title: A phase 1 study of lenvatinib, multiple receptor tyrosine kinase inhibitor, in Japanese patients with advanced solid tumors.
abstract: OBJECTIVE
  This phase 1 study aimed to assess the tolerability, safety, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of lenvatinib capsules in Japanese patients with solid tumors when administered orally up to 24 mg on a once-daily (QD) continuous schedule.
  
  
  METHODS
  Patients were enrolled in one of the two sequential cohorts (20 or 24 mg) of lenvatinib on a 28-day cycle based on the conventional 3 + 3 dose escalation design. Adverse events (AEs) were graded using the Common Terminology Criteria for Adverse Events, version 4.0. Tolerability was judged based on dose-limiting toxicities (DLTs) during Cycle 1. The drug was defined as tolerable when the incidence of DLTs was less than 33 %.
  
  
  RESULTS
  Nine patients received lenvatinib [20 mg (n = 3); 24 mg (n = 6)]. No DLTs were observed. The most common AEs were thrombocytopenia, blood thyroid stimulating hormone increased, and hypertension (89 %), followed by leukopenia, headache, and proteinuria (78 %). The area under the concentration-time curve and maximum observed concentration increased dose proportionally. The PK profiles were similar to those in non-Japanese phase 1 studies. One patient with leiomyosarcoma showed a partial response, and three patients have maintained stable disease for more than 6 months.
  
  
  CONCLUSIONS
  The 24-mg QD continuous dose of lenvatinib was determined to be tolerable with encouraging anti-tumor activity in Japanese patients with solid tumors.
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Nakamichi
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nokihara
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Department of Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Honda
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Tamura
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wakui
authors.affiliation: Clinical Development, Eisai Co., Ltd., Tokyo, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Clinical Development, Eisai Co., Ltd., Tokyo, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Yusa
authors.affiliation: Biostatistics, Eisai Co., Ltd., Tokyo, Japan.
authors.forename: Katsuki
authors.initials: K
authors.lastname: Fujino
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. tamuratomohide@gmail.com.|St. Luke's International Hospital, Akashi-cho 9-1, Chuo-ku, Tokyo, 104-8560, Japan. tamuratomohide@gmail.com.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tamura
mesh_terms: D000328:Adult; D019540:Area Under Curve; D044466:Asian People; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007564:Japan; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009369:Neoplasms / Q000188:drug therapy* / Q000208:ethnology / Q000378:metabolism*; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000493:pharmacokinetics*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics; D011804:Quinolines / Q000009:adverse effects / Q000493:pharmacokinetics*; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011804:Quinolines; C531958:lenvatinib
keywords: Angiogenesis; E7080; Japanese; Lenvatinib; Phase 1; Safety