Intraperitoneal Therapy of Ovarian Cancer with Radiolabeled Monoclonal Antibodies

  • Haralambos Kalofonos
  • Agamemnon A. Epenetos
Conference paper
Part of the NATO ASI Series book series (NSSA, volume 152)


Intravenously administered radiolabeled tumor associated monoclonal antibodies can achieve successful imaging of tumor masses. However, the absolute amount of radiolabel reaching the tumor is disappointingly small and cannot, at present, be used therapeutically for most epithelial origin cancers although some encouraging exceptions have been reported.

One manoeuvre that has met with some apparent success is that of intracavity administration of labeled antibodies. The rationale here is that if intravenous administration of the antibodies leads to too small an uptake due to dilution, dissociation and catabolism, then direct placing of the antibody into a body region may enhance its chances of reaching the target. This form of therapy has been applied to the peritoneum for the treatment of ovarian cancer and to the pleural and pericardial cavities for the treatment of malignant serous effusions. Pharmacokinetic studies have shown that there is an exploitable concentration difference between the peritoneum and the plasma for many anti-neoplastic agents and furthermore, that macromolecules such as antibodies can penetrate deeper into tissues than conventional chemotherapy agents of smaller molecular weight. Using an experimental model (nude mice with intraperitoneally implanted human xenograft), it was shown that we could achieve a fifty-fold increase and faster localization of intraperitoneally administered antibody as compared to intravenous administration.

A Phase I clinical trial of intraperitoneally administered I-131 labeled tumor associated monoclonal antibodies was conducted in 12 patients with advanced ovarian cancer resistant to chemotherapy and/or abdominal radiotherapy. Toxicity was noted at a level of 100 mCi in patients with malignant ascites, and 150 mCi in patients without ascites. Diarrhoea and cytopenia were more marked in patients who had previously received abdominal radiotherapy. Three out of four patients with Stage IV and large volume disease (> 2 cm diameter) benefited symptomatically but died of their disease three to six months after treatment. Two patients with Stage III and large volume disease (> 2 cm diameter) had stable disease at six and eight months after treatment. Four out of six patients with Stage III and small volume (< 2 cm diameter) achieved complete remission for 3-24 months after treatment. Two out of these patients had positive washings as the only evidence of disease and they remain in remission for more than two years after therapy.

A Phase II double blind randomized clinical trial has recently commenced to examine these effects on a large number of patients and to define the mode of action of this method.


