High-dose cisplatin carboplatin chemotherapy in primary advanced epithelial ovarian cancer.

The purpose of the study was to maximize platinum dose intensity in women with ovarian cancer by combining cisplatin and carboplatin and using Day 1 and 8 scheduling. Thirty-two consecutive patients with primary stage 3 or 4 epithelial ovarian cancer underwent radical cytoreductive surgery followed by high-dose cisplatin carboplatin chemotherapy. Twenty-eight tumors (88%) were stage 3C or 4 and 20 (62%) were grade 3. Following radical cytoreductive surgery, 21 patients (66%) had less than 5 mm of residual disease. The first 2 patients treated with 75 mg/m2 cisplatin and 150 mg/m2 carboplatin on Days 1 and 8 every 28 days for 5 cycles developed severe and prolonged thrombocytopenia. As a result, the dose was reduced to 70 mg/m2 cisplatin and 100 mg/m2 carboplatin for the remaining 30 patients, representing a monthly platinum dose of 207 mg/m2. Projected platinum dose intensity was 700 mg/m2 cisplatin and 1000 mg/m2 carboplatin delivered over 16 weeks. Eleven patients (44%) received 100% and 27 patients (84%) received > 90% projected platinum dose intensity. Median projected platinum dose intensity received was 97%. Grade 4 thrombocytopenia occurred in 43 cycles (28%) and grade 3 peripheral neuropathy occurred in 15 patients (47%). Central nervous system toxicity occurred frequently: ototoxicity, 66%; decreased taste, 50%; optic toxicity, 41%; memory loss, 34%. Twenty-seven patients (84%) had a clinical complete response and 7 patients (44%) undergoing second-look laparotomy had a pathologic complete response. The majority of clinical responses were based on CA-125. Median survival has not been reached at 2.1 years. Median progression-free survival is 1.4 years. Combining cisplatin and carboplatin using Day 1 and 8 scheduling allows maximum hematologic platinum dose intensity; however, peripheral neuropathy is prohibitive. Day 1 and 8 scheduling does not appear to prevent peripheral neuropathy when delivering dose-intense platinum chemotherapy. Central nervous system toxicity of high-dose platinum is more common than previously reported.