morbidity. The oncologic benefit of bevacizumab before HIPEC remains to be evaluated.
Literatur
1.
Zurück zum Zitat Glehen O, Mohamed F, Gilly FN. Peritoneal carcinomatosis from digestive tract cancer: new management by cytoreductive surgery and intraperitoneal chemohyperthermia. Lancet Oncol. 2004;5:219–28. Glehen O, Mohamed F, Gilly FN. Peritoneal carcinomatosis from digestive tract cancer: new management by cytoreductive surgery and intraperitoneal chemohyperthermia. Lancet Oncol. 2004;5:219–28.
2.
Zurück zum Zitat Verwaal VJ, van Ruth S, de Bree E, van Sloothen GW, van Tinteren H, Boot H, et al. Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol. 2003;21:3737–43. Verwaal VJ, van Ruth S, de Bree E, van Sloothen GW, van Tinteren H, Boot H, et al. Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol. 2003;21:3737–43.
3.
Zurück zum Zitat Franko J, Shi Q, Goldman CD, Pockaj BA, Nelson GD, Goldberg RM, et al. Treatment of colorectal peritoneal carcinomatosis with systemic chemotherapy: a pooled analysis of north central cancer treatment group phase III trials N9741 and N9841. J Clin Oncol. 2012 20;30:263–7. Franko J, Shi Q, Goldman CD, Pockaj BA, Nelson GD, Goldberg RM, et al. Treatment of colorectal peritoneal carcinomatosis with systemic chemotherapy: a pooled analysis of north central cancer treatment group phase III trials N9741 and N9841. J Clin Oncol. 2012 20;30:263–7.
4.
Zurück zum Zitat Cao C, Yan TD, Black D, Morris DL. A systematic review and meta-analysis of cytoreductive surgery with perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis of colorectal origin. Ann Surg Oncol. 2009;16:2152–65. Cao C, Yan TD, Black D, Morris DL. A systematic review and meta-analysis of cytoreductive surgery with perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis of colorectal origin. Ann Surg Oncol. 2009;16:2152–65.
5.
Zurück zum Zitat Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6,336 patients and results of a survey. Ann Surg. 2004;240:205–13. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6,336 patients and results of a survey. Ann Surg. 2004;240:205–13.
6.
Zurück zum Zitat Fagotti A, Paris I, Grimolizzi F, Fanfani F, Vizzielli G, Naldini A, et al. Secondary cytoreduction plus oxaliplatin-based HIPEC in platinum-sensitive recurrent ovarian cancer patients: a pilot study. Gynecol Oncol. 2009;113:335–40. Fagotti A, Paris I, Grimolizzi F, Fanfani F, Vizzielli G, Naldini A, et al. Secondary cytoreduction plus oxaliplatin-based HIPEC in platinum-sensitive recurrent ovarian cancer patients: a pilot study. Gynecol Oncol. 2009;113:335–40.
7.
Zurück zum Zitat Gusani NJ, Cho SW, Colovos C, Seo S, Franko J, Richard SD, et al. Aggressive surgical management of peritoneal carcinomatosis with low mortality in a high-volume tertiary cancer center. Ann Surg Oncol. 2008;15:754–63. Gusani NJ, Cho SW, Colovos C, Seo S, Franko J, Richard SD, et al. Aggressive surgical management of peritoneal carcinomatosis with low mortality in a high-volume tertiary cancer center. Ann Surg Oncol. 2008;15:754–63.
8.
Zurück zum Zitat Spiliotis J, Rogdakis A, Vaxevanidou A, Datsis A, Zacharis G, Christopoulou A. Morbidity and mortality of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal carcinomatosis. J BUON. 2009;14:259–64. Spiliotis J, Rogdakis A, Vaxevanidou A, Datsis A, Zacharis G, Christopoulou A. Morbidity and mortality of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal carcinomatosis. J BUON. 2009;14:259–64.
9.
