A phase I/II study of intraperitoneally administered doxorubicin entrapped in cardiolipin liposomes in patients with ovarian cancer.

A phase I and II clinical trial of intraperitoneally administered liposome-encapsulated doxorubicin in patients with advanced ovarian cancer is being evaluated. Doxyrubicin liposomes were prepared with cardiolipin, phosphatidyl choline, cholesterol, and sterarylamine and sized by flow cytometry before administration. Fifteen patients have been treated with 42 cycles of intraperitoneal liposome-encapsulated doxrubicin. Liposome-encapsulated doxorubicin in 2 L of normal saline solution was infused over 1 hour through an infusaport into the peritoneal cavity with a dwell time of 4 hours every 21 days. Liposome-encapsulated doxorubicin has been administered at escalating doses up to 100 mg/2 L and has been well tolerated. Increased bowel motility with mild-to-moderate abdominal distress has been encountered during the first 24 hours after administration. There has been one patient with presumed chemically induced peritonitis after a temperature elevation to 39.5 degrees C. There has been no myelosuppression, abnormalities of liver function tests, or alopecia. Nausea and vomiting were minimal. Liposome-encapsulated doxorubicin was extravasated in two patients without sequelae. Drug levels were measured after completion of infusion. At a dose of 70 mg, the peak intraperitoneal concentration was 28.6 micrograms/microliter, which was reduced to 23.6 micrograms/microliter by 2 hours. Concurrent plasma levels were in the range of 0.2 to 0.5 micrograms/microliter. A similar pattern was observed at other doses. The maximum tolerable dose has not yet been obtained. There were three responders in the 10 evaluable patients. The preliminary experience with intraperitoneal liposome-encapsulated doxorubicin is encouraging.