Summary
The currently accepted therapies for ovarian cancer have produced only limited numbers of extended complete remissions in advanced-stage disease. Studies of high-volume intraperitoneal chemotherapy have been initiated to define the toxicology, pharmacokinetics, and the therapeutic effectiveness of this treatment modality. This technique has been virtually ignored until recently, because little success has been achieved with it except in one study (Rutledge, 1966), in which large intraperitoneal fluid volumes were used. The general lack of success probably reflects inadequate attention to physiologic and pharmacologic principles of drug distribution and absorption in a space as large as the peritoneal cavity. Biomedical engineers, pharmacologists, and clinicians at the NCI have cooperated in the development of a rational chemotherapy for ovarian cancer. Following mathematical pharmacokinetic modeling and toxicologic studies in rat, a Phase I clinical trial of intraperitoneal methotrexate administered in large volumes of dialysis fluid was initiated. Results in three patients confirm the practicality of this approach, and further investigation is warranted.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Anderson, T., Young, R. C.: Recent advances in the staging and treatment of ovarian carcinoma. Med. Clin. N. Amer. 61, 1001 (1977)
Babb, A. L., Johansen, P. J., Strand, M. J., Tenckhoff, H., Scribner, B. H.: Bidirectional permeability of the human peritoneum to middle molecules. Proc. Europ. Dial. Transpl. Ass. 10, 247 (1973)
Bagley, C. M., Young, R. C., Canellos, G. P., DeVita, V. T.: Treatment of ovarian carcinoma: Possibilities for progress. New Engl. J. Med. 287, 856 (1972)
Bagley, C. M., Young, R. C., Schein, P. S., Chabner, B. A., DeVita, V. T.: Ovarian carcinoma metastatic to the diaphragm — frequently undiagnosed at laparotomy. Amer. J. Obstet. Gynec. 116, 397 (1973)
Chabner, B. A., Jacobs, S., Stoller. R. G., Hande, K., Young, R. C.: Methotrexate disposition in humans: Case studies in ovarian cancer and following high-dose infusion. Drug Metab. Rev. (in press, 1978)
Clark, D. G. C., Hilaris, B. S. et al.: Interdisciplinary approach to advanced ovarian cancer. Surg. Clin. N. Amer. 54, 897 (1974)
Clarkson, B., O'Conner, A., Winston, L., Hutchinson, D.: The physiologic dispositions of 5-fluorouracil and 5-fluoro-2′deoxyuridine in man. Clin. Pharmacol. Ther. 5, 581 (1964)
Dedrick, R. L., Zaharko, D. S., Bender, R. A., Bleyer, W. A., Lutz, R. J.: Pharmacokinetic considerations on resistance to anticancer drugs. Cancer Chemother. Rep. 59, 795 (1975)
Dedrick, R. L., Myers, C. E., Bugnay, P. M., DeVita, V. T.: Pharmacokinetic rationale for peritoneal drug administration in treatment of ovarian cancer. Cancer Chemother. Rep. 62, 1 (1978)
Fisher, R. I., Young, R. C.: Advances in the staging and treatment of ovarian cancer. Cancer 39, 967 (1977)
Fuks, F. Y.: External radiotherapy of ovarian cancer: Standard approaches and new frontiers. Semin. Oncol. 2, 253 (1975)
Garrett, E. R., Hurst, G. H., Green, J. R.: Kinetics and mechanisms of drug action on micro-organisms XXIII: Microbial kinetic assay for fluorouracil in biologic fluids and its application to human pharmacokinetics. J. pharm. Sci. 66, 1422 (1977)
Green, T. H.: Hemi-sulfur mustard in the palliation of patients with metastatic ovarian cancer. Obstet. and Gynec. 13, 383 (1959)
Hande, K. R., Balow, J. E., Drake, J. C., Rosenberg, S. A., Chabner, B. A.: Methotrexate and hemodialysis. Ann. intern. Med. 87, 495 (1977)
