title: Open-Label Single-Arm Phase II Trial of Sorafenib Therapy with Drug-eluting Bead Transarterial Chemoembolization in Patients with Unresectable Hepatocellular Carcinoma: Clinical Results.
abstract: OBJECTIVE
  To determine the efficacy of combined continuous sorafenib therapy and drug-eluting bead (DEB) transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (HCC).
  
  
  METHODS
  This study was conducted in accordance with the principles of the Declaration of Helsinki, and all patients provided written informed consent prior to enrollment. Inclusion criteria included unresectable HCC, a treatment naïve status, an Eastern Cooperative Oncology Group score of 0-1, and a Child-Pugh score of A-B7. Continuous sorafenib therapy (400 mg twice daily) was started 1 week before the first round of DEB TACE, which was performed in 6-week cycles. Up to four rounds of DEB TACE therapy were allowed on demand within 6 months. The primary end point was safety. Secondary end points were time to progression (TTP), response rate, and overall survival (OS) and were stratified by the Barcelona Clinic Liver Cancer (BCLC) stage and the duration of sorafenib therapy. OS was assessed with Kaplan-Meier estimates, and the Mantel-Cox log-rank test was used to determine differences in survival. A two-sided P value of less than .05 was considered to indicate a significant difference. The study was approved by the Johns Hopkins institutional review board and remained open from March 2009 to January 2012.
  
  
  RESULTS
  Fifty patients--of whom 76% were male, 92% had a Child-Pugh score of A, and 62% had BCLC stage C disease--underwent a median of three cycles of therapy. The 6-month disease control rate (defined as complete response plus partial response plus stable disease) was 94% according to the response evaluation criteria in solid tumors. Median TTP and OS were 13.9 and 20.4 months, respectively, and 81% of toxicities were grades 1-2. There was one death that was possibly treatment related.
  
  
  CONCLUSIONS
  Combined continuous sorafenib therapy and on-demand DEB TACE provided excellent local disease control and did not lead to multiplicative toxicities. Long-term administration of sorafenib therapy in combination with DEB TACE may have a survival benefit in patients with advanced HCC.
authors.affiliation: From the Departments of Medical Oncology (D.P.C.), Interventional Radiology (D.K.R., A.L.F., J.F.H.G.), Surgical Oncology (T.M.P.), and Radiology (I.R.K.), Johns Hopkins University School of Medicine, 1800 Orleans St, Sheikh Zayed Tower, Suite 7203, Baltimore, MD 21287.
authors.forename: David P
authors.initials: DP
authors.lastname: Cosgrove
authors.affiliation: From the Departments of Medical Oncology (D.P.C.), Interventional Radiology (D.K.R., A.L.F., J.F.H.G.), Surgical Oncology (T.M.P.), and Radiology (I.R.K.), Johns Hopkins University School of Medicine, 1800 Orleans St, Sheikh Zayed Tower, Suite 7203, Baltimore, MD 21287.
authors.forename: Diane K
authors.initials: DK
authors.lastname: Reyes
authors.affiliation: From the Departments of Medical Oncology (D.P.C.), Interventional Radiology (D.K.R., A.L.F., J.F.H.G.), Surgical Oncology (T.M.P.), and Radiology (I.R.K.), Johns Hopkins University School of Medicine, 1800 Orleans St, Sheikh Zayed Tower, Suite 7203, Baltimore, MD 21287.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Pawlik
authors.affiliation: From the Departments of Medical Oncology (D.P.C.), Interventional Radiology (D.K.R., A.L.F., J.F.H.G.), Surgical Oncology (T.M.P.), and Radiology (I.R.K.), Johns Hopkins University School of Medicine, 1800 Orleans St, Sheikh Zayed Tower, Suite 7203, Baltimore, MD 21287.
authors.forename: Allen L
authors.initials: AL
authors.lastname: Feng
authors.affiliation: From the Departments of Medical Oncology (D.P.C.), Interventional Radiology (D.K.R., A.L.F., J.F.H.G.), Surgical Oncology (T.M.P.), and Radiology (I.R.K.), Johns Hopkins University School of Medicine, 1800 Orleans St, Sheikh Zayed Tower, Suite 7203, Baltimore, MD 21287.
authors.forename: Ihab R
authors.initials: IR
authors.lastname: Kamel
authors.affiliation: From the Departments of Medical Oncology (D.P.C.), Interventional Radiology (D.K.R., A.L.F., J.F.H.G.), Surgical Oncology (T.M.P.), and Radiology (I.R.K.), Johns Hopkins University School of Medicine, 1800 Orleans St, Sheikh Zayed Tower, Suite 7203, Baltimore, MD 21287.
authors.forename: Jean-François H
authors.initials: JF
authors.lastname: Geschwind
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D003287:Contrast Media; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D000077157:Sorafenib; D015996:Survival Rate; D014057:Tomography, X-Ray Computed
chemical_list: D000970:Antineoplastic Agents; D003287:Contrast Media; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib