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Pharmacokinetic study of bortezomib administered intravenously in Taiwanese patients with multiple myeloma
Author(s) -
Huang ShangYi,
Chang ChengShyong,
Liu TaChih,
Wang PoNan,
Yeh SuPeng,
Ho ChingLiang,
Kuo MingChung,
Lin HsuanYu,
Jong Jan,
Chen JiaYi,
Yang YaWen
Publication year - 2018
Publication title -
hematological oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 44
eISSN - 1099-1069
pISSN - 0278-0232
DOI - 10.1002/hon.2432
Subject(s) - medicine , pharmacokinetics , neutropenia , bortezomib , multiple myeloma , leukopenia , volume of distribution , adverse effect , gastroenterology , regimen , toxicity
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.