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. 1989 Jul-Aug;62(4):393–403.

Intraperitoneal therapy in the management of ovarian carcinoma.

M Markman 1, T Hakes 1, B Reichman 1, W Hoskins 1, S Rubin 1, W Jones 1, L Almadones 1, J L Lewis Jr 1
PMCID: PMC2589079  PMID: 2688324

Abstract

The intraperitoneal administration of chemotherapeutic and biological agents as therapy of ovarian carcinoma is based on both theoretical considerations and experimental evaluations which suggest that tumor present in the cavity can be exposed to higher concentrations of certain antineoplastic drugs than can be accomplished if the agents are administered systemically. Recent clinical data have confirmed both the safety and pharmacokinetic advantage associated with this approach. Surgically defined responses have been observed in patients with small-volume residual refractory ovarian carcinoma treated with several single-agent and combination intraperitoneal therapeutic programs. While significant activity has been noted in this clinical setting, a clearly defined role for intraperitoneal treatment in the standard management of ovarian carcinoma remains to be determined.

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Selected References

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  1. Alberts D. S., Garcia-Kendall D., Surwit E. A. Phase II trial of mitomycin C plus 5-FU in the treatment of drug-refractory ovarian cancer. Semin Oncol. 1988 Jun;15(3 Suppl 4):22–26. [PubMed] [Google Scholar]
  2. Alberts D. S., Surwit E. A., Peng Y. M., McCloskey T., Rivest R., Graham V., McDonald L., Roe D. Phase I clinical and pharmacokinetic study of mitoxantrone given to patients by intraperitoneal administration. Cancer Res. 1988 Oct 15;48(20):5874–5877. [PubMed] [Google Scholar]
  3. Alberts D. S., Young L., Mason N., Salmon S. E. In vitro evaluation of anticancer drugs against ovarian cancer at concentrations achievable by intraperitoneal administration. Semin Oncol. 1985 Sep;12(3 Suppl 4):38–42. [PubMed] [Google Scholar]
  4. Batist G., Ihde D. C., Zabell A., Lichter A. S., Veach S. R., Cohen M. H., Carney D. N., Bunn P. A. Small-cell carcinoma of lung: reinduction therapy after late relapse. Ann Intern Med. 1983 Apr;98(4):472–474. doi: 10.7326/0003-4819-98-4-472. [DOI] [PubMed] [Google Scholar]
  5. Berek J. S., Hacker N. F., Lichtenstein A., Jung T., Spina C., Knox R. M., Brady J., Greene T., Ettinger L. M., Lagasse L. D. Intraperitoneal recombinant alpha-interferon for "salvage" immunotherapy in stage III epithelial ovarian cancer: a Gynecologic Oncology Group Study. Cancer Res. 1985 Sep;45(9):4447–4453. [PubMed] [Google Scholar]
  6. Casper E. S., Kelsen D. P., Alcock N. W., Lewis J. L., Jr Ip cisplatin in patients with malignant ascites: pharmacokinetic evaluation and comparison with the iv route. Cancer Treat Rep. 1983 Mar;67(3):235–238. [PubMed] [Google Scholar]
  7. Creech R. H., Shah M. K., Catalano R. B., Dierks K., Dayal H., Goldberg-Alberts R. Phase II study of low-dose mitomycin in patients with ovarian cancer previously treated with chemotherapy. Cancer Treat Rep. 1985 Nov;69(11):1271–1273. [PubMed] [Google Scholar]
