Dose-dense cisplatin/paclitaxel: a well-tolerated and highly effective chemotherapeutic regimen in patients with advanced ovarian cancer

• Published in: European journal of cancer (1990) 2002-10, Vol.38 (15), p.2005-2013
• Main Authors: de Jongh, F.E, de Wit, R, Verweij, J, Sparreboom, A, van den Bent, M.J, Stoter, G, van der Burg, M.E.L
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Carboplatin - administration & dosage; Carboplatin - adverse effects; Carboplatin - pharmacokinetics; Chemotherapy; Cisplatin; Cisplatin - administration & dosage; Cisplatin - adverse effects; Cisplatin - pharmacokinetics; Disease-Free Survival; Dose intensity; Dose-Response Relationship, Drug; Drug Interactions; Female; Humans; Medical sciences; Middle Aged; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - metabolism; Paclitaxel; Paclitaxel - administration & dosage; Paclitaxel - adverse effects; Paclitaxel - pharmacokinetics; Pharmacokinetics; Pharmacology. Drug treatments; Response; Toxicity; Weekly chemotherapy
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/S0959-8049(02)00242-3

A randomised phase I/II trial with weekly cisplatin 70 mg/m2 (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-naı̈ve or had a first relapse after platinum-based chemotherapy. Paclitaxel could be safely escalated to 225 mg/m2 4-weekly or 100 mg/m2 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-naı̈ve patients and 84% in 25 patients with recurrent disease. Median progression-free survival (PFS) was 17 months (chemotherapy-naı̈ve: 23 months, recurrent: 11 months) and median overall survival was 41 months (chemotherapy-naı̈ve: 48 months, recurrent: 24 months). In conclusion, both cisplatin/paclitaxel regimens showed excellent activity with manageable toxicity in patients with advanced ovarian cancer.