Intraperitoneal Chemotherapy and Immunotherapy

  • B. E. Wolf
  • P. H. Sugarbaker
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 110)


Treatment failures following putatively curative resections for circumscribed neoplasms are well recognized and the recurrence patterns have been analyzed. These observations compel us to reshape our conceptual model, for such cancers, from one of malignancy as a localized process to that of a regionalized process. Consequently, treatments should evolve to include not only the primary cancer (removedby surgery) but also the entire anatomic region (peritoneal cavity). Regionalized processes command a combined-modality approach to effect cure or, at least, to favorably alter the natural history of the disease. It follows, then, that if for a given neoplasm the available agents are not ideal and, furthermore, that no new agents have been developed in the recent past that offer a hope of improved survival ; we must exploit the agents at hand in the most effective manner.


Ovarian Cancer Peritoneal Cavity Peritoneal Carcinomatosis Intraperitoneal Chemotherapy Cytosine Arabinoside 
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.


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  1. 1.
    Clarkson B, O’Connor A, Wilson L et al. (1964) The physiologic disposition of 5-fluo-rouracil and 5-fluoro-2(l)-deoxyuridine in man. Clin Pharmacol Ther 5: 581–610PubMedGoogle Scholar
  2. 2.
    Chabner BA, Young RC (1973) Threshold methotrexate concentration for in vivo inhibition of DNA synthesis in normal and tumorous target tissues. J Clin Invest 52: 1804–1811PubMedCrossRefGoogle Scholar
  3. 3.
    Myers CE, Collins JM (1983) Pharmacology of intraperitoneal chemotherapy. Cancer Invest 1 (5): 395–407CrossRefGoogle Scholar
  4. 4.
    Dedrick RL, Myers CE, Bungay PM, DeVita VT (1978) Pharmacokinetic rationale for peritoneal drug administration in the treatment of ovarian cancer. Cancer Treat Rep 62: 1–11PubMedGoogle Scholar
  5. 5.
    Flessner MF, Dedrick RL, Schulte JS (1984) A distributed model of periotoneal plasma transport: theoretical considerations. Am J Physiol 246: R597–R607PubMedGoogle Scholar
  6. 6.
    Flessner MF, Fenstermacher JD, Blasberg RG, Dedrick RL (1985) Peritoneal absorption of macromolecules studied by quantitative autogradiography. Am J Physiol 248: H26–H32PubMedGoogle Scholar
  7. 7.
    Flessner MF, Fenstermacher JD, Blasberg RG (1985) A distributed model of peritoneal-plasma transport: tissue concentration gradients. Am J Physiol 248: F425–F435PubMedGoogle Scholar
  8. 8.
    Flessner MF, Dedrick RL, Schulte JS (1985) A distributed model of peritoneal-plasma transport: analysis of experimental data in the rat. Am J Physiol 248: F413–F424PubMedGoogle Scholar
  9. 9.
    Flessner MF, Dedrick RL, Schltz JS (1985) Exchange of macromolecules between peritoneal cavity and plasma. Am J Physiol: H15–H25Google Scholar
  10. 10.
    Dedrick RL (1985) Theoretical and experimental bases of intraperitoneal chemotherapy. Semin Oncol 12(3): 1–6PubMedGoogle Scholar
  11. 11.
    Speyer JL, Sugarbaker PH, Collin JM, Dedrick RL, Kleeker RW, Meyers CE (1981) Portal levels and hepatic clearance of 5-fluorouracil after intraperitoneal administration in humans. Cancer Res 41: pp 1916–1922PubMedGoogle Scholar