  8. Dedrick R. L., Myers C. E., Bungay P. M., DeVita V. T., Jr Pharmacokinetic rationale for peritoneal drug administration in the treatment of ovarian cancer. Cancer Treat Rep. 1978 Jan;62(1):1–11. [PubMed] [Google Scholar]
  9. Demicheli R., Bonciarelli G., Jirillo A., Foroni R., Petrosino L., Targa L., Garusi G. Pharmacologic data and technical feasibility of intraperitoneal doxorubicin administration. Tumori. 1985 Feb 28;71(1):63–68. doi: 10.1177/030089168507100112. [DOI] [PubMed] [Google Scholar]
  10. Dunnick N. R., Jones R. B., Doppman J. L., Speyer J., Myers C. E. Intraperitoneal contrast infusion for assessment of intraperitoneal fluid dynamics. AJR Am J Roentgenol. 1979 Aug;133(2):221–223. doi: 10.2214/ajr.133.2.221. [DOI] [PubMed] [Google Scholar]
  11. Durand R. E. Flow cytometry studies of intracellular adriamycin in multicell spheroids in vitro. Cancer Res. 1981 Sep;41(9 Pt 1):3495–3498. [PubMed] [Google Scholar]
  12. Fisher R. I., DeVita V. T., Hubbard S. P., Simon R., Young R. C. Prolonged disease-free survival in Hodgkin's disease with MOPP reinduction after first relapse. Ann Intern Med. 1979 May;90(5):761–763. doi: 10.7326/0003-4819-90-5-761. [DOI] [PubMed] [Google Scholar]
  13. GREEN T. H., Jr Hemisulfur mustard in the palliation of patients with metastatic ovarian carcinoma. Obstet Gynecol. 1959 Apr;13(4):383–393. doi: 10.1097/00006250-195904000-00001. [DOI] [PubMed] [Google Scholar]
  14. Gyves J. Pharmacology of intraperitoneal infusion 5-fluorouracil and mitomycin-C. Semin Oncol. 1985 Sep;12(3 Suppl 4):29–32. [PubMed] [Google Scholar]
  15. Hacker N. F., Berek J. S., Pretorius R. G., Zuckerman J., Eisenkop S., Lagasse L. D. Intraperitoneal cis-platinum as salvage therapy for refractory epithelial ovarian cancer. Obstet Gynecol. 1987 Nov;70(5):759–764. [PubMed] [Google Scholar]
  16. Henderson E. S. Treatment strategies for "high-risk" leukemia. J Clin Oncol. 1987 May;5(5):689–691. doi: 10.1200/JCO.1987.5.5.689. [DOI] [PubMed] [Google Scholar]
  17. Holcenberg J., Anderson T., Ritch P., Skibba J., Howser D., Ring B., Adams S., Helmsworth M. Intraperitoneal chemotherapy with melphalan plus glutaminase. Cancer Res. 1983 Mar;43(3):1381–1388. [PubMed] [Google Scholar]
  18. Howell S. B., Chu B. B., Wung W. E., Metha B. M., Mendelsohn J. Long-duration intracavitary infusion of methotrexate with systemic leucovorin protection in patients with malignant effusions. J Clin Invest. 1981 Apr;67(4):1161–1170. doi: 10.1172/JCI110130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Howell S. B., Pfeifle C. E., Olshen R. A. Intraperitoneal chemotherapy with melphalan. Ann Intern Med. 1984 Jul;101(1):14–18. doi: 10.7326/0003-4819-101-1-14. [DOI] [PubMed] [Google Scholar]
  20. Howell S. B., Pfeifle C. L., Wung W. E., Olshen R. A., Lucas W. E., Yon J. L., Green M. Intraperitoneal cisplatin with systemic thiosulfate protection. Ann Intern Med. 1982 Dec;97(6):845–851. doi: 10.7326/0003-4819-97-6-845. [DOI] [PubMed] [Google Scholar]
  21. Jenkins J., Sugarbaker P. H., Gianola F. J., Myers C. E. Technical considerations in the use of intraperitoneal chemotherapy administered by Tenckhoff catheter. Surg Gynecol Obstet. 1982 Jun;154(6):858–862. [PubMed] [Google Scholar]
