A phase I-II study with intraperitoneal cisplatin plus systemic etoposide in patients with minimal residual ovarian...

In patients with residual ovarian cancer after standard platinum-based induction, dose intensification was achieved by intraperitoneal administration of cisplatin 90 mg/m2 with intravenous Na thiosulphate and increasing dosages of etoposide. 40 patients entered the study, 4 on 200 mg/m2, 6 on 400 mg/m2, 22 on 600 mg/m2 and 8 on 800 mg/m2 etoposide. The optimal dose for etoposide was 600 mg/m2. 29 patients on the two highest dose steps were evaluable for response. 14 patients reached a complete remission, which was surgically confirmed in 6. All these patients initially had tumour residuals smaller than 1 cm. 3 patients had a partial response, 4 had stable disease and 8 progressed. At a maximal follow-up of 2 years (median 12 months), median time to progression was 12 months and median overall survival was 14 months. Of the 14 patients with complete remission, 2 relapsed at 9 and 11 months. Apart from a rash, in 4 of 22 patients at 600 mg/m2 and in 5 of 8 at 800 mg/m2 etoposide, the main toxicity was leukopenia grade 3-4 in 58% of cycles on 600 and in 76% at 800 mg/m2 etoposide. Leukopenic fever, however, occurred only three times; thrombocytopenia was rare. Cycles had to be delayed sporadically and the etoposide dose was reduced in 9% of all cycles at 600 and in 11% at 800 mg/m2. Intraperitoneal instillation of cisplatin gave no peritoneal symptoms. Intraperitoneal cisplatin with intravenous etoposide was tolerable and effective for patients with small tumour residuals after induction for stage III ovarian cancer.