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BMC Cancer. 2017 Jan 31;17(1):89. doi: 10.1186/s12885-017-3071-5.

BK-UM in patients with recurrent ovarian cancer or peritoneal cancer: a first-in-human phase-I study.

Author information

1
Department of Obstetrics and Gynecology, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan. smiya@cis.fukuoka-u.ac.jp.
2
Center for Advanced Molecular Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan. smiya@cis.fukuoka-u.ac.jp.
3
Department of Obstetrics and Gynecology, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
4
Center for Advanced Molecular Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
5
Department of Obstetrics and Gynecology, University of Occupational and Environmental Health School of Medicine, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
6
Department of Obstetrics and Gynecology, School of Medicine, Kurume University, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
7
Department of Biochemistry, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
8
Department of Cardiology, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
9
Department of Neurology, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
10
Department of Hematology and Immunology, Kagoshima University Medical and Dental Hospital, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan.
11
Department of Internal Medicine, Division of Medical Oncology, Hematology and Infectious Disease, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
12
Department of Laboratory Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
13
Kanonji Institute, Research Foundation for Microbial Diseases of Osaka University, 2-9-41 Yahata-Cho, Kanonji, Kagawa, 768-0061, Japan.
14
Department of Cell Biology, Research Institute for Microbial Disease, Osaka University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
15
Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.

Abstract

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/m2) 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/m2) and 2 (2.0 mg/m2). 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/m2). 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/m2, with evidence for clinical efficacy in patients with recurrent OC or PC. A dose of 2.0 mg/m2 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 .

KEYWORDS:

BK-UM; HB-EGF; Ovarian cancer; Phase-I study; Targeted therapy

PMID:
28143428
PMCID:
PMC5286856
DOI:
10.1186/s12885-017-3071-5
[Indexed for MEDLINE]
Free PMC Article

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