title: HATT: a phase IV, single-arm, open-label study of sorafenib in Taiwanese patients with advanced hepatocellular carcinoma.
abstract: BACKGROUND
  Sorafenib significantly improves survival in patients with advanced hepatocellular carcinoma (HCC). This phase IV study assessed sorafenib efficacy/safety in Taiwanese patients with advanced HCC and Child-Pugh A status.
  
  
  METHODS
  All patients received 400 mg sorafenib BID. Safety, efficacy, sorafenib pharmacokinetics, and Child-Pugh progression were evaluated. A hand-foot skin reaction (HFSR) prevention substudy assessed HFSR incidence and grade/severity and time to HFSR in 29 and 34 patients randomized to corticosteroid and noncorticosteroid ointments, respectively, and in 88 nonrandomized patients.
  
  
  RESULTS
  The 151 patients included 120 (80%) male patients and 81 (54%) with stage IV disease. Mean sorafenib dose was 626 mg/day, and median treatment duration was 4.2 months. Median overall survival (OS), progression-free survival, and time to progression (TTP) were 8.6, 2.7, and 3.8 months, respectively. Disease control and response rates (partial responses only) were 48 and 6.6%, respectively. Median TTP from Child-Pugh A to B/C was 88 days. Drug-related adverse events (AEs) occurred in 89.4% of patients; none were new or unexpected. The most frequent grade ≥3 drug-related, treatment-emergent AEs were HFSR (13.2%), diarrhea (11.9%), and hypertension (6.6%). Corticosteroid ointment tended to reduce the severity and incidence of all HFSR-associated parameters. Pharmacokinetic exposure was unaltered by Child-Pugh progression. The final pharmacokinetic model predicted 13.1 and 33.8% reductions in sorafenib exposure over 6 and 12 months, respectively.
  
  
  CONCLUSIONS
  There was a trend of longer OS and TTP in Taiwanese patients with advanced HCC compared with patients with advanced HCC in the Asia-Pacific trial. Sorafenib exposure did not correlate with liver function. Reduced pharmacokinetic exposure over time was unrelated to reduced or interrupted dosing.
authors.affiliation: Division of Hepatology, Department of Gastroenterology and Hepatology, Linkou and Taipei Chang Gung Memorial Hospital Chang Gung University, No. 5 Fuhsing Street, Kuei Shan Hsiang, Taoyuan, Taiwan. lsmpaicyto@gmail.com.
authors.forename: Shi-Ming
authors.initials: SM
authors.lastname: Lin
authors.affiliation: Division of Hepato-Gastroenterology, Kaohsiung Chang Gung Memorial Hospital, 100 Tapei Road, Niaosung, Kaohsiung, 833, Taiwan.
authors.forename: Sheng-Nan
authors.initials: SN
authors.lastname: Lu
authors.affiliation: The Division of Hematology & Oncology, Chiayi Chang Gung Memorial Hospital, 6 W Sec, Chia Pu Road, Pu-Tz City, 613, Chiayi, Taiwan.
authors.forename: Ping-Tsung
authors.initials: PT
authors.lastname: Chen
authors.affiliation: Organ Transplantation Center, China Medical University Hospital, North District, Taichung City, 404, Taiwan.
authors.forename: Long-Bin
authors.initials: LB
authors.lastname: Jeng
authors.affiliation: Division of Hepato-Biliary-Pancreatic Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan.
authors.forename: Shinn-Cherng
authors.initials: SC
authors.lastname: Chen
authors.affiliation: Division of Hepato-Gastroenterology, Buddhist Tzu Chi General Hospital, Tzu Chi University, No. 707, Sec. 3 Chung Yang Road, Hualian City, 970, Hualien County, Taiwan.
authors.forename: Chi-Tan
authors.initials: CT
authors.lastname: Hu
authors.affiliation: Liver Center, Cathay General Hospital, Taipei and Medical Faculty, Fu-Jen Catholic University, No. 280, Sec. 4 Jen-Ai Road, Taipei, 10630, Taiwan.
authors.forename: Sien-Sing
authors.initials: SS
authors.lastname: Yang
authors.affiliation: Clinical Statistics, Bayer HealthCare Pharmaceuticals, Medical Affairs, Building C2 1.11, 220 Ave de la Recherche, Loos, 59120, France.
authors.forename: Marie-Aude
authors.initials: MA
authors.lastname: Le Berre
authors.affiliation: Global Clinical Development, Bayer HealthCare Co. Ltd., 18F Tower B, Bayer Center, No. 27, Dong San Huan North Road, Chaoyang District, Beijing, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Mitchell Pharmaceutical Consulting, 1188 Hawk Ridge Road, Lafayette, CO, 80026, USA.
authors.forename: David Y
authors.initials: DY
authors.lastname: Mitchell
authors.affiliation: qPharmetra, LLC, Kwakkenbergweg 39, 6523, MK, Nijmegen, The Netherlands.
authors.forename: Klaas
authors.initials: K
authors.lastname: Prins
authors.affiliation: BAST Inc Limited, 7 Wellingtonia Close, Shepshed, LE12 9FB, UK.
authors.forename: Joachim
authors.initials: J
authors.lastname: Grevel
authors.affiliation: Clinical Sciences, Bayer Healthcare Pharmaceuticals, 100 Bayer Road, Whippany, NJ, USA.
authors.forename: Carol A E
authors.initials: CA
authors.lastname: Peña
authors.affiliation: Global Clinical Development Oncology, Bayer Healthcare Pharmaceuticals, 100 Bayer Road, Whippany, NJ, USA.
authors.forename: Gerold
authors.initials: G
authors.lastname: Meinhardt
mesh_terms: D000287:Administration, Topical; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D018572:Disease-Free Survival; D005260:Female; D060831:Hand-Foot Syndrome / Q000188:drug therapy / Q000209:etiology; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009824:Ointments; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D000077157:Sorafenib; D013624:Taiwan
chemical_list: D000305:Adrenal Cortex Hormones; D000970:Antineoplastic Agents; D009824:Ointments; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib
keywords: Advanced hepatocellular carcinoma; Metastatic hepatocellular carcinoma; Overall survival; Sorafenib; Taiwanese patients; Time to progression