Annals of Surgical Oncology

, Volume 19, Issue 4, pp 1326–1333 | Cite as

Feasibility of Surgery After Systemic Treatment with the Humanized Recombinant Antibody Bevacizumab in Heavily Pretreated Patients with Advanced Epithelial Ovarian Cancer

  • Jalid Sehouli
  • G. Papanikolaou
  • E.-I. Braicu
  • K. Pietzner
  • P. Neuhaus
  • C. Fotopoulou
Gynecologic Oncology

Abstract

Background

The aim of this study was to assess operative feasibility and outcome after bevacizumab treatment (BT) in ovarian cancer (OC) patients.

Patients and Methods

We retrospectively identified all OC patients operated between April 2006 and September 2010 after BT.

Results

We identified 733 OC operations, 10 of which (1.36%) were performed in a mean time of 134 days (range, 10–288) after BT. Indication was secondary cytoreduction in 3 patients (mean days after BT, 181; range, 82–256) and palliation in 7 due to bowel obstruction and/or intestinal perforation or fistula (mean days after BT, 114; range, 10–288). All but 1 acutely operated patients developed a secondary wound healing, but none of the 3 patients after planned cytoreduction did. Of these 3 patients, 1 suddenly died on the 36th postoperative day, presumably of thromboembolism. None of the patients developed postoperatively a gastrointestinal morbidity; however, in 1 patient operated 21 days after BT due to a vesicointestinal fistula the bladder reconstruction could not heal and developed a permanent fistula.

Conclusions

Emergency surgery after BT due to bowel obstruction and/or fistulas seems to be associated with an impaired wound healing in advanced heavily pretreated platinum-resistant OC patients, while this does not appear the case in planned cytoreduction. Prospective evaluations are warranted to assess surgical safety after BT in this special patients’ collective.

Keywords

Bevacizumab Ovarian Cancer Patient Short Bowel Syndrome Recurrent Ovarian Cancer Bevacizumab Treatment 

