Intraperitoneal chemotherapy: the use of concurrent systemic neutralizing agents

There is a very great pharmacologic advantage to the intraperitoneal administration of many agents active against human ovarian carcinoma. In principle, the use of a systemic neutralizing agent can further improve the therapeutic index of this approach. In the case of the cell cycle phase-specific antimetabolite methotrexate, systemic administration of leucovorin permits very long duration exposure to methotrexate. In the case of cisplatin, systemically administered thiosulfate appears to provide relatively specific protection for the kidneys, and this in turn permits a doubling of the plasma exposure to unneutralized cisplatin. These concepts are now ready for phase II trial.