Evaluation of oral versus intravenous dose of vinorelbine to achieve equivalent blood exposures in patients with solid tumours

摘要: Patient’s preference is for oral chemotherapy when both and i.v. are available, provided that efficacy equivalent. Reliable switch from to possible if correspondence between respective doses has been established. Vinorelbine was developed as a line extension of VRL on the basis similar AUCs result in activities. From first crossover study 24 patients receiving 25 mg/m2 80 data extrapolation concluded bioequivalence 30 oral. A new trial performed support this calculation. In design (PS 0-1) with advanced solid tumours (44% breast carcinoma), administered (30 i.v., oral) standard meal 5-HT3 antagonists, at 2 weeks interval. Pharmacokinetics over 168 h measured by LC-MS/MS. Statistics included tests. Forty-eight were evaluable PK: median age 58 years (25–71), PS0/PS1: 20/28, M/F: 11/37. Mean 1,230 ± 290 1,216 521 ng/ml oral, respectively. The confidence interval AUC ratio (0.83–1.03) within required regulatory range (0.8–1.25) proved two doses. absolute bioavailability 37.8 16.0%, close value (40%). Patient tolerability globally comparable forms no significant difference either haematological or non-haematological toxicities (grade 3–4). This study, conducted larger population, confirmed reliable dose previously established vinorelbine