title: High-dose cisplatin carboplatin chemotherapy in primary advanced epithelial ovarian cancer.
abstract: 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.
authors.affiliation: Division of Gynecologic Oncology, Southern Illinois University School of Medicine, Springfield 62794.
authors.forename: J
authors.initials: J
authors.lastname: Fanning
authors.forename: R D
authors.initials: RD
authors.lastname: Hilgers
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000601:surgery; D011446:Prospective Studies
chemical_list: D016190:Carboplatin; D002945:Cisplatin