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

Abstract

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/m2; n = 16). At a dose level of 100 mg/m2, 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/m2 had a dose reduction, while a dose delay occurred in two. NK105 exhibited linear pharmacokinetics at doses of 50-100 mg/m2, and approximately 5 % of total paclitaxel was released from micelles. Thus, the recommended dose was set at 80 mg/m2, 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.

• Authors: Hirofumi Mukai, Ken Kato, Taito Esaki, Shouzou Ohsumi, Yasuo Hozomi, Nobuaki Matsubara, Tetsuya Hamaguchi, Yasuhiro Matsumura, Rika Goda, Takayuki Hirai, Yoshihiro Nambu
• Journal: Investigational new drugs (Invest New Drugs) Vol. 34 Issue 6 Pg. 750-759 (12 2016) ISSN: 1573-0646 [Electronic] United States
• PMID: 27595901 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• NK105
• Paclitaxel

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents, Phytogenic (pharmacokinetics, therapeutic use)
• Drug Administration Schedule
• Female
• Follow-Up Studies
• Humans
• Male
• Maximum Tolerated Dose
• Middle Aged
• Neoplasm Staging
• Neoplasms (drug therapy, pathology)
• Paclitaxel (analogs & derivatives, pharmacokinetics, therapeutic use)
• Prognosis
• Survival Rate
• Tissue Distribution