Zurück zum Zitat Sugarbaker PH. Surgical responsibilities in the management of peritoneal carcinomatosis. J Surg Oncol. 2010;101:713–24. Sugarbaker PH. Surgical responsibilities in the management of peritoneal carcinomatosis. J Surg Oncol. 2010;101:713–24.
10.
Zurück zum Zitat Verwaal VJ, van Tinteren H, Ruth SV, Zoetmulder FA. Toxicity of cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy. J Surg Oncol. 2004;85:61–67. Verwaal VJ, van Tinteren H, Ruth SV, Zoetmulder FA. Toxicity of cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy. J Surg Oncol. 2004;85:61–67.
11.
Zurück zum Zitat Yan TD, Deraco M, Baratti D, Kusamura S, Elias D, Glehen O, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: multi-institutional experience. J Clin Oncol. 2009;27:6237–42. Yan TD, Deraco M, Baratti D, Kusamura S, Elias D, Glehen O, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: multi-institutional experience. J Clin Oncol. 2009;27:6237–42.
12.
Zurück zum Zitat Chua TC, Yan TD, Saxena A, Morris DL. Should the treatment of peritoneal carcinomatosis by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy still be regarded as a highly morbid procedure? A systematic review of morbidity and mortality. Ann Surg. 2009;249:900–7. Chua TC, Yan TD, Saxena A, Morris DL. Should the treatment of peritoneal carcinomatosis by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy still be regarded as a highly morbid procedure? A systematic review of morbidity and mortality. Ann Surg. 2009;249:900–7.
13.
Zurück zum Zitat Quenet F, Goere D, Mehta SS, Roca L, Dumont F, Hessissen M, et al. Results of two bi-institutional prospective studies using intraperitoneal oxaliplatin with or without irinotecan during HIPEC after cytoreductive surgery for colorectal carcinomatosis. Ann Surg. 2011;254:294–301. Quenet F, Goere D, Mehta SS, Roca L, Dumont F, Hessissen M, et al. Results of two bi-institutional prospective studies using intraperitoneal oxaliplatin with or without irinotecan during HIPEC after cytoreductive surgery for colorectal carcinomatosis. Ann Surg. 2011;254:294–301.
14.
Zurück zum Zitat Elias D, Lefevre JH, Chevalier J, Brouquet A, Marchal F, Classe JM, et al. Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. J Clin Oncol. 2009;27:681–85. Elias D, Lefevre JH, Chevalier J, Brouquet A, Marchal F, Classe JM, et al. Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. J Clin Oncol. 2009;27:681–85.
15.
Zurück zum Zitat Elias D, Pocard M, Sideris L, Edè C, Ducreux M, Boige V, et al. Preliminary results of intraperitoneal chemohyperthermia with oxaliplatin in peritoneal carcinomatosis of colorectal origin. Br J Surg. 2004;91:455–56. Elias D, Pocard M, Sideris L, Edè C, Ducreux M, Boige V, et al. Preliminary results of intraperitoneal chemohyperthermia with oxaliplatin in peritoneal carcinomatosis of colorectal origin. Br J Surg. 2004;91:455–56.
16.
Zurück zum Zitat Wong R, Cunningham D, Barbachano Y, Saffery C, Valle J, Hickish T, et al. A multicentre study of capecitabine, oxaliplatin plus bevacizumab as perioperative treatment of patients with poor-risk colorectal liver-only metastases not selected for upfront resection. Ann Oncol. 2011;22:2042–48. Wong R, Cunningham D, Barbachano Y, Saffery C, Valle J, Hickish T, et al. A multicentre study of capecitabine, oxaliplatin plus bevacizumab as perioperative treatment of patients with poor-risk colorectal liver-only metastases not selected for upfront resection. Ann Oncol. 2011;22:2042–48.
17.
Zurück zum Zitat Kabbinavar F, Hurwitz HI, Fehrenbacher L, Meropol NJ, Novotny WF, Lieberman G, et al. Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol. 2003;21:60–65. Kabbinavar F, Hurwitz HI, Fehrenbacher L, Meropol NJ, Novotny WF, Lieberman G, et al. Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol. 2003;21:60–65.
18.