  22. Jones R. B., Collins J. M., Myers C. E., Brooks A. E., Hubbard S. M., Balow J. E., Brennan M. F., Dedrick R. L., DeVita V. T. High-volume intraperitoneal chemotherapy with methotrexate in patients with cancer. Cancer Res. 1981 Jan;41(1):55–59. [PubMed] [Google Scholar]
  23. Kaplan R. A., Markman M., Lucas W. E., Pfeifle C., Howell S. B. Infectious peritonitis in patients receiving intraperitoneal chemotherapy. Am J Med. 1985 Jan;78(1):49–53. doi: 10.1016/0002-9343(85)90461-9. [DOI] [PubMed] [Google Scholar]
  24. Katz M. E., Schwartz P. E., Kapp D. S., Luikart S. Epithelial carcinoma of the ovary: current strategies. Ann Intern Med. 1981 Jul;95(1):98–111. doi: 10.7326/0003-4819-95-1-98. [DOI] [PubMed] [Google Scholar]
  25. King M. E., Pfeifle C. E., Howell S. B. Intraperitoneal cytosine arabinoside therapy in ovarian carcinoma. J Clin Oncol. 1984 Jun;2(6):662–669. doi: 10.1200/JCO.1984.2.6.662. [DOI] [PubMed] [Google Scholar]
  26. Lawton F., Blackledge G., Mould J., Latief T., Watson R., Chetiyawardana A. D. Phase II study of mitoxantrone in epithelial ovarian cancer. Cancer Treat Rep. 1987 Jun;71(6):627–629. [PubMed] [Google Scholar]
  27. Lopez J. A., Krikorian J. G., Reich S. D., Smyth R. D., Lee F. H., Issell B. F. Clinical pharmacology of intraperitoneal cisplatin. Gynecol Oncol. 1985 Jan;20(1):1–9. doi: 10.1016/0090-8258(85)90118-0. [DOI] [PubMed] [Google Scholar]
  28. Lukas G., Brindle S. D., Greengard P. The route of absorption of intraperitoneally administered compounds. J Pharmacol Exp Ther. 1971 Sep;178(3):562–564. [PubMed] [Google Scholar]
  29. Markman M., Cleary S., Lucas W. E., Howell S. B. Intraperitoneal chemotherapy with high-dose cisplatin and cytosine arabinoside for refractory ovarian carcinoma and other malignancies principally involving the peritoneal cavity. J Clin Oncol. 1985 Jul;3(7):925–931. doi: 10.1200/JCO.1985.3.7.925. [DOI] [PubMed] [Google Scholar]
  30. Markman M., Cleary S., Lucas W., Weiss R., Howell S. B. Ip chemotherapy employing a regimen of cisplatin, cytarabine, and bleomycin. Cancer Treat Rep. 1986 Jun;70(6):755–760. [PubMed] [Google Scholar]
  31. Markman M., Howell S. B., Lucas W. E., Pfeifle C. E., Green M. R. Combination intraperitoneal chemotherapy with cisplatin, cytarabine, and doxorubicin for refractory ovarian carcinoma and other malignancies principally confined to the peritoneal cavity. J Clin Oncol. 1984 Dec;2(12):1321–1326. doi: 10.1200/JCO.1984.2.12.1321. [DOI] [PubMed] [Google Scholar]
  32. Markman M. Intracavitary administration of biological agents. J Biol Response Mod. 1987 Aug;6(4):404–411. [PubMed] [Google Scholar]
  33. Markman M. Intraperitoneal antineoplastic agents for tumors principally confined to the peritoneal cavity. Cancer Treat Rev. 1986 Dec;13(4):219–242. doi: 10.1016/0305-7372(86)90007-1. [DOI] [PubMed] [Google Scholar]
  34. McVie J. G., ten Bokkel Huinink W., Dubbelman R., Franklin H., van der Vijgh W., Klein I. Phase I study and pharmacokinetics of intraperitoneal carboplatin. Cancer Treat Rev. 1985 Sep;12 (Suppl A):35–41. doi: 10.1016/0305-7372(85)90016-7. [DOI] [PubMed] [Google Scholar]
