title: Dose-dense cisplatin/paclitaxel. a well-tolerated and highly effective chemotherapeutic regimen in patients with advanced ovarian cancer.
abstract: A randomised phase I/II trial with weekly cisplatin 70 mg/m(2) (days 1, 8, 15, 29, 36, 43) in combination with escalating doses of paclitaxel either 4-weekly or weekly was conducted in 49 patients with ovarian cancer; patients were chemotherapy-nai;ve or had a first relapse after platinum-based chemotherapy. Paclitaxel could be safely escalated to 225 mg/m(2) 4-weekly or 100 mg/m(2) weekly, with fatigue as the major adverse event. Myelosuppression, renal toxicity and neurotoxicity were mild to moderate. Pharmacokinetic analysis showed an approximately 2-fold reduction of DNA-adduct formation in leucocytes compared with cisplatin without paclitaxel. No pharmacokinetic interaction was found between paclitaxel and cisplatin. After (re-)induction, additional chemotherapy consisted of conventional paclitaxel/cisplatin, paclitaxel/carboplatin, paclitaxel single agent or carboplatin/cyclophosphamide. The overall response rate was 94% in 17 evaluable chemotherapy-nai;ve patients and 84% in 25 patients with recurrent disease. Median progression-free survival (PFS) was 17 months (chemotherapy-nai;ve: 23 months, recurrent: 11 months) and median overall survival was 41 months (chemotherapy-nai;ve: 48 months, recurrent: 24 months). In conclusion, both cisplatin/paclitaxel regimens showed excellent activity with manageable toxicity in patients with advanced ovarian cancer.
authors.affiliation: Department of Medical Oncology, Rotterdam Cancer Institute (Daniel den Hoed Kliniek) and University Hospital Rotterdam, PO Box 5201, The Netherlands.
authors.forename: F E
authors.initials: FE
authors.lastname: de Jongh
authors.forename: R
authors.initials: R
authors.lastname: de Wit
authors.forename: J
authors.initials: J
authors.lastname: Verweij
authors.forename: A
authors.initials: A
authors.lastname: Sparreboom
authors.forename: M J
authors.initials: MJ
authors.lastname: van den Bent
authors.forename: G
authors.initials: G
authors.lastname: Stoter
authors.forename: M E L
authors.initials: ME
authors.lastname: van der Burg
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin