Phase I and pharmacokinetic study of polymeric micelle-formulated paclitaxel in adult Chinese patients with advanced solid tumors

Polymeric micelle-formulated paclitaxel (PM paclitaxel) is a nanoscale drug delivery compound. This study investigated the maximum tolerated dose (MTD), dose-limiting toxicities, and pharmacokinetic (PK) profile of PM paclitaxel in Chinese patients with treatment-refractory advanced or relapsed solid tumors. Dose escalation of PM paclitaxel followed the standard '3 + 3' rule, starting at 175 mg/m(2). PM paclitaxel was administered over 3 h every 3 weeks. Patients were treated until disease progression, intolerance, death, or consent withdrawal. Blood samples were collected for PK testing. All 23 patients were evaluable for toxicity. Neutropenia, neuropathy, and myalgia were the most common toxicities; acute hypersensitivity reaction was not observed. One of six patients at dose level 4 (350 mg/m(2)) and two of six patients at dose level 5 (390 mg/m(2)) developed grade 4 neutropenia. The MTD was 350 mg/m(2). No patients discontinued treatment because of neuropathy. Partial response was seen in five of 20 patients (25 %) who had response assessment, three of whom had prior exposure to taxanes (two were heavily pretreated). Ten patients (50 %) had stable disease at cycle 2 and only five patients (25 %) had disease progression. The area under the curve and the maximum concentration of paclitaxel increased with escalating doses, suggesting that PM paclitaxel has linear PKs. The main dose-limiting toxicity for PM paclitaxel was neutropenia, and the recommended dose for phase II study is 300 mg/m(2). PM paclitaxel is superior to conventional paclitaxel for its simplified premedication regimen and delivery of a higher paclitaxel dose without increased neuropathy.