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Systemic Nanoparticle Paclitaxel ( nab ‐Paclitaxel) for In‐stent Restenosis I (SNAPIST‐I): A First‐in‐Human Safety and Dose‐finding Study

2007; Wiley; Volume: 30; Issue: 4 Linguagem: Inglês

10.1002/clc.20066

1932-8737

James R. Margolis, John W. McDonald, Richard R. Heuser, Peter Klinke, Ron Waksman, Renu Virmani, Neil Desai, David Hilton,

Peripheral Artery Disease Management

Abstract Background Paclitaxel‐eluting stents inhibit restenosis; however, this technology has drawbacks (e.g., stent thrombosis, requirement for long‐term antiplatelet ther‐ apy, and cost—particularly for patients with multivessel disease). Systemic treatment with a novel 130‐nm, albumin‐bound particle form of paclitaxel ( nab ‐paclitaxel) has been shown to reduce restenosis in animals. Hypothesis This study was designed to establish the safety and optimal dose of systemic nab ‐paclitaxel for reducing in‐stent restenosis in humans. If well tolerated, systemic nab ‐paclitaxel may be used with any available bare‐metal stent and at potentially lower cost than drug‐eluting stents. Methods Patients received nab ‐paclitaxel 10, 30, 70, or 100 mg/m 2 intravenously after stenting of a single de novo lesion ≥ 3 mm in diameter. Study endpoints included safety and major adverse cardiac events (MACE) at 2 and 6 months. Results Data were obtained for all 23 enrolled patients (mean age 66 ± 10 years, 74% men, 26% with diabetes). No significant adverse events (AE) were attributable to nab ‐paclitaxel at 10 or 30 mg/m 2 . Moderate neutropenia, moderate sensory neuropathy, and mild to moderate, reversible alopecia occurred only at doses of 70 and 100 mg/m 2 ; therefore, doses of 70 mg/m 2 or higher were considered unacceptable in this patient population. No MACE were reported at 2 months. At 6 months, 4 target lesion revascularizations (TLR) for restenoses were reported (2 each in the 10‐ and 100‐mg/m 2 ‐dose groups). Conclusions Systemic nab ‐paclitaxel was well tolerated at doses below 70 mg/m 2 in this group of patients; no unexpected AE were noted. Additional studies are under way to explore intravenous and intracoronary administration of nab ‐paclitaxel. Copyright © 2007 Wiley Periodicals, Inc.