Phase I study of NK105, a nanomicellar paclitaxel formulation, administered on a weekly schedule in patients with solid tumors
| Autor: | Takayuki Hirai, Tetsuya Hamaguchi, Taito Esaki, Hirofumi Mukai, Yoshihiro Nambu, Ken Kato, Rika Goda, Shouzou Ohsumi, Yasuo Hozomi, Yasuhiro Matsumura, Nobuaki Matsubara |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty Maximum Tolerated Dose Paclitaxel Neutropenia Gastroenterology Drug Administration Schedule DDS 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Breast cancer Pharmacokinetics Internal medicine Neoplasms Phase I Studies medicine Humans Pharmacology (medical) Tissue Distribution Survival rate Aged Neoplasm Staging Pharmacology Aged 80 and over business.industry Cancer Middle Aged medicine.disease Prognosis NK105 Antineoplastic Agents Phytogenic Surgery Phase i study Survival Rate 030104 developmental biology chemistry Oncology 030220 oncology & carcinogenesis Toxicity Polymeric micelles Female business Follow-Up Studies |
| Zdroj: | Investigational New Drugs |
| ISSN: | 1573-0646 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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