  35. Monk B. J., Surwit E. A., Alberts D. S., Graham V. Intraperitoneal mitomycin C in the treatment of peritoneal carcinomatosis following second-look surgery. Semin Oncol. 1988 Jun;15(3 Suppl 4):27–31. [PubMed] [Google Scholar]
  36. Nederman T., Carlsson J. Penetration and binding of vinblastine and 5-fluorouracil in cellular spheroids. Cancer Chemother Pharmacol. 1984;13(2):131–135. doi: 10.1007/BF00257130. [DOI] [PubMed] [Google Scholar]
  37. Ozols R. F., Grotzinger K. R., Fisher R. I., Myers C. E., Young R. C. Kinetic characterization and response to chemotherapy in a transplantable murine ovarian cancer. Cancer Res. 1979 Aug;39(8):3202–3208. [PubMed] [Google Scholar]
  38. Ozols R. F., Locker G. Y., Doroshow J. H., Grotzinger K. R., Myers C. E., Fisher R. I., Young R. C. Chemotherapy for murine ovarian cancer: a rationale for ip therapy with adriamycin. Cancer Treat Rep. 1979 Feb;63(2):269–273. [PubMed] [Google Scholar]
  39. Ozols R. F., Locker G. Y., Doroshow J. H., Grotzinger K. R., Myers C. E., Young R. C. Pharmacokinetics of adriamycin and tissue penetration in murine ovarian cancer. Cancer Res. 1979 Aug;39(8):3209–3214. [PubMed] [Google Scholar]
  40. Ozols R. F. Pharmacologic reversal of drug resistance in ovarian cancer. Semin Oncol. 1985 Sep;12(3 Suppl 4):7–11. [PubMed] [Google Scholar]
  41. Ozols R. F., Speyer J. L., Jenkins J., Myers C. E. Phase II trial of 5-FU administered Ip to patients with refractory ovarian cancer. Cancer Treat Rep. 1984 Oct;68(10):1229–1232. [PubMed] [Google Scholar]
  42. Ozols R. F., Young R. C., Speyer J. L., Sugarbaker P. H., Greene R., Jenkins J., Myers C. E. Phase I and pharmacological studies of adriamycin administered intraperitoneally to patients with ovarian cancer. Cancer Res. 1982 Oct;42(10):4265–4269. [PubMed] [Google Scholar]
  43. Pater J. L., Carmichael J. A., Krepart G. V., Fraser R. C., Roy M., Kirk M. E., Levitt M., Brown L. B., Wilson K. S., Shelley W. E. Second-line chemotherapy of stage III-IV ovarian carcinoma: a randomized comparison of melphalan to melphalan and hexamethylmelamine in patients with persistent disease after doxorubicin and cisplatin. Cancer Treat Rep. 1987 Mar;71(3):277–281. [PubMed] [Google Scholar]
  44. Pfeifle C. E., Howell S. B., Markman M., Lucas W. E. Totally implantable system for peritoneal access. J Clin Oncol. 1984 Nov;2(11):1277–1280. doi: 10.1200/JCO.1984.2.11.1277. [DOI] [PubMed] [Google Scholar]
  45. Piccart M. J., Abrams J., Dodion P. F., Crespeigne N., Sculier J. P., Pector J. C., Finet C., Nouwijnck C., Bondue H., Atassi G. Intraperitoneal chemotherapy with cisplatin and melphalan. J Natl Cancer Inst. 1988 Sep 21;80(14):1118–1124. doi: 10.1093/jnci/80.14.1118. [DOI] [PubMed] [Google Scholar]
  46. Piver M. S., Lele S. B., Marchetti D. L., Baker T. R., Emrich L. J., Hartman A. B. Surgically documented response to intraperitoneal cisplatin, cytarabine, and bleomycin after intravenous cisplatin-based chemotherapy in advanced ovarian adenocarcinoma. J Clin Oncol. 1988 Nov;6(11):1679–1684. doi: 10.1200/JCO.1988.6.11.1679. [DOI] [PubMed] [Google Scholar]
