Intraperitoneal Chemotherapy with Melphalan

Abstract

Melphalan was administered by the i.p. route to investigate its toxicity and pharmacokinetics. The drug was instilled with 2 l of fluid and allowed to dwell in the peritoneal cavity for 4 h. No local toxicity was detected by clinical examination, laboratory tests or histologic examination. The i.p. route allowed for an increase in the dose to .apprx. 3 times the maximum dose tolerated i.v. before drug leaking into the systemic circulation produced dose-limiting myelosuppression. The peak peritoneal concentration averaged 93-fold greater than the plasma concentration; total drug exposure for the peritoneal cavity averaged 63-fold greater than that for plasma. Tumor regressions were observed in patients with ovarian carcinoma and gastrointestinal adenocarcinomas. From the pharmacologic point of view, if any portion of the tumor can be reached by i.p. instillation, then there is a very strong rationale for the administration of melphalan by the i.p. route, rather than the oral or i.v. route, for the treatment of tumors confined to the peritoneal cavity.