Systemic nanoparticle paclitaxel (nab-paclitaxel) for in-stent restenosis I (SNAPIST-I): a first-in-human safety and dose-finding study.
BACKGROUND
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.


OBJECTIVE
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 >or= 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.
Margolis
James
J
Miami International Cardiology Consultants, Miami, Florida, USA.
McDonald
John
J
Heuser
Richard
R
Klinke
Peter
P
Waksman
Ron
R
Virmani
Renu
R
Desai
Neil
N
Hilton
David
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019917:Blood Vessel Prosthesis Implantation / Q000295:instrumentation; D002317:Cardiovascular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000601:surgery; D023903:Coronary Restenosis / Q000000981:diagnostic imaging / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D053758:Nanoparticles; D017239:Paclitaxel / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D015607:Stents / Q000009:adverse effects*; D013997:Time Factors; D016896:Treatment Outcome
D002317:Cardiovascular Agents; D017239:Paclitaxel