References

  1. 1.
    Teoh DG, Secord AA. Antiangiogenic therapies in epithelial ovarian cancer. Cancer Control. 2011;18:31–43.PubMedGoogle Scholar
  2. 2.
    Eskens FA, Sleijfer S. The use of bevacizumab in colorectal, lung, breast, renal and ovarian cancer: where does it fit? Eur J Cancer. 2008;44:2350–6.PubMedCrossRefGoogle Scholar
  3. 3.
    Burger RA. Experience with bevacizumab in the management of epithelial ovarian cancer. J Clin Oncol. 2007;25:2902–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Burger RA. Overview of anti-angiogenic agents in development for ovarian cancer. Gynecol Oncol. 2011;121:230–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Koskas M, Chereau E, Ballester M, Selle F, Rouzier R, Daraï E. Wound complications after bevacizumab treatment in patients operated on for ovarian cancer. Anticancer Res. 2010;30:4743–7.PubMedGoogle Scholar
  6. 6.
    Sfakianos GP, Numnum TM, Halverson CB, Panjeti D, Kendrick JE 4th, Straughn JM Jr. The risk of gastrointestinal perforation and/or fistula in patients with recurrent ovarian cancer receiving bevacizumab compared to standard chemotherapy: a retrospective cohort study. Gynecol Oncol. 2009;114:424–6.PubMedCrossRefGoogle Scholar
  7. 7.
    Chéreau E, Stefanescu D, Selle F, Rouzier R, Daraï E. Spontaneous rectovaginal fistula during bevacizumab therapy for ovarian cancer: a case report. Am J Obstet Gynecol. 2009;200:e15–6.PubMedCrossRefGoogle Scholar
  8. 8.
    Randall LM, Monk BJ. Bevacizumab toxicities and their management in ovarian cancer. Gynecol Oncol. 2010;117:497–504.PubMedCrossRefGoogle Scholar
  9. 9.
    Bansal N, Hoffman M. Bladder perforation in a patient with recurrent epithelial ovarian cancer after treatment with bevacizumab. Gynecol Oncol. 2011;120:313–4.PubMedCrossRefGoogle Scholar
  10. 10.
    Monk BJ, Han E, Josephs-Cowan CA, Pugmire G, Burger RA. Salvage bevacizumab (rhuMAB VEGF)-based therapy after multiple prior cytotoxic regimens in advanced refractory epithelial ovarian cancer. Gynecol Oncol. 2006;102:140–4.PubMedCrossRefGoogle Scholar
  11. 11.
    S. Janczar, JS Graham, AJW Paige, H Gabra. Targeting locoregional peritoneal dissemination in ovarian cancer. Expert Rev Obstet. Gynecol. 2009;4:133–47.CrossRefGoogle Scholar
  12. 12.
    Gruenberger B, Tamandl D, Schueller J, Scheithauer W, Zielinski C, Herbst F, et al. Bevacizumab, capecitabine, and oxaliplatin as neoadjuvant therapy for patients with potentially curable metastatic colorectal cancer. J Clin Oncol. 2008;26:1830–5.PubMedCrossRefGoogle Scholar
  13. 13.
    Reddy SK, Morse MA, Hurwitz HI, Bendell JC, Gan TJ, Hill SE, et al. 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. 2008;206:96–106.PubMedCrossRefGoogle Scholar
  14. 14.
    Kristensen G, Perren T, Qian W, Pfisterer J, Ledermann JA, Joly F, et al. Result of interim analysis of overall survival in the GCIG ICON7 phase III randomized trial of bevacizumab in women with newly diagnosed ovarian cancer. J Clin Oncol. 2011;29:LBA5006.Google Scholar
  15. 15.
    Harter P, Hahmann M, Lueck HJ, Poelcher M, Wimberger P, Ortmann O, et al. Surgery for recurrent ovarian cancer: role of peritoneal carcinomatosis: exploratory analysis of the DESKTOP I Trial about risk factors, surgical implications, and prognostic value of peritoneal carcinomatosis. Ann Surg Oncol. 2009;16:1324–30.PubMedCrossRefGoogle Scholar
  16. 16.
    Sehouli J, Senyuva F, Fotopoulou C, Neumann U, Denkert C, Werner L, et al. Intra-abdominal tumor dissemination pattern and surgical outcome in 214 patients with primary ovarian cancer. J Surg Oncol. 2009;99:424–7.PubMedCrossRefGoogle Scholar
  17. 17.
    Sehouli J, Könsgen D, Mustea A, Oskay-Ozcelik G, Katsares I, Weidemann H, et al. “IMO”- intraoperative mapping of ovarian cancer. Zentralbl Gynakol. 2003;125:129–35.PubMedCrossRefGoogle Scholar
  18. 18.
    Adhesion Scoring Group, Improvement of interobserver reproducibility of adhesion scoring systems. Fertil Steril. 1994;62:984–8.Google Scholar
  19. 19.
    Cohen Z, Senagore AJ, Dayton MT, Koruda MJ, Beck DE, Wolff BG, et al. Prevention of postoperative abdominal adhesions by a novel, glycerol/sodium hyaluronate/carboxymethylcellulose–based bioresorbable membrane: a prospective, randomized, evaluator-blinded multicenter study. Dis Colon Rectum. 2005;48:1130–9.PubMedCrossRefGoogle Scholar
  20. 20.
    International Federation of Gynecology and Obstetrics. Changes in definitions of clinical staging for carcinoma of the cervix and ovary. Am J Obstet Gynecol. 1987:156:263–4.Google Scholar
  21. 21.
    Pietzner K, Schmuck RB, Fotopoulou C, Gellermann J, Ismaeel F, Cho CH, et al. Long term combination treatment with bevacizumab, pegylated liposomal Doxorubicin and regional abdominal hyperthermia in platinum refractory ovarian cancer: a case report and review of the literature. Anticancer Res. 2011;31:2675–7.PubMedGoogle Scholar
  22. 22.
    August DA, Serrano D, Poplin E. “Spontaneous” delayed colon and rectal anastomotic complications associated with Bevacizumab therapy. J Surg Oncol. 2008;97:180–5.PubMedCrossRefGoogle Scholar
  23. 23.
    Wolf I, Urban D, Pfeffer R, Catane R, Aderka D. High incidence of fistula formation during bevacizumab treatment in rectal cancer patients. Acta Oncol. 2007;46:550–3.PubMedCrossRefGoogle Scholar
  24. 24.
