Annals of Surgical Oncology

, Volume 21, Issue 9, pp 3023–3028 | Cite as

Neoadjuvant Chemotherapy with Bevacizumab May Improve Outcome after Cytoreduction and Hyperthermic Intraperitoneal Chemoperfusion (HIPEC) for Colorectal Carcinomatosis

  • Wim Ceelen
  • Yves Van Nieuwenhove
  • Dirk Vande Putte
  • Piet Pattyn
Gastrointestinal Oncology

Abstract

Background

In selected patients with colorectal peritoneal carcinomatosis (PC), cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) may improve survival. We aimed to assess whether neoadjuvant chemotherapy with or without bevacizumab is indicated in this patient population.

Methods

Colorectal PC patients were treated with CRS and HIPEC using oxaliplatin (200–460 mg/m2) or mitomycin C (35 mg/m2). Postoperative outcome and long-term survival were prospectively recorded. The impact of clinical variables on overall survival (OS) was assessed using univariate and Cox multivariate analysis.

Results

Between October 2002 and May 2012, 166 patients were treated with CRS and HIPEC. Neoadjuvant chemotherapy alone was administered to 21 % and neoadjuvant chemotherapy with bevacizumab to 16 % of patients. Postoperative mortality and major morbidity were 2.4 and 35 %, respectively. Half of the patients received adjuvant chemotherapy. After a median follow-up of 18 months, OS was 27 months (95 % confidence interval 20.8–33.2). On univariate analysis, OS was associated with extent of disease (P < 0.001), neoadjuvant chemotherapy with bevacizumab (P = 0.021), completeness of cytoreduction (CC) (P < 0.001), and adjuvant chemotherapy (P = 0.04), but not with primary disease site, synchronous presentation, or chemoperfusion drug. In multivariate Cox regression, independent predictors of OS were CC (hazard ratio 0.29, P < 0.001) and neoadjuvant therapy containing bevacizumab (hazard ratio 0.31, P = 0.019).

Conclusions

Long-term OS after CRS and HIPEC for colorectal cancer is associated with CC and neoadjuvant therapy containing bevacizumab. This regimen merits prospective study in patients with resectable PC of colorectal origin.

Keywords

Overall Survival Bevacizumab Oxaliplatin Peritoneal Carcinomatosis Colorectal Origin 

Notes

Acknowledgments

W.C. is a senior clinical investigator of the Fund for Scientific Research–Flanders (FWO). We thank Natacha Rosseel for administering the clinical database.

Disclosure

The authors declare no conflict of interest.

