Phase I and pharmacokinetic study of intraperitoneal ormaplatin

Gynecol Oncol. 1993 Oct;51(1):72-7. doi: 10.1006/gyno.1993.1249.

Abstract

Ormaplatin is a cisplatin analog which has demonstrated activity against cisplatin-resistant tumors in preclinical studies. We delivered 28 cycles to 14 patients in a phase I trial of intraperitoneal ormaplatin given every 28 days. The maximum tolerated dose was 88.4 mg/m2 and acute dose-limiting toxicity was abdominal pain. Other toxicities include nausea, emisis, fever, and severe neuropathy seen in 1 patient at a cumulative dose of 399 mg/m2. No objective responses were observed. Hematologic toxicity was mild. The dose recommended for future trials of intraperitoneal ormaplatin is 66.5 mg/m2. Pharmacokinetic analysis performed at a dose of 66.5 mg/m2 demonstrated that the initial phase of elimination from the peritoneal cavity follows first-order kinetics with k = 0.69 hr-1 and half-life of 1.4 hr. Plasma pharmacokinetic behavior is best described by biexponential model with k1 = 0.369 hr-1, k2 = 0.107 hr-1, and first half-life of 2.9 hr and second half-life of 8.4 hr. Pharmacologic advantage, calculated by ratio of peritoneal to plasma AUC, is 17.1. If site-specific activity is demonstrated, then the intraperitoneal route of administration of ormaplatin at 66.5 mg/m2 may be beneficial.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics*
  • Catheters, Indwelling
  • Half-Life
  • Humans
  • Injections, Intraperitoneal
  • Middle Aged
  • Neoplasms / drug therapy
  • Organoplatinum Compounds / administration & dosage*
  • Organoplatinum Compounds / adverse effects
  • Organoplatinum Compounds / pharmacokinetics*

Substances

  • Antineoplastic Agents
  • Organoplatinum Compounds
  • ormaplatin