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

PURPOSE: 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.

METHODS

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.

RESULTS

A ll 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.

CONCLUSIONS

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.