References

  1. 1.
    Herszényi L, Tulassay Z. Epidemiology of gastrointestinal and liver tumors. Eur Rev Med Pharmacol Sci. 2010;14:249–58.PubMedGoogle Scholar
  2. 2.
    Peeters M, Price T. Biologic therapies in the metastatic colorectal cancer treatment continuum—applying current evidence to clinical practice. Cancer Treat Rev. 2012;38:397–406.PubMedCrossRefGoogle Scholar
  3. 3.
    Klaver YLB, Simkens LHJ, Lemmens V, et al. Outcomes of colorectal cancer patients with peritoneal carcinomatosis treated with chemotherapy with and without targeted therapy. Eur J Surg Oncol. 2012;38:617–23.PubMedCrossRefGoogle Scholar
  4. 4.
    Sugarbaker PH, Ryan DP. Cytoreductive surgery plus hyperthermic perioperative chemotherapy to treat peritoneal metastases from colorectal cancer: standard of care or an experimental approach? Lancet Oncol. 2012;13:E362–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Verwaal VJ, van Ruth S, de Bree E, 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.PubMedCrossRefGoogle Scholar
  6. 6.
    Ceelen WP. Current management of peritoneal carcinomatosis from colorectal cancer. Minerva Chir. 2013;68:77–86.PubMedGoogle Scholar
  7. 7.
    Ceelen W, De Somer F, Van Nieuwenhove Y, Vande Putte D, Pattyn P. Effect of perfusion temperature on glucose and electrolyte transport during hyperthermic intraperitoneal chemoperfusion (HIPEC) with oxaliplatin. Eur J Surg Oncol. In press.Google Scholar
  8. 8.
    Ceelen WP, Peeters M, Houtmeyers P, Breusegem C, De Somer F, Pattyn P. Safety and efficacy of hyperthermic intraperitoneal chemoperfusion with high-dose oxaliplatin in patients with peritoneal carcinomatosis. Ann Surg Oncol. 2008;15:535–41.PubMedCrossRefGoogle Scholar
  9. 9.
    Lemmens VE, Klaver YL, Verwaal VJ, Rutten HJ, Coebergh JWW, de Hingh IH. Predictors and survival of synchronous peritoneal carcinomatosis of colorectal origin: a population-based study. Int J Cancer. 2011;128:2717–25.PubMedCrossRefGoogle Scholar
  10. 10.
    Konigsrainer I, Horvath P, Struller F, Forkl V, Konigsrainer A, Beckert S. Risk factors for recurrence following complete cytoreductive surgery and HIPEC in colorectal cancer–derived peritoneal surface malignancies. Langenbecks Arch Surg. 2013;398:745–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Elias D, Gilly F, Boutitie F, 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;28:63–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Glehen O, Kwiatkowski F, Sugarbaker PH, 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.PubMedCrossRefGoogle Scholar
  13. 13.
    Cavaliere F, De Simone M, Virzi S, et al. Prognostic factors and oncologic outcome in 146 patients with colorectal peritoneal carcinomatosis treated with cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy: Italian multicenter study S.I.T.I.L.O. Eur J Surg Oncol. 2011;37:148–54.PubMedCrossRefGoogle Scholar
  14. 14.
    Passot G, Vaudoyer D, Cotte E, et al. Progression following neoadjuvant systemic chemotherapy may not be a contraindication to a curative approach for colorectal carcinomatosis. Ann Surg. 2012;256:125–29.PubMedCrossRefGoogle Scholar
  15. 15.
    Klaver YLB, de Hingh I, Boot H, Verwaal VJ. Results of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy after early failure of adjuvant systemic chemotherapy. J Surg Oncol. 2011;103:431–4.PubMedCrossRefGoogle Scholar
  16. 16.
    Moghaddam SM, Amini A, Morris DL, Pourgholami MH. Significance of vascular endothelial growth factor in growth and peritoneal dissemination of ovarian cancer. Cancer Metastasis Rev. 2012;31:143–62.CrossRefGoogle Scholar
  17. 17.
    Retsky MW, Hrushesky WJM, Gukas ID. Hypothesis: primary antiangiogenic method proposed to treat early stage breast cancer. BMC Cancer. 2009;9.Google Scholar
  18. 18.
    Nasti G, Piccirillo MC, Izzo F, et al. Neoadjuvant FOLFIRI plus bevacizumab in patients with resectable liver metastases from colorectal cancer: a phase 2 trial. Br J Cancer. 2013;108:1566–70.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Eveno C, Passot G, Goere D, et al. Bevacizumab doubles the early postoperative complication rate after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis of colorectal origin. Ann Surg Oncol. In press.Google Scholar
  20. 20.
    Kesmodel SB, Ellis LM, Lin E, 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.PubMedCrossRefGoogle Scholar
  21. 21.
    Chereau E, Lambaudie E, Houvenaeghel G. Morbidity of surgery after neoadjuvant chemotherapy including bevacizumab for advanced ovarian cancer. Int J Gynecol Cancer. 2013;23:1326–30.PubMedCrossRefGoogle Scholar
  22. 22.
    van der Pool AE, Marsman HA, Verheij J, et al. Effect of bevacizumab added preoperatively to oxaliplatin on liver injury and complications after resection of colorectal liver metastases. J Surg Oncol. 2012;106:892–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Votanopoulos K, Ihemelandu C, Shen P, Stewart J, Russell G, Levine EA. A comparison of hematologic toxicity profiles after heated intraperitoneal chemotherapy with oxaliplatin and mitomycin C. J Surg Res. 2013;179: E133–39.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Glockzin G, von Breitenbuch P, Schlitt HJ, Piso P. Treatment-related morbidity and toxicity of CRS and oxaliplatin-based HIPEC compared to a mitomycin and doxorubicin-based HIPEC protocol in patients with peritoneal carcinomatosis: a matched-pair analysis. J Surg Oncol. 2013;107:574–8.PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2014

Authors and Affiliations

  • Wim Ceelen
    • 1
  • Yves Van Nieuwenhove
    • 1
  • Dirk Vande Putte
    • 1
  • Piet Pattyn
    • 1
  1. 1.Department of SurgeryGhent University HospitalGhentBelgium

Personalised recommendations