Skip to main content

Advertisement

Log in

The contribution of catumaxomab in the treatment of malignant ascites in patients with ovarian cancer: a review of the literature

  • Gynecologic Oncology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

The approval of the first specific drug catumaxomab for the treatment of malignant ascites is the subject of this review. This trifunctional antibody is known to kill EpCAM-positive tumor cells and therefore attacks the primary cause of malignant ascites formation in the peritoneal cavity. Until today catumaxomab is the only EpCam-targeted antibody approved by the European Medicines Agency. Ovarian cancer is caused by epithelial tumors cells which overexpress epithelial cell adhesion molecule (EpCAM). The existing literature concerning the use of catumaxomab for the treatment of malignant ascites associated with ovarian cancer until today is reported in this article. It is very encouraging that different prospective studies from diverse scientific teams recently presented positive results concerning the efficacy and the safety of catumaxomab in the treatment of malignant ascites in patients with ovarian cancer. A case of a patient with ovarian cancer FIGO IIIc is also referred in this article. A complete remission and stable disease was found after 4 i.p. infusions of catumaxomab.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Bookman MA (2009) Trials with impact on clinical management: first line. Int J Gynecol Cancer 19(Suppl 2):S55–S62 (review)

    Article  PubMed  Google Scholar 

  2. Ozols RF, Bundy BN, Greer BE, Fowler JM, Clarke-Pearson D, Burger RA, Mannel RS, DeGeest K, Hartenbach EM, Baergen R, Gynecologic Oncology Group (2003) Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol 21(17):3194–3200

    Article  PubMed  CAS  Google Scholar 

  3. Monk BJ, Choi DC, Pugmire G, Burger RA (2005) Activity of bevacizumab (rhuMAB VEGF) in advanced refractory epithelial ovarian cancer. Gynecol Oncol 96(3):902–905

    Article  PubMed  Google Scholar 

  4. Cannistra SA (2010) Evaluating new regimens in recurrent ovarian cancer: how much evidence is good enough? J Clin Oncol 28(19):3101–3103

    Article  PubMed  Google Scholar 

  5. Cannistra SA (2002) Is there a “best” choice of second-line agent in the treatment of recurrent, potentially platinum-sensitive ovarian cancer? J Clin Oncol 20(5):1158–1160

    PubMed  Google Scholar 

  6. Malayev Y, Levene R, Gonzalez F (2012) Palliative chemotherapy for malignant ascites secondary to ovarian cancer. Am J Hosp Palliat Care 29(7):515–521

    Article  PubMed  Google Scholar 

  7. Barni S, Cabiddu M, Ghilardi M, Petrelli F (2011) A novel perspective for an orphan problem: old and new drugs for the medical management of malignant ascites. Crit Rev Oncol Hematol 79(2):144–153. doi:10.1016/j.critrevonc.2010.07.016

  8. Shen-Gunther J, Mannel RS (2002) Ascites as a predictor of ovarian malignancy. Gynecol Oncol 87(1):77–83

    Article  PubMed  Google Scholar 

  9. Ayantunde AA, Parsons SL (2007) Pattern and prognostic factors in patients with malignant ascites: a retrospective study. Ann Oncol 18(5):945–949

    Article  PubMed  CAS  Google Scholar 

  10. Woopen H, Sehouli J (2009) Current and future options in the treatment of malignant ascites in ovarian cancer. Anticancer Res 29(8):3353–3359

    PubMed  Google Scholar 

  11. Smith EM, Jayson GC (2003) The current and future management of malignant ascites. Clin Oncol (R Coll Radiol) 15(2):59–72 (review)

    Article  CAS  Google Scholar 

  12. Xu L, Yoneda J, Herrera C, Wood J, Killion JJ, Fidler IJ (2000) Inhibition of malignant ascites and growth of human ovarian carcinoma by oral administration of a potent inhibitor of the vascular endothelial growth factor receptor tyrosine kinases. Int J Oncol 16(3):445–454

    PubMed  CAS  Google Scholar 

  13. Beattie GJ, Smyth JF (1998) Phase I study of intraperitoneal metalloproteinase inhibitor BB94 in patients with malignant ascites. Clin Cancer Res 4(8):1899–1902

    PubMed  CAS  Google Scholar 

  14. Kaufmann M, Schmid H, Raeth U, Grischke EM, Kempeni J, Schlick E, Bastert G (1990) Therapy of ascites with tumor necrosis factor in ovarian cancer. Geburtshilfe Frauenheilkd 50(9):678–682

