Phase I and pharmacokinetic study of NC-6004, a new platinum entity of cisplatin-conjugated polymer forming micelles

Abstract

2573 Background: NC-6004 contains cisplatin derivatives in micellar nanoparticles. Preclinical activity was seen in platinum resistant cell lines. We report a phase I trial of NC-6004 with doses from 10–120mg/m2 cisplatin equivalent. Methods: NC-6004 dose was escalated in patients with refractory solid tumors according to toxicity with 1 patient per dose level until grade 2 toxicity observed then 3–6 evaluable patients per dose level. Eligible patients had adequate bone marrow, hepatic and renal function. NC-6004 was administered as a 1 hour intravenous infusion on day 1 of a 21 day cycle (C). Patients were monitored for usual dose-limiting toxicities (DLT) and renal function assessed by EDTA GFR. Pharmacokinetics (PK) of cisplatin were characterized by atomic absorption spectrometry for total platinum, micellar component by gel-filtration, inductively-coupled plasma mass spectrometry for free platinum species. Patients were restaged every 2 cycles and treatment continued if clinical benefit and acceptabl...