Proven bioequivalence of blood exposure between vinorelbine 80 mg/m2 oral and 30 mg/m2 IV doses in cancer patients

Abstract

2028 Background: Patient’s preference is for oral chemotherapy when both oral and IV are available, provided that efficacy is equivalent. Reliable switch from oral to IV is possible if correspondence between respective doses has been established. Vinorelbine (VRL) oral was developed as a line extension of VRL IV on the basis that similar AUCs result in similar activities. From a first cross-over study on 24 patients receiving VRL 25 mg/m2 IV and 80 mg/m2 oral [Marty et al., Ann Oncol 12(11): 1643–1649, 2001] data extrapolation concluded on AUCs bioequivalence between VRL 30 mg/m2 IV and 80 mg/m2 oral. A new trial was performed to support this calculation. Methods: In a cross-over design study on patients (PS 0–1) with advanced solid tumours (44% breast carcinoma), VRL was administered (30 mg/m2 IV, 80 mg/m2 oral) with a standard meal and 5-HT3 antagonists, at 2 weeks interval. Pharmacokinetics (PK) was performed over 168 h and VRL was measured by LC-MS/MS. Statistics included bioequivalence tests. Results: 48 patients were evaluable for PK: median age 58 y [25 - 71], PS0/PS1: 20/28, M/F: 11/37. Mean AUCs were 1230 ± 290 and 1216 ± 521 ng/ml for IV and oral, respectively. The confidence interval of the AUC ratio [0.83 - 1.03] was within the required regulatory range [0.8 - 1.25] and proved the bioequivalence between the two doses. The absolute bioavailability was 37.8 ± 16.0%, and close to the value from the first study (40%). Patient tolerability was globally comparable between both forms with no significant difference on either haematological or non-haematological toxicities (grade 3–4). Conclusions: The dose correspondence between VRL 80 mg/m2 oral and 30 mg/m2 IV was confirmed in this new study on a larger population, a longer period of blood sampling, and a more sensitive analytical Method: No significant financial relationships to disclose.