Ovarian Cancer Minimal Residual Disease Advanced Ovarian Cancer Malignant Ascites Abdominal Radiotherapy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    G. Kohler and C. Milstein, Continuous cultures of fused cells secreting antibodies of predefined specificity, Nature 256:495–497 (1975).PubMedCrossRefGoogle Scholar
  2. 2.
    R. W. Baldwin and M. V. Pimm, Antitumor monoclonal antibodies for radioimmunodetection of tumors and drug targeting, Cancer Metastasis Rev. 2(1):89–106 (1983).PubMedCrossRefGoogle Scholar
  3. 3.
    R. E. Thorpe and W. C. Ross, The preparation and cytotoxic properties of antibody-toxin conjugates, Immun. Rev. 62:119 (1982).PubMedCrossRefGoogle Scholar
  4. 4.
    S. E. Order, J. L. Klein, D. Ettinger, et al., Use of isotopic immunoglobulin in therapy, Cancer Res. 40:3001 (1980).PubMedGoogle Scholar
  5. 5.
    A. A. Epenetos et al., Antibody guided irradiation of malignant lesions, Lancet 30:1441–1443 (1984).Google Scholar
  6. 6.
    J. A. Carrasquillo, K. A. Krohn, P. Beaumiere, et al., Diagnosis of and therapy for solid tumors with radiolabeled antibodies and immune fragments, Cancer Treat. Rep. 68:371–378 (1984).Google Scholar
  7. 7.
    R. S. Benua, N. R. Cicale, et al., The relation of radioiodine dosimetry to results and complications in the treatment of metastatic thyroid cancer, Am. J. Roentgenol. 87:171–182 (1962).Google Scholar
  8. 8.
    E. L. Mazzaferri and R. L. Young, Papillary thyroid carcinoma: a 10 year follow-up report of the impact of therapy in 576 patients, Am. J. Med. 70:511–518 (1981).PubMedCrossRefGoogle Scholar
  9. 9.
    A. A. Epenetos, Monoclonal antibodies for the localization of human neoplasms in vitro and in vivo, PhD Thesis, University of London, pp 183–197 (1983).Google Scholar
  10. 10.
    S. E. Order, The history and progress of serologic immunotherapy and radiodiagnosis, Radiology 118:219–223 (1976).PubMedGoogle Scholar
  11. 11.
    D. S. Ettinger, S. E. Order, M. D. Wharam et al., Phase I–II of isotopic immunoglobulin therapy for primary liver cancer, Cancer Treat. Rep. 66:289–97 (1982).PubMedGoogle Scholar
  12. 12.
    A. A. Epenetos, N. Courtenay-Luck, D. Pickering, et al., Antibody guided irradiation of brain glioma by arterial infusion of radioactive monoclonal antibody against epidermal growth factor receptor and blood group A antigen, Br. Med. J. 290:1463–1466 (1985).CrossRefGoogle Scholar
  13. 13.
    T. Fukumoto and M. R. Brandon, The site of IgG1a catabolism in the rat, Molec. Immunol. 18:741–750 (1981).CrossRefGoogle Scholar
  14. 14.
    G. Rowlinson, D. Snook, and A. A. Epenetos, Antibody guided localization of intraperitoneal tumors following i.p. or i.v. antibody administration, Br. J. Cancer (in press).Google Scholar
  15. 15.
    E. Boye, M. W. Lindegaard, E. Pans, et al., Whole body distribution of radioactivity after intraperitoneal administration of P-32 colloids, Br. J. Radiol. 57:395–402 (1984).PubMedCrossRefGoogle Scholar
  16. 16.
    R. A. Miller, D. G. Malloney, R. Warnke, et al., Treatment of B-cell lymphoma with monoclonal anti-idiotype antibody, New Eng. J. Med. 306:517–522 (1982).PubMedCrossRefGoogle Scholar
  17. 17.
    C. M. Haskell, Cancer of the Ovary, in: “Cancer Treatment,” (2nd Ed), W. B. Saunders Company, pp. 409–429 (1985).Google Scholar
  18. 18.
    J. Taylor-Papadimitriou, J. Peterson, J. Arklie, et al., Monoclonal antibody to epithelium-specific components of the human milk fat globule membrane. Production and reaction with cells in culture., Int. J. Cancer 28:17–21 (1981).PubMedCrossRefGoogle Scholar
  19. 19.
    J. Arklie, J. Taylor-Papadimitriou, W. F. Bodmer, et al., Differentiation antigens expressed by epithelial cells in the lactating breast are also detectable in breast cancers, Int. J. Cancer 28:23–26 (1981).PubMedCrossRefGoogle Scholar
  20. 20.
    J. Burchell, H. Durbin, and J. Taylor-Papadimitriou, Complexity of expression of antigenic determinants recognized by monoclonal antibodies HMFG1 and HMFG2 in normal and malignant human mammary epithelial cells, J. Immunol. 131:508–513 (1983).PubMedGoogle Scholar
  21. 21.
    A. A. Epenetos, C. C. Nimmon, J. Arklie, et al., Radioimmunodiagnosis of human cancer in an animal model using labeled tumor associated monoclonal antibodies, Br. J. Cancer 46:1–8 (1982).PubMedCrossRefGoogle Scholar
  22. 22.
    P. Travers and W. F. Bodmer, Preparation and characterization of monoclonal antibodies against placental alkaline phosphatase and other human trophoblast-associated determinants, Int. J. Cancer 33:633–641 (1984).PubMedCrossRefGoogle Scholar
  23. 23.
    F. J. Benham, M. S. Povey, and H. Harris, Placental-like alkaline phosphatase in malignant and benign ovarian tumors, Clin. Chim. Acta 86:201–215 (1978).PubMedCrossRefGoogle Scholar
  24. 24.
    C. A. Sunderland, J. O. Davies, and G. M. Stirrat, Immuno-histology of normal and ovarian cancer tissue with a monoclonal antibody to placental alkaline phosphatase, Cancer Res. 44:4496-4502 (1984).PubMedGoogle Scholar
  25. 25.
    P. J. Fraker and J. C. Speck, Protein and cell membrane iodination with a sparingly soluble chloramide, 1,3,4,6-tetrachloro-5,6-diphenylglycouril, Biochem. Biophys. Res. Commun. 80:849-857 (1978).CrossRefGoogle Scholar
  26. 26.
    W. S. Snyder, M. R. Ford, and G. G. Warner, Estimates of specific absorbed fractions for photon sources uniformly distributed in various organs of a heterogeneous photon, Medical International Radiation Dose (MIRD), Pamphlet 5 (revised), New York, Society of Nuclear Medicine, pp 5–67 (1978).Google Scholar
  27. 27.
    G. R. Hooker, D. Snook, N. Courtenay-Luck, et al., Antibody guided irradiation of lesions in advanced ovarian cancer with or without malignant ascites, Eur. J. Nucl. Med. 11:2/3, 34 (1985).Google Scholar
  28. 28.
    W. E. Lucas, M. Markham, and S. B. Howell, Intraperitoneal chemotherapy for advanced ovarian cancer, Am. J. Obstet. Gynaecol. 152:474–478 (1985).Google Scholar
  29. 29.
    R. F. Ozols, J. L. Speyer, J. Jenkins, and C. F. Myers, Phase II trial of 5-FU administered intraperitoneally to patients with refractory ovarian cancer, Cancer Treat. Rep. 68:1229–32 (1984).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Haralambos Kalofonos
    • 1
  • Agamemnon A. Epenetos
    • 1
  1. 1.Royal Postgraduate Medical SchoolHammersmith Hospital and Imperial Cancer Research FundLondonUK

Personalised recommendations