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/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/m2had 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.
Department of Breast and Medical Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. hmukai@east.ncc.go.jp.
Hirofumi
H
Mukai
Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, National Cancer Center, Tokyo, Japan.
Ken
K
Kato
Department of Gastrointestinal and Medical Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
Taito
T
Esaki
Department of Breast Surgery, National Hospital Organization Shikoku Cancer Center, Ehime, Japan.
Shouzou
S
Ohsumi
Department of Breast and Endocrine Surgery, University of Tsukuba Hospital, Ibaragi, Japan.
Yasuo
Y
Hozomi
Department of Breast and Medical Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Nobuaki
N
Matsubara
Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, National Cancer Center, Tokyo, Japan.
Tetsuya
T
Hamaguchi
Division of Developmental Therapeutics, National Cancer Center Hospital East, Chiba, Japan.
Yasuhiro
Y
Matsumura
Nippon Kayaku Co., Ltd., Tokyo, Japan.
Rika
R
Goda
Nippon Kayaku Co., Ltd., Tokyo, Japan.
Takayuki
T
Hirai
Nippon Kayaku Co., Ltd., Tokyo, Japan.
Yoshihiro
Y
Nambu
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011379:Prognosis; D015996:Survival Rate; D014018:Tissue Distribution
D000972:Antineoplastic Agents, Phytogenic; C500671:NK105; D017239:Paclitaxel
Breast cancer; DDS; NK105; Paclitaxel; Polymeric micelles