Phase I study of NK105, a nanomicellar paclitaxel formulation, administered on a weekly schedule in patients with solid tumors.

Previous studies have established the rationale for NK105, a nanomicellar formulation of paclitaxel, administered every 3 weeks. The aim of this phase I study was to determine the recommended dose and pharmacokinetics of weekly administered NK105. NK105 was administered by a 30-min infusion once weekly for three consecutive weeks in each 4-week cycle. In the dose-escalation phase, three to seven patients with solid tumors were enrolled to each of the four dose levels (50-100 mg/m ² ; n = 16). At a dose level of 100 mg/m ² , predefined dose-limiting toxicity (DLT) manifested in only one out of six evaluable patients, whereas a dose delay due to neutropenia during the first course occurred two patients. None of the three patients given 80 mg/m ² had a dose reduction, while a dose delay occurred in two. NK105 exhibited linear pharmacokinetics at doses of 50-100 mg/m ² , and approximately 5 % of total paclitaxel was released from micelles. Thus, the recommended dose was set at 80 mg/m ² , and an additional 10 advanced breast cancer (ABC) patients were given this dose in the dose-expansion phase. DLT manifested in two patients, and grade ≥ 3 neutropenia was found in eight patients. Among the nine patients who completed the first cycle, four had a dose reduction, mostly because of neutropenia. Of the 10 patients, six achieved partial response (PR), and four achieved stable disease (SD) status. Overall, weekly NK105 was well tolerated and had a desirable antitumor activity profile. Further investigations of NK105 in ABC patients are currently underway.
Competing Interests: Compliance with ethical standards Funding The study was designed and funded by Nippon Kayaku Co., Ltd. NK105 was provided by Nippon Kayaku. Nippon Kayaku collected and analyzed the data and contributed to the interpretation of the results. Disclosure of Potential Conflict of Interest Yasuhiro Matsumura received consigned research funding from Nippon Kayaku. Rika Goda, Takayuki Hirai, and Yoshihiro Nambu are employees of Nippon Kayaku. The other authors have no conflict of interest. Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee as well as with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was conducted in compliance with the International Conference on Harmonization of Good Clinical Practice Guidelines. Before the initiation of the study, the protocol had been reviewed and approved by the institutional review board of each institution. Informed consent Informed consent was obtained from all individual participants included in the study.