  12. 12.
    Sugarbaker PH, Gianola FJ, Speyer JL, Wesley R, Barofsky I, Meyers CE (1985) Prospective randomized trial of intravenous v intraperitoneal 5-FU in patients with a primary colon or rectal cancer. Semin Oncol 12(3): 101–111PubMedGoogle Scholar
  13. 13.
    Dedrick RL, Flessner MF, Collins JM et al. (1982) Is the peritoneum a membrane? ASAIO 5(1): 1–8Google Scholar
  14. 14.
    Dunnick NR, Jones RB, Doppman JL, Speyer J, Myers CE (1979) Intraperitoneal contrast infusion for assessment of intraperitoneal fluid dynamics. AJR 133: 221–223PubMedGoogle Scholar
  15. 15.
    Feldman GB, Knapp RI (1974) Lymphatic drainage of the peritoneal cavity and its significance in ovarian cancer. Am J Obstet Gynecol. 119: 991–994PubMedGoogle Scholar
  16. 16.
    Leichner PT, Rosenshein NB, Leibel SA et al. (1980) Distribution and tissue dose of in-traperitoneally administered radioactive chromic phosphate in New Zealand white rabbits. Radiology 134: 729–734PubMedGoogle Scholar
  17. 17.
    Rosenshein N, Blake D, McIntyre P et al. (1978) The effect of volume on the distribution of substances instilled into the peritoneal cavity. Gynecol Oncol 6: 106–110PubMedCrossRefGoogle Scholar
  18. 18.
    Teckhoff H, Schecter H (1968) A bacteriologically safe peritoneal access device. ASAO 12:181Google Scholar
  19. 19.
    Tenckhoff H (1974) Manual for chronic peritoneal dialysis. University of Washington School of Medicine, SeattleGoogle Scholar
  20. 20.
    Twardowski ZJ (1985) Intraperitoneal therapy in renal failure. Semin Oncol 12(3): 81–89PubMedGoogle Scholar
  21. 21.
    Piccart M J, Speyer JL, Markman M, ten Bokkel-Huinink WW, Alberts D, Jenkins J, Muggia F (1985) Intraperitoneal chemotherapy: technical experience at five institutions. Semin Oncol 12(3): 90–96PubMedGoogle Scholar
  22. 22.
    Jenkins J, Sugarbaker PH, Gianola FJ, Myers CE (1982) Technical considerations in the use of intraperitoneal chemotherapy administered by Tenckhoff catheter. Surg Gynecol Obstet 154: 858–864PubMedGoogle Scholar
  23. 23.
    Jenkins J (1983) Managing intraperitoneal chemotherapy: a medical, nursing and personal challenge. Semin Oncol 12(3): 97–100Google Scholar
  24. 24.
    Davis AS, Reed WP (1983) A leak-free technique for open insertion of peritoneal dialysis catheters. Surg Gynecol Obstet 157: 579–580PubMedGoogle Scholar
  25. 25.
    Cerilli J, Walker J, Bay W (1983) A new technique for placement of catheters for peritoneal dialysis. Sur Gynecol Obstet 156: 663–664Google Scholar
  26. 26.
    Ozols RF, Myers CE, Young RC (1984) Intraperitoneal chemotherapy. Ann Intern Med 100: 1 118–120Google Scholar
  27. 27.
    Longo DL, Young RC (1981) The natural history and treatment of ovarian cancer. Annu Rev Med 32: 475–490PubMedCrossRefGoogle Scholar
  28. 28.
    Buchsbaum HJ, Lifshitz S (1984) Staging and surgical evaluation of ovarian cancer. Semin Oncol 11(3): 227–237PubMedGoogle Scholar
  29. 29.
    Kavanagh JJ (1985) Investigational therapies for epithelial ovarian cancer. Clin Obstet Gynec 28(4): 846–852PubMedCrossRefGoogle Scholar
  30. 30.
    Young RC (1984) Ovarian cancer treatment: progress of paralysis? Semin Oncol 11(3): 327–329PubMedGoogle Scholar
  31. 31.