Zurück zum Zitat Kabbinavar FF, Hambleton J, Mass RD, Hurwitz HI, Bergsland E, Sarkar S. Combined analysis of efficacy: the addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer. J Clin Oncol. 2005;23:3706–12. Kabbinavar FF, Hambleton J, Mass RD, Hurwitz HI, Bergsland E, Sarkar S. Combined analysis of efficacy: the addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer. J Clin Oncol. 2005;23:3706–12.
19.
Zurück zum Zitat Saltz LB, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol. 2008;26:2013–19. Saltz LB, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol. 2008;26:2013–19.
20.
Zurück zum Zitat Hapani S, Chu D, Wu S. Risk of gastrointestinal perforation in patients with cancer treated with bevacizumab: a meta-analysis. Lancet Oncol. 2009;10:559–68. Hapani S, Chu D, Wu S. Risk of gastrointestinal perforation in patients with cancer treated with bevacizumab: a meta-analysis. Lancet Oncol. 2009;10:559–68.
21.
Zurück zum Zitat Meyerhardt JA, Li L, Sanoff HK, Carpenter Wt, Schrag D. Effectiveness of bevacizumab with first-line combination chemotherapy for Medicare patients with stage IV colorectal cancer. J Clin Oncol. 2012;30:608–15. Meyerhardt JA, Li L, Sanoff HK, Carpenter Wt, Schrag D. Effectiveness of bevacizumab with first-line combination chemotherapy for Medicare patients with stage IV colorectal cancer. J Clin Oncol. 2012;30:608–15.
22.
Zurück zum Zitat Kesmodel SB, Ellis LM, Lin E, Chang GJ, Abdalla EK, Kopetz S, et al. Preoperative bevacizumab does not significantly increase postoperative complication rates in patients undergoing hepatic surgery for colorectal cancer liver metastases. J Clin Oncol. 2008;26:5254–60. Kesmodel SB, Ellis LM, Lin E, Chang GJ, Abdalla EK, Kopetz S, et al. Preoperative bevacizumab does not significantly increase postoperative complication rates in patients undergoing hepatic surgery for colorectal cancer liver metastases. J Clin Oncol. 2008;26:5254–60.
23.
Zurück zum Zitat Chua TC, Morris DL, Saxena A, Esquivel J, Liauw W, Doerfer J, et al. Influence of modern systemic therapies as adjunct to cytoreduction and perioperative intraperitoneal chemotherapy for patients with colorectal peritoneal carcinomatosis: a multicenter study. Ann Surg Oncol. 2011;18:1560–67. Chua TC, Morris DL, Saxena A, Esquivel J, Liauw W, Doerfer J, et al. Influence of modern systemic therapies as adjunct to cytoreduction and perioperative intraperitoneal chemotherapy for patients with colorectal peritoneal carcinomatosis: a multicenter study. Ann Surg Oncol. 2011;18:1560–67.
24.
Zurück zum Zitat Scappaticci FA, Fehrenbacher L, Cartwright T, Hainsworth JD, Heim W, Berlin J, et al. Surgical wound healing complications in metastatic colorectal cancer patients treated with bevacizumab. J Surg Oncol. 2005;91:173–80. Scappaticci FA, Fehrenbacher L, Cartwright T, Hainsworth JD, Heim W, Berlin J, et al. Surgical wound healing complications in metastatic colorectal cancer patients treated with bevacizumab. J Surg Oncol. 2005;91:173–80.
25.
Zurück zum Zitat Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5:649–55. Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5:649–55.
26.
Zurück zum Zitat Sugarbaker PH. Intraperitoneal chemotherapy and cytoreductive surgery for the prevention and treatment of peritoneal carcinomatosis and sarcomatosis. Semin Surg Oncol. 1998;14:254–261. Sugarbaker PH. Intraperitoneal chemotherapy and cytoreductive surgery for the prevention and treatment of peritoneal carcinomatosis and sarcomatosis. Semin Surg Oncol. 1998;14:254–261.
27.
