Annals of Surgical Oncology

, Volume 21, Issue 6, pp 1792–1800 | Cite as

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

  • Clarisse Eveno
  • Guillaume Passot
  • Diane Goéré
  • Philippe Soyer
  • Etienne Gayat
  • Olivier Glehen
  • Dominique Elias
  • Marc Pocard
Colorectal Cancer

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.

Keywords

Bevacizumab Propensity Score Oxaliplatin Peritoneal Carcinomatosis Intraperitoneal Chemotherapy 

Notes

Conflict of interest

The authors declare no conflict of interest.

References

  1. 1.
    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.Google Scholar
  2. 2.
    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.Google Scholar
  3. 3.
    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.Google Scholar
  4. 4.
    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.Google Scholar
  5. 5.
    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.Google Scholar
  6. 6.
    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.Google Scholar
  7. 7.
    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.Google Scholar
  8. 8.
    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.Google Scholar
  9. 9.
    Sugarbaker PH. Surgical responsibilities in the management of peritoneal carcinomatosis. J Surg Oncol. 2010;101:713–24.Google Scholar
  10. 10.
    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.Google Scholar
  11. 11.
    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.Google Scholar
  12. 12.
    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.Google Scholar
  13. 13.
    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.Google Scholar
  14. 14.
    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.Google Scholar
  15. 15.
    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.Google Scholar
  16. 16.
    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.Google Scholar
  17. 17.
    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.Google Scholar
  18. 18.
    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.Google Scholar
  19. 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.Google Scholar
  20. 20.
    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.Google Scholar
  21. 21.
    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.Google Scholar
  22. 22.
    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.Google Scholar
  23. 23.
    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.Google Scholar
  24. 24.
    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.Google Scholar
  25. 25.
    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.Google Scholar
  26. 26.
    Sugarbaker PH. Intraperitoneal chemotherapy and cytoreductive surgery for the prevention and treatment of peritoneal carcinomatosis and sarcomatosis. Semin Surg Oncol. 1998;14:254–261.Google Scholar
  27. 27.
    Sugarbaker PH. Peritonectomy procedures. Ann Surg. 1995;221:29–42.Google Scholar
  28. 28.
    Jacquet P, Sugarbaker PH. Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis. Cancer Treat Res. 1996;82:359–74.Google Scholar
  29. 29.
    Martin RC 2nd, Brennan MF, Jaques DP. Quality of complication reporting in the surgical literature. Ann Surg. 2002;235:803–13.Google Scholar
  30. 30.
    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.Google Scholar
  31. 31.
    Rosenbaum RD. The central role of the propensity score in observational studies for causal effects. Biometrika. 1983;70:41–55.Google Scholar
  32. 32.
    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.Google Scholar
  33. 33.
    Austin PC. The performance of different propensity score methods for estimating marginal odds ratios. Stat Med. 2007;26:3078–94.Google Scholar
  34. 34.
    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.Google Scholar
  35. 35.
    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.Google Scholar
  36. 36.
    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.Google Scholar

Copyright information

© Society of Surgical Oncology 2013

Authors and Affiliations

  • Clarisse Eveno
    • 1
    • 2
  • Guillaume Passot
    • 3
    • 4
  • Diane Goéré
    • 5
  • Philippe Soyer
    • 6
  • Etienne Gayat
    • 7
    • 8
  • Olivier Glehen
    • 3
    • 4
  • Dominique Elias
    • 5
  • Marc Pocard
    • 1
    • 2
  1. 1.Department of Digestive DiseaseHôpital Lariboisière-AP-HP & Université Diderot-Paris 7ParisFrance
  2. 2.UMR INSERM 965-Paris 7 “Angiogenèse et recherche translationnelle”Hôpital Lariboisière-AP-HPParisFrance
  3. 3.Department of Digestive SurgeryCentre Hospitalier Lyon Sud, Université LyonPierre BéniteFrance
  4. 4.Department of Digestive SurgeryUniversité LyonLyonFrance
  5. 5.Department of Surgical OncologyInstitut Gustave RoussyVillejuif CedexFrance
  6. 6.Department of Abdominal & Interventional ImagingHôpital Lariboisière-AP-HP & Université Diderot-Paris 7ParisFrance
  7. 7.Department of Intensive CareHôpital Lariboisière-AP-HP & Université Diderot-Paris 7ParisFrance
  8. 8.Department of Biostatistics and Clinical EpidemiologyHôpital Saint-Louis-AP-HP & Université Diderot-Paris 7ParisFrance

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