    Ozols RF, Young RC (1984) Chemotherapy of ovarian cancer. Semin Oncol 11(3): 251–263PubMedGoogle Scholar
  32. 32.
    Thigpen JT, Vance RB, Lodovico B, Khansur TF (1984) New drugs and experimental approaches in ovarian cancer treatment. Semin Oncol 11(3): 314–326PubMedGoogle Scholar
  33. 33.
    Hamilton TC, Young RC, Ozols RF (1984) Experimental model systems of ovarian cancer: applications to the design and evaluation of new teatment approaches. Semin Oncol 11(3): 285–298PubMedGoogle Scholar
  34. 34.
    Ozols R (1985) Intraperitoneal chemotherapy in the management of ovarian cancer. Semin Oncol 12(3): 75–80PubMedGoogle Scholar
  35. 35.
    Cohen CJ (1985) Surgical considerations in ovarian cancer. Semin Oncol 12(3): 53–56PubMedGoogle Scholar
  36. 36.
    Thigpen T, Blessing JA (1985) Current therapy of ovarian carcinoma: an overview. Semin Oncol 12(3): 47–52PubMedGoogle Scholar
  37. 37.
    Alberts DS, Young L, Mason N, Salmon SE (1985) In vitro evaluation of anticancer drugs against ovarian cancer at concentrations achievable by intraperitoneal administration. Semin Oncol 12(3): 38PubMedGoogle Scholar
  38. 39.
    Tong D, Russell AH, Dawson Le et al. (1983) Second laparotomy for proximal colon cancer. Am J Surg 145: 382–386PubMedCrossRefGoogle Scholar
  39. 40.
    Speyer JL (1985) The rationale behind intraperitoneal chemotherapy in gastrointestinal malignancies. Semin Oncol 12(3): 23–28PubMedGoogle Scholar
  40. 41.
    Douglass HO (1985) Gastric cancer: overview of current therapies. Semin Oncol 12(3): 57–62PubMedGoogle Scholar
  41. 42.
    Wilson RE (1985) Surgical considerations in gastric cancer. Semin Oncol 12(3): 63–68PubMedGoogle Scholar
  42. 43.
    Brenner DE (1986) Intraperitoneal chemotherapy: a review. J Clin Oncol 4(7): 1135–1147PubMedGoogle Scholar
  43. 44.
    Higgins GA Jr, Lyndon EL, Dwight RW, Keeher RJ (1978) The case of adjuvant 5-fluo-rouracil in colorectal cancer. Cancer Clin Trials, Spring: 35–41Google Scholar
  44. 45.
    Christophidis N, Vajda FJE, Lucas I, Drummer O, Moon WJ, Lornis WJ (1978) Fluorouracil therapy in patients with carcinoma of the large bowel: a pharmacokinetic comparison of various rates and routes of administration. Clin Pharmacokin 3: 33–336CrossRefGoogle Scholar
  45. 46.
    deBruijn EA, VanOosterom AT, Tjaden UR, Recuwijk HJEM, Pinedo HM (1985) Pharmacology of 5-deoxy-5-fluorouridine in patients with resistant ovarian cancer. Cancer Res 45: 5931–5935PubMedGoogle Scholar
  46. 47.
    Speyer JL, Collins JM, Dedrick RL, Brennan MF, Buckpitt AR, Londer H, DeVita VT, Myers CE (1980) Phase-I and pharmacological studies of 5-fluorouracil administration intraperitoneally. Cancer Res 40: 567–572PubMedGoogle Scholar
  47. 48.
    Jones RB, Collins JM, Myers CE, Brooks AE, Hubbard SM, Balow JE, Brennan MF, Dedrick RL, DeVita VT (1981) High-volume intraperitoneal chemotherapy with method-trexate in patients with cancer. Cancer Res 41: 55–59PubMedGoogle Scholar
  48. 49.
    Howel SB, Chu BB, Wung WE et al. (1981) Long-duration intracavitary infusion of methotrexate with systemic Leucovorin protection in patients with malignant effusions. J Clin Invest 67: 1161–1170CrossRefGoogle Scholar
  49. 50.
    Howell SB (1985) Intraperitoneal chemotherapy: the use of concurrent systemic neutralizing agents. Semin Oncol 12(3): 17–22PubMedGoogle Scholar
