title: Phase 2 study of lenvatinib in patients with advanced hepatocellular carcinoma.
abstract: BACKGROUND
  Lenvatinib is an oral inhibitor of vascular endothelial growth factor receptor 1-3, fibroblast growth factor receptor 1-4, platelet-derived growth factor receptor alpha, RET, and KIT. This phase 2, single-arm, open-label multicenter study evaluated lenvatinib in advanced hepatocellular carcinoma (HCC).
  
  
  METHODS
  Patients with histologically/clinically confirmed advanced HCC who did not qualify for surgical resection or local therapies received lenvatinib at a dosage of 12 mg once daily (QD) in 28-day cycles. The primary efficacy endpoint was time to progression (TTP) per modified Response Evaluation Criteria in Solid Tumors v1.1; secondary efficacy endpoints included objective response rate (ORR), disease control rate (DCR), and overall survival (OS).
  
  
  RESULTS
  Between July 2010 and June 2011, 46 patients received lenvatinib at sites across Japan and Korea. The median TTP, as determined by independent radiological review, was 7.4 months [95 % confidence interval (CI): 5.5-9.4]. Seventeen patients (37 %) had partial response and 19 patients (41 %) had stable disease (ORR: 37 %; DCR: 78 %). Median OS was 18.7 months (95 % CI: 12.7-25.1). The most common any-grade adverse events (AEs) were hypertension (76 %), palmar-plantar erythrodysesthesia syndrome (65 %), decreased appetite (61 %), and proteinuria (61 %). Dose reductions and discontinuations due to AEs occurred in 34 (74 %) and 10 patients (22 %), respectively. Median body weight was lower in patients with an early (<30 days) dose withdrawal or reduction than in those without.
  
  
  CONCLUSIONS
  Lenvatinib 12-mg QD showed clinical activity and acceptable toxicity profiles in patients with advanced HCC, but early dose modification was necessary in patients with lower body weight. Further development of lenvatinib in HCC should consider dose modification by body weight. TRIAL REGISTRATION ID: www.ClinicalTrials.gov NCT00946153.
authors.affiliation: Department of Hepatology, Toranomon Hospital, Toranomon 2-2-2, Minato-ku, Tokyo, 105-8470, Japan. ikedakenji@tora.email.ne.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Ikeda
authors.affiliation: Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Osaka, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kudo
authors.affiliation: Department of Hepatobiliary and Pancreatology, Saga-Ken Medical Centre KOSEIKAN, Saga, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Kawazoe
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Osaka, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Osaki
authors.affiliation: Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Okusaka
authors.affiliation: Eisai Co., Ltd.,, Tokyo, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Tamai
authors.affiliation: Eisai Co., Ltd.,, Tokyo, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Eisai Co., Ltd.,, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hisai
authors.affiliation: Eisai Co., Ltd.,, Tokyo, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Hayato
authors.affiliation: Shunan Memorial Hospital, Yamaguchi, Japan.
authors.forename: Kiwamu
authors.initials: K
authors.lastname: Okita
authors.affiliation: Department of Hepatology, Toranomon Hospital, Toranomon 2-2-2, Minato-ku, Tokyo, 105-8470, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001835:Body Weight; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011804:Quinolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011804:Quinolines; C531958:lenvatinib
keywords: E7080; Hepatocellular carcinoma; Lenvatinib; Tyrosine kinase inhibitor; Vascular endothelial growth factor inhibitor