Hogben, C. A., Tocco, D. J., Brodie, B. G., Schanker, L. S.: On the mechanism of intestinal absorption of drugs. J. Pharmacol. exp. Ther. 275, 125 (1959)
Jaffe, N., Traggis, D.: Toxicity of high-dose methotrexate (NSC-740) and citrovorum factor (NSC-3590) in osteogenic sarcoma. Cancer Chemother. Rep. (Part 3) 6, 31 (1975)
Litterst, C. L., Gram, T. E., Dedrick, R. L., Guarino, A. M.: Distribution and disposition of platinum following IV administration of cis-diamine dichloroplatinum (II) to dogs. Cancer Res. 36, 2340 (1976)
Lukas, G., Brindle, S. D., Greengard, P.: The route of absorption of intraperitoneally administered compounds. J. Pharmacol. exp. Ther. 178, 562 (1971)
Michel, C. C.: Direct observation of sites of permeability for ions and small molecules in mesothelioma and endothelioma. In: Capillary Permeability, p. 623. Copenhagen: Scandinavia University Books 1969
Myers, C. W., Lippman, M. E., Eliot, H. M., Chabner, B. A.: Competitive protein binding assay for methotrexate. Proc. nat. Acad. Sci. (Wash.) 72, 3683 (1975)
Popovich, R. P., Moncrief, J. W., Dechard, J. J., Na, J. S., Sawyer, J. W.: Physiological transport parameters in patients in peritoneum and hemodialysis. In: Proc. 10th Annual Contractors Conference. Artificial Kidney-Chronic Uremia Program, p. 95. Bethesda: National Institute of Arthritis, Metabolism, and Digestive Diseases 1977
Rosenoff, S. H., Young, R. C., Anderson, T., Bagley, C., Chabner, B. A., Schein, P. S., DeVita, V. T.: Peritoneoscopy: a valuable tool for the initial staging and “second look” in ovarian carcinoma. Ann. intern. Med. 83, 37 (1975)
Rosenshaw, N., Blake, D., McIntyre, P. A., Parmley, T., Natarajan, T. K., Dvornicky, J., Nickoloff, E.: The effect of volume on the distribution of substances instilled into the peritoneal cavity. Gynecol. Oncol. (in press, 1978)
Rutledge, F., Burns, B. C.: Chemotherapy for advanced ovarian cancer. Comment by C. P. Hodgkinson. Amer. J. Obstet. Gynec. 96, 771 (1966)
Silberberg, E., Holleb, A. I.: Cancer statistics, 1971. Cancer 21, 13 (1971)
Sullivan, R. D., Miller, E., Furck, W. F.: Re-evaluation of methotrexate as an anticancer drug. Surg. Gynec. Obstet. 125, 819 (1967)
Tenckhoff, H., Schachter, H.: A bacteriologically safe peritoneal access device. Trans. Amer. Soc. artif. intern. Org. 14, 181 (1968)
Torres, I. J., Litterst, C. L., Guarino, A. M.: Transport of model compounds across the peritoneal membrane in the rat. Pharmacology (in press, 1978)
Young, R. C., Anderson, T.: Ovarian and testicular malignancies: Progress in management of tumors derived from the genital ridge. In: Recent Advances in Cancer Treatment, p. 325. New York: Raven Press 1977
Young, R. C., DeVita, V. T., Chabner, B. A.: A prospective trial of melphalan (PAM) and combination chemotherapy in advanced ovarian cancer. Proc. Amer. Soc. clin. Oncol. 12, 279 (1976)
Author information
Authors and Affiliations
Additional information
Clinical Pharmacology Branch, Division of Cancer Treatment
Laboratory of Toxicology, Division of Cancer Treatment
Biomedical Engineering and Instrumentation Branch, Division of Research Services
Medicine Branch, Division of Cancer Treatment
Division of Cancer Treatment
Rights and permissions
About this article
Cite this article
Jones, R.B., Myers, C.E., Guarino, A.M. et al. High volume intraperitoneal chemotherapy (“Belly bath”) for ovarian cancer. Cancer Chemother. Pharmacol. 1, 161–166 (1978). https://doi.org/10.1007/BF00253116
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00253116