Phase I study of intraperitoneal carboplatin as adjuvant therapy in early ovarian cancer

Early stage poor-risk ovarian cancer patients are at considerable risk for recurrent disease. Adjuvant radio- or chemotherapy has been found to improve disease-free and overall survival. Carboplatin, a second generation platinum, is documented comparable in efficacy to cisplatin in patients with advanced ovarian cancer. The toxicity profile is different from that of cisplatin. Dose-limiting toxicity is myelosuppression. The incidence and grade of renal and neurological toxicity is much lower compared with cisplatin, as is nausea and vomiting. Carboplatin given intraperitoneally (ip) is shown to have a favorable theoretical therapeutic advantage compared with iv administration since the peak peritoneal cavity/peak plasma concentration ratio is 18. Patients with early stage ovarian cancer seem suitable for carboplatin ip treatment. The study was designed to find the maximal tolerated dose (MTD). Three new patients were given two courses at each dose level. The MTD found was confirmed with further patients. Carboplatin was given in 2 liters of glucose via a subcutaneous implantable port without removal of fluid from the cavity. The starting dose was 300 mg/m2. Dose-limiting toxicity was thrombocytopenia and leukopenia. Leukocyte and platelet counts were reconstituted within 28 days in all cases. One case of severe but transient nephrotoxicity was observed. MTD was determined to 500 mg/m2.