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- Title
Pharmacokinetics and safety of carfilzomib in patients with relapsed multiple myeloma and end-stage renal disease (ESRD): an open-label, single-arm, phase I study.
- Authors
Quach, Hang; White, Darrell; Spencer, Andrew; Ho, P.; Bhutani, Divaya; White, Mike; Inamdar, Sandeep; Morris, Chris; Ou, Ying; Gyger, Martin; Ho, P Joy
- Abstract
<bold>Purpose: </bold>The pharmacokinetics (PK) of carfilzomib have been previously studied in multiple myeloma patients with varying degrees of renal impairment (normal, mild, moderate, severe, and end-stage renal disease [ESRD]) at doses of 15 and 20 mg/m2. This study evaluated carfilzomib PK at higher doses of 27 and 56 mg/m2 in normal renal function and ESRD patients.<bold>Methods: </bold>Patients received carfilzomib on two consecutive days/week for 3 weeks every 28-day cycle: 20 mg/m2 (cycle 1 day 1-2), escalated to 27 mg/m2 on cycle 1 day 8; if tolerated, 56 mg/m2 starting cycle 2 day 1. The primary objective was PK assessment with safety/tolerability and response rate as secondary and exploratory objectives, respectively.<bold>Results: </bold>26 patients were enrolled (15 normal, 11 ESRD). There was a trend toward higher area under the concentration time curve (AUC) and maximum concentration in ESRD versus normal renal function patients; however, high interpatient PK variability was discerned. Relative to patients with normal renal function, ESRD patients showed 33% higher AUC. Overall response rate was 43% for the normal renal function and 60% for the ESRD groups. Safety findings were generally similar between the two groups and consistent with the known safety profile of carfilzomib in multiple myeloma patients.<bold>Conclusion: </bold>There were no meaningful differences in PK between patients with normal renal function and ESRD in light of carfilzomib exposure-response relationships. These results continue to support dosing recommendation that no starting dose adjustment of carfilzomib appears warranted in patients with baseline renal impairment.
- Subjects
PHARMACOKINETICS; OLIGOPEPTIDES; MULTIPLE myeloma; CHRONIC kidney failure; DISEASE relapse; MEDICATION safety; PATIENTS; CHRONIC kidney failure complications; ANTINEOPLASTIC agents; BIOTRANSFORMATION (Metabolism); CLINICAL trials; COMPARATIVE studies; DOSE-effect relationship in pharmacology; HEMODIALYSIS; KIDNEY function tests; RESEARCH methodology; MEDICAL cooperation; RESEARCH; EVALUATION research; TREATMENT effectiveness; DISEASE complications; THERAPEUTICS
- Publication
Cancer Chemotherapy & Pharmacology, 2017, Vol 79, Issue 6, p1067
- ISSN
0344-5704
- Publication type
journal article
- DOI
10.1007/s00280-017-3287-8