  50. 51.
    Ozols RF, Young RC (1985) High-dose cisplatin therapy in ovarian cancer. Semin Oncol 12(4): 21–30PubMedGoogle Scholar
  51. 52.
    Lopez JA, KrisKorian JG, Reich SD, Smyth RD, Lee FH, Isseil BF (1985) Clinical pharmacology of intraperitoneal cisplatin. Gynecol ncol 20: 1–9CrossRefGoogle Scholar
  52. 53.
    Makman M, Cleary S, Howells SB (1985) Nephrotoxicity of high-dose intracavitary cisplatin with intravenous thiosulfate protection. Eur J Cancer Clin Oncol 21 (9): 1015–1018CrossRefGoogle Scholar
  53. 54.
    Howell SB, Pfeifle CE, Wung WE, Olshen RA (1983) Intraperitoneal cis-diamminedich-loroplatinum with system thiosulfate protection. Cancer Res 43: 1426–1431PubMedGoogle Scholar
  54. 55.
    ten Bokkel-Huinink WW, Bubbelman R, Aartsen E, Franklin H, McVie JG (1985) Experimental and clinical results with intraperitoneal cisplatin. Semin Oncol 12(3): 43–46PubMedGoogle Scholar
  55. 56.
    Pretonius RG, Hacker NF, Berek JS, Ford LC, Hoeschele JD, Butler TA, LaGasse LD (1983) Pharmacokinetics of i.p. cisplatin in refractory ovarian carcinoma. Cancer Treat Rep 67(12): 1085–1092Google Scholar
  56. 57.
    Ozols RF, Young RC, Speyer JL et al. (1982) Phase-I and pharmacologic studies of adri-amycin administered intraperitoneally to patients with ovarian cancer. Cancer Res 42: 4265–4269PubMedGoogle Scholar
  57. 58.
    Howell SB, Pfeifle CE, Olshen, RA (1984) Intraperitoneal chemotherapy with melphal-an. Ann Int Med 101: 14–18PubMedGoogle Scholar
  58. 59.
    Holcenberg J, Anderson T, Ritch P et al. (1983) Intraperitoneal chemotherapy with mel-phalan plus glutaminase. Cancer Res 43: 1381–1388PubMedGoogle Scholar
  59. 60.
    King ME, Pfeifle CE, Howell SB (1984) Intraperitoneal cytosine arabinoside therapy in ovarian carcinoma. J Clin Oncol 2: 662–669PubMedGoogle Scholar
  60. 61.
    Markman M, Cleary S, Lucas WE, Howell SB (1985) Intraperitoneal chemotherapy with high-dose cisplatin and cytosine arabinoside for refractory ovarianm carcinoma and other malignancies principally involving the peritoneal cavity. J Clin Oncol 3: 7Google Scholar
  61. 62.
    Markman M (1985) Melphalan and cytarabine administered intraperitonealy as single agents and combination intraperitoneal chemotherapy with cisplatin and cytarabine. Semin Oncol 12(3): 33–37PubMedGoogle Scholar
  62. 63.
    Weiss G, Von Hoff DD (1985) Human tumor cloning assay: clinical applications for ovarian, gastric, pancreatic and colorectal cancers. Semin Oncol 12(3): 69–74PubMedGoogle Scholar
  63. 64.
    Berek JS, Hacker NF, Lichtenstein A, Jung T, Spina C, Knox RB, Brady J, Greene T, Ettinger LM, Lagasse LD, Bonnern EM, Spiegel RJ, Zigheboim J (1985) Intraperitoneal recombinant a-interferon for “salvage” immunotherapy in stage-III epithelial ovarian cancer: a Gynecologic Oncology Group Study. Cancer Res 45: 4447–4453PubMedGoogle Scholar
  64. 65.
    Lotze MT, Custer MC, Rosenberg SA (1987) Intraperitoneal administration of interleu-kin-2 in patients with cancer. Arch Surg (in press)Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1988

Authors and Affiliations

  • B. E. Wolf
    • 1
  • P. H. Sugarbaker
    • 1
  1. 1.Health Science CenterUniversity School of MedicineAtlantaUSA

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