Previous studies have shown that intraperitoneal (i.p.) floxuridine (FUDR) is tolerated at a dose of 3 g x 3 days given in 1.5-2 L of normal saline (NS). In a randomized phase II trial by the Southwest Oncology Group, this treatment was selected for further study because of a favorable 1-year progression-free survival. We have now evaluated ip FUDR in full doses combined with i.p. cisplatin given on the third day at a dose of 60 mg/m2 in 500 mL of NS. Intraperitoneal carboplatin was partially or fully substituted for i.p. cisplatin in patients with symptomatic neuropathies. All patients also received i.p. leucovorin, as previously piloted for fluoropyrimidine modulation. Seven patients with symptomatic ascites or measurable tumors were entered, as were 11 asymptomatic patients with minimal residual (< or = 1 cm) epithelial ovarian cancer. Six cycles of the combination of i.p. FUDR + cisplatin were completed in three patients; however, the combination of FUDR with both platinums was particularly well tolerated. Intraperitoneal FUDR + carboplatin (AUC of 5) was associated with some grade 3 and 4 thrombocytopenia and neutropenia. Eight of these 11 patients are alive, and 3 have been continuously with no evidence of disease exceeding 32 months. The regimen of i.p. FUDR + i.p. cisplatin (or i.p. FUDR with both platinums) is suitable for a phase III trial testing i.p. therapy either from the outset (e.g., i.p. up front) or after achieving clinical complete responses from initial treatment without intervening relapse (i.e., i.p. consolidation) in comparison to i.p. cisplatin.