Intraperitoneal cytosine arabinoside therapy in ovarian carcinoma

Previous pharmacokinetic modeling has suggested that cytosine arabinoside (ara-C) may be an ideal agent for peritoneal administration in the treatment of intraabdominal neoplasms. In vitro drug sensitivity testing with clonogenic assays demonstrated sensitivity to the high concentrations of ara-C potentially achievable by intraperitoneal (IP) administration in five of nine patients with ovarian carcinoma. The kinetics of IP ara-C were then studied in three patients, and a 2 to 3 log concentration gradient was observed between the peritoneal compartment and plasma. Subsequently, the clinical efficacy of IP ara-C given for a five-day course every four weeks was evaluated in 10 patients with ovarian carcinoma who had failed systemic chemotherapy. Chemical peritonitis did not occur and systemic toxicity was minimal. Two patients were rendered free of disease and are alive without disease 14+ and 15+ months since therapy was discontinued. These results demonstrate that there is a very large pharmacologic advantage to the IP route of administration for ara-C, that ara-C is active against advanced ovarian carcinoma, and that the IP route of administration permits the cytokinetically rational use of very long durations of exposure for this cell-cycle phase-specific agent.