1. 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.
- Author
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Quach, Hang, White, Darrell, Spencer, Andrew, Ho, P., Bhutani, Divaya, White, Mike, Inamdar, Sandeep, Morris, Chris, Ou, Ying, Gyger, Martin, and Ho, P Joy
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PHARMACOKINETICS , *OLIGOPEPTIDES , *MULTIPLE myeloma , *CHRONIC kidney failure , *DISEASE relapse , *MEDICATION safety , *PATIENTS , *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 ,CHRONIC kidney failure complications - Abstract
Purpose: 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.Methods: 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.Results: 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.Conclusion: 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. [ABSTRACT FROM AUTHOR]- Published
- 2017
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