Ueda Taeko
   Department   School of Medicine  Obstetrics and Gynecology, Clinical Medical Sciences
   Position  
Article types journal article
Language English
Peer review Peer reviewed
Title BK-UM in patients with recurrent ovarian cancer or peritoneal cancer: a first-in-human phase-I study.
Journal Formal name:BMC cancer
Abbreviation:BMC Cancer
ISSN code:14712407/14712407
Volume, Issue, Page 17(1),89頁
Author and coauthor Miyamoto Shingo, Yotsumoto Fusanori, Ueda Taeko, Fukami Tatsuya, Sanui Ayako, Miyata Kohei, Nam Sung Ouk, Fukagawa Satoshi, Katsuta Takahiro, Maehara Miyako, Kondo Haruhiko, Miyahara Daisuke, Shirota Kyoko, Yoshizato Toshiyuki, Kuroki Masahide, Nishikawa Hiroaki, Saku Keijiro, Tsuboi Yoshio, Ishitsuka Kenji, Takamatsu Yasushi, Tamura Kazuo, Matsunaga Akira, Hachisuga Toru, Nishino Shinsuke, Odawara Takashi, Maeda Kazuhiro, Manabe Sadao, Ishikawa Toyokazu, Okuno Yoshinobu, Ohishi Minako, Hikita Tomoya, Mizushima Hiroto, Iwamoto Ryo, Mekada Eisuke
Publication date 2017/01
Summary BACKGROUND:BK-UM (CRM197) is a mutant form of diphtheria toxin and a specific inhibitor of heparin-binding epidermal growth factor-like growth factor (HB-EGF). We assessed the safety, pharmacokinetics, recommended dose, and efficacy of BK-UM in patients with recurrent ovarian cancer (OC) or peritoneal cancer (PC), and measured HB-EGF levels in serum and abdominal fluid after BK-UM administration.METHODS:Eleven patients with advanced or recurrent OC or PC were enrolled and treated with BK-UM via the intraperitoneal route. The dose was escalated (1.0, 2.0, 3.3, and 5.0 mg/m(2)) using a 3 + 3 design.RESULTS:Eight of 11 patients completed treatment. No dose-limiting toxicity (DLT) was experienced at dose levels 1 (1.0 mg/m(2)) and 2 (2.0 mg/m(2)). Grade 3 transient hypotension as an adverse event (defined as a DLT in the present study) was observed in two of four patients at dose level 3 (3.3 mg/m(2)). Treatment with BK-UM was associated with decreases in HB-EGF levels in serum and abdominal fluid in seven of 11 patients and five of eight patients, respectively. Clinical outcomes included a partial response in one patient, stable disease in five patients, and progressive disease in five patients.CONCLUSIONS:BK-UM was well tolerated at doses of 1.0 and 2.0 mg/m(2), with evidence for clinical efficacy in patients with recurrent OC or PC. A dose of 2.0 mg/m(2) BK-UM is recommended for subsequent clinical trials.TRIAL REGISTRATION:This trial was prospectively performed as an investigator-initiated clinical trial. The trial numbers are UMIN000001002 and UMIN000001001, with registration dates of 1/30/2008 and 2/4/2008, respectively. UMIN000001001 was registered as a trial for the continuous administration of BK-UM after UMIN000001002 .
DOI 10.1186/s12885-017-3071-5
PMID 28143428