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-naïve 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-naïve patients and 84% in 25 patients with recurrent disease. Median progression-free survival (PFS) was 17 months (chemotherapy-naïve: 23 months, recurrent: 11 months) and median overall survival was 41 months (chemotherapy-naïve: 48 months, recurrent: 24 months). In conclusion, both cisplatin/paclitaxel regimens showed excellent activity with manageable toxicity in patients with advanced ovarian cancer.

Cisplatin, Dose intensity, Ovarian cancer, Paclitaxel, Pharmacokinetics, Response, Toxicity, Weekly chemotherapy
dx.doi.org/10.1016/S0959-8049(02)00242-3, hdl.handle.net/1765/68100
European Journal of Cancer
Department of Neurology

de Jongh, F.E, de Wit, R, Verweij, J, Sparreboom, A, van den Bent, M.J, Stoter, G, & van der Burg, M.E.L. (2002). Dose-dense cisplatin/paclitaxel: A well-tolerated and highly effective chemotherapeutic regimen in patients with advanced ovarian cancer. European Journal of Cancer, 38(15), 2005–2013. doi:10.1016/S0959-8049(02)00242-3