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 aeyen 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.
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- DOI : 10.1007/s10637-016-0381-4
- ISSN : 0167-6997
- eISSN : 1573-0646
- PubMed ID : 27595901
- Web of Science ID : WOS:000387584100009