    Adenis A, Vanseymortier L, Foissey D, Colombel JF. Bevacizumab and postponed suture leakages after surgery for ulceration cancer. Gut. 2007;56:734.PubMedCrossRefGoogle Scholar
  25. 25.
    Ley EJ, Vukasin P, Kaiser AM, Ault G, Beart RW. Delayed rectovaginal fistula: a potential complication of bevacizumab (Avastin). Dis Colon Rectum. 2007;50:930.PubMedCrossRefGoogle Scholar
  26. 26.
    Han ES, Monk BJ. What is the risk of bowel perforation associated with bevacizumab therapy in ovarian cancer? Gynecol Oncol. 2007;105:3–6.PubMedCrossRefGoogle Scholar
  27. 27.
    Diaz JP, Tew WP, Zivanovic O, Konner J, Sabbatini PJ, dos Santos LA, et al. Incidence and management of bevacizumab-associated gastrointestinal perforations in patients with recurrent ovarian carcinoma. Gynecol Oncol. 2010;116:335–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Sánchez-Muñoz A, Mendiola C, Pérez-Ruiz E, Rodríguez-Sánchez CA, Jurado JM, Alonso-Carrión L, et al. Bevacizumab plus low-dose metronomic oral cyclophosphamide in heavily pretreated patients with recurrent ovarian cancer. Oncology. 2010;79:98–104.PubMedCrossRefGoogle Scholar
  29. 29.
    Chura JC, Van Iseghem K, Downs LS Jr, Carson LF, Judson PL. Bevacizumab plus cyclophosphamide in heavily pretreated patients with recurrent ovarian cancer. Gynecol Oncol. 2007;107:326–30.PubMedCrossRefGoogle Scholar
  30. 30.
    Badgwell BD, Camp ER, Feig B, Wolff RA, Eng C, Ellis LM, et al. Management of bevacizumab-associated bowel perforation: a case series and review of the literature. Ann Oncol. 2008;19:577–82.PubMedCrossRefGoogle Scholar
  31. 31.
    Khasraw M, Holodny A, Goldlust SA, Deangelis LM. Intracranial hemorrhage in patients with cancer treated with bevacizumab: the Memorial Sloan-Kettering experience. Ann Oncol. 2011 May 4 [Epub ahead of print].Google Scholar
  32. 32.
    Burkart CM, Grisel JJ, Hom DB. Spontaneous nasal septal perforation with antiangiogenic bevacizumab therapy. Laryngoscope. 2008;118:1539–41.PubMedCrossRefGoogle Scholar
  33. 33.
    Richardson DL, Backes FJ, Hurt JD, Seamon LG, Copeland LJ, Fowler JM, et al. Which factors predict bowel complications in patients with recurrent epithelial ovarian cancer being treated with bevacizumab? Gynecol Oncol. 2010;118:47–51.PubMedCrossRefGoogle Scholar
  34. 34.
    Tanyi JL, McCann G, Hagemann AR, Coukos G, Rubin SC, Liao JB, et al. Clinical predictors of bevacizumab-associated gastrointestinal perforation. Gynecol Oncol. 2011;120:464–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Simpkins F, Belinson JL, Rose PG. Avoiding bevacizumab related gastrointestinal toxicity for recurrent ovarian cancer by careful patient screening. Gynecol Oncol. 2007;107:118–23.PubMedCrossRefGoogle Scholar
  36. 36.
    Basbug M, Bulbuller N, Camci C, Ayten R, Aygen E, Ozercan IH, et al. The effect of antivascular endothelial growth factor on the development of adhesion formation in laparotomized rats: experimental study. Gastroenterol Res Pract. 2011;2011:578691 [Epub June 28 2011].Google Scholar
  37. 37.
    Kudoh K, Takano M, Kouta H, Kikuchi R, Kita T, Miyamoto M, et al. Effects of bevacizumab and pegylated liposomal doxorubicin for the patients with recurrent or refractory ovarian cancers. Gynecol Oncol. 2011;122:233–7.PubMedCrossRefGoogle Scholar
  38. 38.
    O’Malley DM, Richardson DL, Rheaume PS, Salani R, Eisenhauer EL, McCann GA, et al. Addition of bevacizumab to weekly paclitaxel significantly improves progression-free survival in heavily pretreated recurrent epithelial ovarian cancer. Gynecol Oncol. 2011;121:269–72.PubMedCrossRefGoogle Scholar
  39. 39.
    Guarneri V, Piacentini F, Barbieri E, Conte PF. Achievements and unmet needs in the management of advanced ovarian cancer. Gynecol Oncol. 2010;117:152–8.PubMedCrossRefGoogle Scholar
  40. 40.
    Penson RT, Dizon DS, Cannistra SA, Roche MR, Krasner CN, Berlin ST, et al. Phase II study of carboplatin, paclitaxel, and bevacizumab with maintenance bevacizumab as first-line chemotherapy for advanced mullerian tumors. J Clin Oncol. 2010;28:154–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Hurt JD, Richardson DL, Seamon LG, Fowler JF, Copeland LJ, Cohn DE, et al. Sustained progression-free survival with weekly paclitaxel and bevacizumab in recurrent ovarian cancer. Gynecol Oncol. 2009;115:396–400.PubMedCrossRefGoogle Scholar
  42. 42.
    Cannistra SA, Matulonis UA, Penson RT, Hambleton J, Dupont J, Mackey H, et al. Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol. 2007;25:5180–6. Erratum in: J Clin Oncol. 2008;26:1773.Google Scholar
  43. 43.
    Burger RA, Sill MW, Monk BJ, Greer BE, Sorosky JI. Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2007;25:5165–71.PubMedCrossRefGoogle Scholar
  44. 44.
    Cohn DE, Valmadre S, Resnick KE, Eaton LA, Copeland LJ, Fowler JM. Bevacizumab and weekly taxane chemotherapy demonstrates activity in refractory ovarian cancer. Gynecol Oncol. 2006;102:134–9.PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2011

Authors and Affiliations

  • Jalid Sehouli
    • 1
  • G. Papanikolaou
    • 1
  • E.-I. Braicu
    • 1
  • K. Pietzner
    • 1
  • P. Neuhaus
    • 2
  • C. Fotopoulou
    • 1
  1. 1.Department of Gynecology, European Competence Centre for Ovarian CancerCharité-University HospitalBerlinGermany
  2. 2.Department of General, Visceral, and Transplantation SurgeryHumboldt UniversityVirchow KlinikumGermany

Personalised recommendations