A PHASE-II TRIAL OF INTRAPERITONEAL HIGH-DOSE CARBOPLATIN AND ETOPOSIDE WITH GRANULOCYTE MACROPHAGE-COLONY-STIMULATING FACTOR SUPPORT IN PATIENTS WITH OVARIAN-CARCINOMA

Based upon results obtained in a Phase I study, we conducted a Phase I I trial of high-dose CBDCA and etoposide administered via the intraper itoneal (IP) route in patients with ovarian cancer. CBDCA at a dose of 600 mg/m2 and etoposide at a dose of 400 mg/m2 were administered rapi dly into the peritoneal cavity. The total dose of each agent was calcu lated and given daily over 3 days in amounts equal to one-third of the total dose. On day 1 of therapy, one-third of the dose was mixed in 2 liters of D5W and administered intraperitoneally as rapidly as possib le. On days 2 and 3, one-third of the dose was mixed in 1 liter of D5W and administered similarly. GM-CSF was begun on day 4 as a subcutaneo us injection at a dose of 500 mug/m2/day. A total 53 courses of treatm ent was administered to 18 patients; 9 of 13 patients (69%) with evalu able disease demonstrated evidence consistent with a partial response; however, the majority were response determined by a decrease in tumor marker (CA-125). One patient who had pathologic evidence of disease a t second look laparotomy, but no measurable disease, was treated and s hown at subsequent reexploration to have no further evidence of diseas e. This patient remains free of disease at 17+ months. The toxicity en countered in this trial was formidable, resulting in the removal of 78 % of the patients from the study prior to completing 6 cycles of thera py.