Intraperitoneal Cisplatin with Systemic Thiosulfate Protection

  1. STEPHEN B. HOWELL, M.D.;
  2. CRAIG L. PFEIFLE, Pharm.D.;
  3. WALLY E. WUNG, Ph.D.;
  4. RICHARD A. OLSHEN, Ph.D.;
  5. WILLIAM E. LUCAS, M.D.;
  6. JOSEPH L. YON, M.D.; and
  7. MARK GREEN, M.D.
  1. La Jolla, California

    Abstract

    Seventeen patients with intraperitoneal tumors were treated by 4-hour intraperitoneal dialysis with cisplatin alone, or in combination with an intravenous neutralizing agent, sodium thiosulfate. Cisplatin alone, 90 mg/m2 body surface area intraperitoneally, produced nephrotoxicity. When intraperitoneal cisplatin therapy was combined with intravenous thiosulfate treatment, the dose of cisplatin could be escalated to 270 mg/m2 body surface area without causing an increase in serum creatinine levels or undue myelosuppression. Even at doses up to 270 mg/m2, no local toxicity occurred. The peak peritoneal concentration of free reactive cisplatin averaged 21-fold higher than the plasma level, and the area under the peritoneal cisplatin elimination curve averaged 12-fold more than the area under the plasma curve. Neither of these ratios varied significantly with cisplatin dose. Regression of intraperitoneal tumor masses was observed in patients with far-advanced ovarian carcinoma, mesothelioma, and malignant carcinoid.

    Article and Author Information

    • ▸From the Departments of Medicine, Gynecologic Oncology, Pharmacy, and Mathematics, and the Cancer Center; University of California, San Diego; La Jolla, California.

    • Grant support: in part by grants CA-23100 and CA-26666, National Institutes of Health; and grant RR-00827, University of California, San Diego, General Clinical Research Center, National Institutes of Health/Division of Resources. This research was conducted in part by the Clayton Foundation for Research, California Division. Dr. Howell is a Clayton Foundation Investigator. Drugs for this study were provided by Bristol Laboratories, Syracuse, New York, and Eli Lilly & Company, Indianapolis, Indiana.

    • ▸Requests for reprints should be addressed to Stephen B. Howell, M.D.; Department of Medicine T-006, University of California, San Diego; La Jolla, CA 92093.

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    1. Ann Intern Med December 1, 1982 vol. 97 no. 6 845-851
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