Pharmacokinetic study of bortezomib administered intravenously in Taiwanese patients with multiple myeloma

摘要

Abstract This phase 4, single‐arm, non‐randomized, open‐label, post?approval commitment study evaluated the pharmacokinetics and safety of bortezomib in Taiwanese patients with multiple myeloma. Patients (≥20?years) with measurable secretory multiple myeloma (serum monoclonal IgG ≥10, IgA/IgE ≥5, IgD ≥0.5?g/L, IgM present [regardless of level], and urine M protein of ≥200?mg/24?h) received intravenous bortezomib 1.3?mg/m 2 , twice weekly for 2?weeks, followed by a 10‐day resting phase (days 12 to 21). Pharmacokinetics and safety were assessed at pre‐specified time points. All enrolled patients (n?=?18, men: 11; women: 7) completed the study. Mean (SD) C max (maximum observed plasma concentration) on day 11 was 266 (77.5) ng/mL, approximately 60% higher compared with non‐Asian patients receiving a similar bortezomib regimen but with overlapping ranges. Because of the protracted terminal phase, half‐life (t 1/2 ), area under the plasma concentration‐time curve from time 0 to infinity (AUC ∞ ), volume of distribution (V z ), and systemic clearance were not assessable. All patients experienced treatment‐emergent adverse events (TEAEs); 78% were drug‐related. Most commonly reported TEAEs were thrombocytopenia (n?=?11 [61%]), neutropenia (n?=?9 [50%]), leukopenia (n?=?6 [33%]), and diarrhoea (n?=?6 [33%]); the most common serious adverse event was pneumonia (n?=?2 [11%]). One patient had a dose reduction due to a TEAE of thrombocytopenia. Overall, bortezomib exposure (AUC) in Taiwanese patients (AUC last [SD]: 230 [147]?ng·h/mL) with twice weekly intravenous administration was comparable with non‐Asian population (AUC last [SD]: 241 [82]?ng·h/mL). Bortezomib treatment was associated with manageable toxicity profile and did not limit the continuity of therapy.