Dose-escalating and pharmacological study of bortezomib in adult cancer patients with impaired renal function: a National Cancer Institute Organ Dysfunction Working Group Study

Purpose To determine the toxicities, pharmacokinetics, pharmacodynamics, and maximum tolerated dose of bortezomib in patients with renal impairment and to develop dosing guidelines for such a patient population. Patients and Methods Sixty-two adult cancer patients received intravenous bortezomib at 0.7–1.5 mg/m 2 on days 1, 4, 8, and 11 every 3 weeks. Patients were stratified by 24-h creatinine clearance (CrCl) normalized to body surface area (BSA) 1.73 m 2 into five cohorts: normal renal function (≥60 ml/min/1.73 m 2 ); mild dysfunction (40–59 ml/min/1.73 m 2 ); moderate dysfunction (20–39 ml/min/1.73 m 2 ); severe dysfunction (