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Related Experiment Videos

Intraperitoneal chemotherapy with cisplatin and melphalan.

M J Piccart1, J Abrams, P F Dodion

  • 1Service de Médecine, Université Libre de Brussels, Belgium.

Journal of the National Cancer Institute
|September 21, 1988
PubMed
Summary

Intraperitoneal cisplatin and melphalan show synergistic effects against ascites leukemia. This combination therapy demonstrated favorable pharmacokinetics and manageable toxicity in patients with intraperitoneal tumors, including ovarian cancer.

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Area of Science:

  • Oncology
  • Pharmacology
  • Cancer Research

Background:

  • Intraperitoneal (IP) chemotherapy offers potential for targeted drug delivery to the peritoneal cavity.
  • Cisplatin and melphalan are chemotherapeutic agents with known activity against various cancers.
  • Previous studies suggested synergistic effects and favorable pharmacokinetics for IP cisplatin and melphalan in preclinical models.

Purpose of the Study:

  • To evaluate the safety, tolerability, and pharmacokinetics of escalating doses of IP cisplatin and melphalan in patients with IP tumors.
  • To assess the efficacy of this combination therapy in patients with residual ovarian cancer.

Main Methods:

  • A Phase I clinical trial involving 30 patients with IP tumors, primarily residual ovarian cancer.
  • Administration of escalating doses of cisplatin (40-120 mg/m2) and melphalan (12-30 mg/m2) via IP infusion in 2 L 0.9% NaCl.

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  • Treatment cycles were administered every 28 days for one to nine cycles.
  • Pharmacokinetic analysis of peritoneal and plasma drug concentrations.
  • Assessment of dose-limiting toxicities, particularly myelosuppression.

    • Main Results:

    • Myelosuppression, specifically leukopenia, was the dose-limiting toxicity.
    • The maximum tolerated dose (MTD) was determined to be 120 mg/m2 for cisplatin and 20 mg/m2 for melphalan.
    • Non-hematologic toxicities, apart from nausea and vomiting, were mild, with minimal local toxicity.
    • Pharmacokinetic analysis revealed significantly higher peritoneal drug exposure compared to plasma (16-fold for cisplatin, 17-fold for melphalan).
    • Objective responses were observed in ovarian cancer patients with minimal residual disease (< 2 cm) upon third-look laparotomy.

    Conclusions:

    • Intraperitoneal cisplatin and melphalan combination therapy is feasible and demonstrates favorable pharmacokinetic properties in patients with IP tumors.
    • The MTD was established, and toxicity was generally manageable, with myelosuppression being dose-limiting.
    • The enhanced peritoneal drug exposure suggests a promising therapeutic potential for this regimen in managing IP malignancies, particularly ovarian cancer with minimal residual disease.