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

Abstract

Paclitaxel-eluting stents inhibit restenosis; however, this technology has drawbacks (e.g., stent thrombosis, requirement for long-term antiplatelet therapy, 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. 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. Patients received nab-paclitaxel 10, 30, 70, or 100 mg/m(2) intravenously after stenting of a single de novo lesion >or= 3 mm in diameter. Study endpoints included safety and major adverse cardiac events (MACE) at 2 and 6 months. 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). 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.