  47. Pretorius R. G., Hacker N. F., Berek J. S., Ford L. C., Hoeschele J. D., Butler T. A., Lagasse L. D. Pharmacokinetics of Ip cisplatin in refractory ovarian carcinoma. Cancer Treat Rep. 1983 Dec;67(12):1085–1092. [PubMed] [Google Scholar]
  48. Roboz J., Jacobs A. J., Holland J. F., Deppe G., Cohen C. J. Intraperitoneal infusion of doxorubicin in the treatment of gynecologic carcinomas. Med Pediatr Oncol. 1981;9(3):245–250. doi: 10.1002/mpo.2950090307. [DOI] [PubMed] [Google Scholar]
  49. Rosenshein 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. 1978 Feb;6(1):106–110. doi: 10.1016/0090-8258(78)90010-0. [DOI] [PubMed] [Google Scholar]
  50. Runowicz C. D., Dottino P. R., Shafir M. K., Mark M. A., Cohen C. J. Catheter complications associated with intraperitoneal chemotherapy. Gynecol Oncol. 1986 May;24(1):41–50. doi: 10.1016/0090-8258(86)90006-5. [DOI] [PubMed] [Google Scholar]
  51. Seltzer V., Vogl S., Kaplan B. Recurrent ovarian carcinoma: retreatment utilizing combination chemotherapy including cis-diamminedichloroplatinum in patients previously responding to this agent. Gynecol Oncol. 1985 Jun;21(2):167–176. doi: 10.1016/0090-8258(85)90249-5. [DOI] [PubMed] [Google Scholar]
  52. Shenkenberg T. D., Von Hoff D. D. Mitoxantrone: a new anticancer drug with significant clinical activity. Ann Intern Med. 1986 Jul;105(1):67–81. doi: 10.7326/0003-4819-105-1-67. [DOI] [PubMed] [Google Scholar]
  53. Speyer J. L., Collins J. M., Dedrick R. L., Brennan M. F., Buckpitt A. R., Londer H., DeVita V. T., Jr, Myers C. E. Phase I and pharmacological studies of 5-fluorouracil administered intraperitoneally. Cancer Res. 1980 Mar;40(3):567–572. [PubMed] [Google Scholar]
  54. Stanhope C. R., Smith J. P., Rutledge F. Second trial drugs in ovarian cancer. Gynecol Oncol. 1977 Mar;5(1):52–58. doi: 10.1016/0090-8258(77)90007-5. [DOI] [PubMed] [Google Scholar]
  55. WEISBERGER A. S., LEVINE B., STORAASLI J. P. Use of nitrogen mustard in treatment of serous effusions of neoplastic origin. J Am Med Assoc. 1955 Dec 31;159(18):1704–1707. doi: 10.1001/jama.1955.02960350004002. [DOI] [PubMed] [Google Scholar]
  56. West G. W., Weichselbaum R., Little J. B. Limited penetration of methotrexate into human osteosarcoma spheroids as a proposed model for solid tumor resistance to adjuvant chemotherapy. Cancer Res. 1980 Oct;40(10):3665–3668. [PubMed] [Google Scholar]
  57. Wharton J. T., Edwards C. L., Rutledge F. N. Long-term survival after chemotherapy for advanced epithelial ovarian carcinoma. Am J Obstet Gynecol. 1984 Apr 1;148(7):997–1005. doi: 10.1016/0002-9378(84)90543-x. [DOI] [PubMed] [Google Scholar]
  58. Zimm S., Cleary S. M., Lucas W. E., Weiss R. J., Markman M., Andrews P. A., Schiefer M. A., Kim S., Horton C., Howell S. B. Phase I/pharmacokinetic study of intraperitoneal cisplatin and etoposide. Cancer Res. 1987 Mar 15;47(6):1712–1716. [PubMed] [Google Scholar]
  59. ten Bokkel Huinink W. W., Dubbelman R., Aartsen E., Franklin H., McVie J. G. Experimental and clinical results with intraperitoneal cisplatin. Semin Oncol. 1985 Sep;12(3 Suppl 4):43–46. [PubMed] [Google Scholar]

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