Intraperitoneal cisplatin and cytarabine in the treatment of refractory or recurrent ovarian carcinoma.

Preclinical evaluation has suggested impressive concentration-dependent cytotoxic synergy between cisplatin and cytarabine in ovarian carcinoma. To further evaluate the clinical relevance of these observations, 39 patients with refractory or recurrent ovarian carcinoma were entered onto a phase II trial of intraperitoneal (IP) cisplatin (100 to 105 mg/m2 per course) plus cytarabine (600 to 900 mg per course). Treatment was administered over 2 or 3 days for a maximum of five monthly courses, followed by surgical reevaluation in patients without clinical evidence of disease. The 3-day regimen was discontinued secondary to the development of severe thrombocytopenia (five of 12 courses platelets decreased to less than 50,000/mm3). Additional toxicities included abdominal pain (moderate to severe at some time during therapy in 46% of patients), fever without evidence of infection (44%), and bacterial peritonitis (10%). Three patients declined surgical reassessment. Fourteen of 36 (39%; 95% confidence interval [CI], 23% to 55%) assessable patients demonstrated surgically defined responses, including 12 of 23 (52%; 95% CI, 32% to 72%) patients with tumor nodules less than 1 cm in diameter and only two of 13 (15%; 95% CI, 0% to 34%) patients with any lesion greater than 1 cm. There were seven (30%; 95% CI, 11% to 49%) surgically defined complete responses (CRs) in patients with less than 1 cm disease and none in patients with larger tumor nodules. IP cisplatin/cytarabine results in a high surgically defined response rate in patients with minimal residual ovarian carcinoma, but activity is low in patients with bulky intraabdominal disease.