    Article  PubMed  CAS  Google Scholar 

  15. Freedman RS, Kudelka AP, Kavanagh JJ, Verschraegen C, Edwards CL, Nash M, Levy L, Atkinson EN, Zhang HZ, Meelichar B, Patenia R, Templin S, Scott W, Platsoucas CD (2000) Clinical and biological effects of intraperitoneal injections of recombinant interferon-gamma and recombinant interleukin 2 with or without tumor-specific infiltrating lymphocytes in patients with ovarian or peritoneal carcinoma. Clin Cancer Res 6(6):2268–2278

    PubMed  CAS  Google Scholar 

  16. Walker J, Armstrong DK, Huang HQ, Fowler J, Webster K, Burger RA, Clarke Pearson D (2006) Intraperitoneal catheter outcomes in a phase 3 trial of intravenous versus intraperitoneal chemotherapy in an optimal stage 3 ovarian and primary peritoneal cancer: a Gynaecologic Oncology group study. Gynecol Oncol 100:27–32

    Article  PubMed  Google Scholar 

  17. Friedman RS, Deavers M, Liu J et al (2004) Peritoneal inflammation—a microenvironment for epithelial ovarian cancer (EOC). J Transl Med 2:23

    Article  Google Scholar 

  18. Revill Mely N, Bozzo J (2008) Catumaxomab anti-Ep-CAM monoclonal antibody. Drugs Future 33(5):385–391

    Article  Google Scholar 

  19. Linke R, Klein A, Seimetz D (2010) Catumaxomab: clinical development and future directions. MAbs 2(2):129–136

    Article  PubMed  Google Scholar 

  20. Zeidler R, Mysliwietz J, Csanady M et al (2000) The Fc-region of a new class of intact biospecific antibody mediates activation of accessory cells and NK Cells and induces phagocytosis tumor cells. Br J Cancer 83:261–266

    Article  PubMed  CAS  Google Scholar 

  21. Riesenberg R, Buchner A, Pohla H et al (2001) Lysis of prostate carcinoma cells by trifunctional bispecific antibodies (AEp-CAM X aCD3). J Histochem Cytochem 49:911–917

    Article  PubMed  CAS  Google Scholar 

  22. Schmitt M, Schmitt A, Reinhardt P, Thess B, Manfra B, Lindhofer H, Riechelmann H, Wiesneth M, Gronau S (2004) Opsonisation with a trifunctional bispecific (aCD3 × aEpCAM) antibody results in efficient lysis in vitro and in vivo of EpCAM-positive tumor cells by cytotoxic T lymphocytes. Int J Oncol 25(4):841–848

    PubMed  CAS  Google Scholar 

  23. Balzar M, Winter MJ, de Boer CJ, Litvinov SV (1999) The biology of the 17–1A antigen (Ep-CAM). J Mol Med (Berl). 77(10):699–712 (review)

    Article  PubMed  CAS  Google Scholar 

  24. Reichert JM, Valge-Archer VE (2007) Development trends for monoclonal antibody cancer therapeutics. Nat Rev Drug Discov 6(5):349–356 (review)

    Article  PubMed  CAS  Google Scholar 

  25. Heiss MM, Stroehlein MA, Jager M et al (2005) Immunotherapy of malignant ascites with trifunctional antibodies. Int J Cancer 117(3):435–443

    Article  PubMed  CAS  Google Scholar 

  26. Burges A, Wimberger P, Kümper C, Gorbounova V, Sommer H, Schmalfeldt B, Pfisterer J, Lichinitser M, Makhson A, Moiseyenko V, Lahr A, Schulze E, Jäger M, Ströhlein MA, Heiss MM, Gottwald T, Lindhofer H, Kimmig R (2007) Effective relief of malignant ascites in patients with advanced ovarian cancer by a trifunctional anti-EpCAM × anti-CD3 antibody: a phase I/II study. Clin Cancer Res 13(13):3899–3905

    Article  PubMed  CAS  Google Scholar 

  27. Heiss MM, Murawa P, Koralewski P, Kutarska E, Kolesnik OO, Ivanchenko VV, Dudnichenko AS, Aleknaviciene B, Razbadauskas A, Gore M, Ganea-Motan E, Ciuleanu T, Wimberger P, Schmittel A, Schmalfeldt B, Burges A, Bokemeyer C, Lindhofer H, Lahr A, Parsons SL (2010) The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: results of a prospective randomized phase II/III trial. Int J Cancer 127(9):2–2209

    Article  Google Scholar 

  28. Wimberger P, Gilet H, Gonschior A-K, Heiss MM, Moehler M, Oskay-Oezcelik G, Al-Batran S-E, Schmalfeldt B, Schmittel A, Schulze E, Parsons SL (2012) Deterioration in quality of life (QoL) in patients with malignant ascites: results from a phase II/III study comparing paracentesis plus catumaxomab with paracentesis alone. Ann Oncol 23(8):1979–1985