Zurück zum Zitat Sugarbaker PH. Peritonectomy procedures. Ann Surg. 1995;221:29–42. Sugarbaker PH. Peritonectomy procedures. Ann Surg. 1995;221:29–42.
28.
Zurück zum Zitat Jacquet P, Sugarbaker PH. Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis. Cancer Treat Res. 1996;82:359–74. Jacquet P, Sugarbaker PH. Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis. Cancer Treat Res. 1996;82:359–74.
29.
Zurück zum Zitat Martin RC 2nd, Brennan MF, Jaques DP. Quality of complication reporting in the surgical literature. Ann Surg. 2002;235:803–13. Martin RC 2nd, Brennan MF, Jaques DP. Quality of complication reporting in the surgical literature. Ann Surg. 2002;235:803–13.
30.
Zurück zum Zitat D’Agostino RB Jr. Propensity score methods for bias reduction in the comparison of a treatment to a nonrandomized control group. Stat Med. 1998;17:2265–81. D’Agostino RB Jr. Propensity score methods for bias reduction in the comparison of a treatment to a nonrandomized control group. Stat Med. 1998;17:2265–81.
31.
Zurück zum Zitat Rosenbaum RD. The central role of the propensity score in observational studies for causal effects. Biometrika. 1983;70:41–55. Rosenbaum RD. The central role of the propensity score in observational studies for causal effects. Biometrika. 1983;70:41–55.
32.
Zurück zum Zitat Gayat E, Pirracchio R, Resche-Rigon M, Mebazaa A, Mary JY, Porcher R. Propensity scores in intensive care and anaesthesiology literature: a systematic review. Intensive Care Med. 2010;36:1993–2003. Gayat E, Pirracchio R, Resche-Rigon M, Mebazaa A, Mary JY, Porcher R. Propensity scores in intensive care and anaesthesiology literature: a systematic review. Intensive Care Med. 2010;36:1993–2003.
33.
Zurück zum Zitat Austin PC. The performance of different propensity score methods for estimating marginal odds ratios. Stat Med. 2007;26:3078–94. Austin PC. The performance of different propensity score methods for estimating marginal odds ratios. Stat Med. 2007;26:3078–94.
34.
Zurück zum Zitat Austin PC. Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples. Stat Med. 2009;28:3083–3107. Austin PC. Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples. Stat Med. 2009;28:3083–3107.
35.
Zurück zum Zitat Glehen O, Kwiatkowski F, Sugarbaker PH, Elias D, Levine EA, De Simone M, et al. Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study. J Clin Oncol. 2004;22:3284–92. Glehen O, Kwiatkowski F, Sugarbaker PH, Elias D, Levine EA, De Simone M, et al. Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study. J Clin Oncol. 2004;22:3284–92.
36.
Zurück zum Zitat Elias D, Gilly F, Boutitie F, Quenet F, Bereder JM, Mansvelt B, et al. Peritoneal colorectal carcinomatosis treated with surgery and perioperative intraperitoneal chemotherapy: retrospective analysis of 523 patients from a multicentric French study. J Clin Oncol. 2010;28:63–68. Elias D, Gilly F, Boutitie F, Quenet F, Bereder JM, Mansvelt B, et al. Peritoneal colorectal carcinomatosis treated with surgery and perioperative intraperitoneal chemotherapy: retrospective analysis of 523 patients from a multicentric French study. J Clin Oncol. 2010;28:63–68.
Metadaten
Titel
Bevacizumab Doubles the Early Postoperative Complication Rate after Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Peritoneal Carcinomatosis of Colorectal Origin
verfasst von
Clarisse Eveno, MD, PhD
Guillaume Passot, MD
Diane Goéré, MD, PhD
Philippe Soyer, MD, PhD
Etienne Gayat, MD, PhD
Olivier Glehen, MD, PhD
Dominique Elias, MD, PhD
Marc Pocard, MD, PhD
Publikationsdatum
01.06.2014
Verlag
Springer US
Erschienen in
Annals of Surgical Oncology / Ausgabe 6/2014
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-013-3442-3

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