    Article  PubMed  CAS  Google Scholar 

  29. Removab® Summary of product characteristics, Sept. 2011. http://www.ema.europa.eu/

  30. Pietzner K, Chekerov R, Reinthaller A, Reimer D, Reimer T, Angleitner-Boubenizek L, Tschirschmann M, Lindhofer H, Braicu EI, Fotopoulou C, Sehouli J (2012) Matched pair analysis of intra- and postoperative catumaxomab in patients with ovarian cancer from a multicenter, single-arm phase II trial versus a consecutive single-center collective of ovarian cancer patients without immunotherapy. J Clin Oncol 30(Suppl; abstr 5080)

    Google Scholar 

  31. Papanikolaou G, Fotopoulou C, Braicu I, Chekerov R, Schmidt SC, Pietzner K, Sehouli J (2011) First surgical experience of intraperitoneal treatment with the trifunctional antibody catumaxomab (anti-EpCam × anti-CD3) for epithelial ovarian cancer. Anticancer Res 31(8):2603–2608

    PubMed  CAS  Google Scholar 

  32. Woopen H, Pietzner K, Darb-Esfahani S, Oskay-Oezcelik G, Sehouli J (2012) Extraperitoneal response to intraperitoneal immunotherapy with catumaxomab in a patient with cutaneous lymphangiosis carcinomatosa from ovarian cancer: a case report and review of the literature. Med Oncol 29(5):3416–3420

    Article  PubMed  CAS  Google Scholar 

  33. Petrelli F, Borgonovo K, Lonati V, Elia S, Barni S (2012) Regression of liver metastases after treatment with intraperitoneal catumaxomab for malignant ascites due to breast cancer. Targt Oncol [Epub ahead of print]

  34. Pietzner K, Jäger M, Schoberth A, Oskay-Özcelik G, Kuhberg M, Lindhofer H, Sehouli J (2012) First patient treated with a re-challenge of catumaxomab in recurrent malignant ascites: a case report. Med Oncol 29(2):1391–1396

    Article  PubMed  Google Scholar 

  35. Chekerov R, Reinthaller A, Reimer D, Reimer T, Angleitner-Boubenizek L, Halfen M, Lindhofer H, Braicu I, Oskay-özcelik G,Sehouli J (2010) Intraoperative immunotherapy with the trifunctional antibody catumaxomab in patients with ovarian cancer: results from a phase II study. American Society of Clinical Oncology, vol 28, no 15_suppl (May 20 Supplement), p 5039

  36. Ruf P, Kluge M, Jäger M, Burges A, Volovat C, Heiss MM, Hess J, Wimberger P, Brandt B, Lindhofer H (2010) Pharmacokinetics, immunogenicity and bioactivity of the therapeutic antibody catumaxomab intraperitoneally administered to cancer patients. Br J Clin Pharmacol 69(6):617–625

    Article  PubMed  CAS  Google Scholar 

  37. Ströhlein MA, Siegel R, Jäger M, Lindhofer H, Jauch KW, Heiss MM (2009) Induction of anti-tumor immunity by trifunctional antibodies in patients with peritoneal carcinomatosis. J Exp Clin Cancer Res 14(28):18

    Article  Google Scholar 

  38. Belau A, Pfisterer J, Wimpberger P, Kurzeder C, Du Bois A, Schouli J, Loibl S, Burchardi N (2007) Randomized, multicenter, two dose level open label phase II a study with the intraperitoneally infused trifunctional bispecific antibody catumaxomab to select the better dose level in platinum refractory epithelial ovarian cancer patients. J Clin Oncol 25(185) (June 20 Supplement 5556) (Part 1)

  39. Stroehlein MA, Lordick F, Ruettinger D, Gruetzner U, Menzel H, Bartelheim K, Jaeger M, Lindhofer H (2005) Treatment of peritoneal carcinomatosis due to GI tract cancer by intraperitoneal application of the trifunctional antibody catumaxomab: results of a phase I/II trial. J Clin Oncol 2005 ASCP Annual Meeting Proceedings, 23(165) (June 1 Supplement 2529) (Part I of II)

Download references

Conflict of interest

There is no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Panagiotis Tsikouras.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tsikouras, P., Tsagias, N., Pinidis, P. et al. The contribution of catumaxomab in the treatment of malignant ascites in patients with ovarian cancer: a review of the literature. Arch Gynecol Obstet 288, 581–585 (2013). https://doi.org/10.1007/s00404-013-2868-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-013-2868-y

Keywords

Navigation