title: A phase II randomized dose escalation trial of sorafenib in patients with advanced hepatocellular carcinoma.
abstract: BACKGROUND
  Sorafenib has proven survival benefits in patients with advanced hepatocellular carcinoma (HCC). The viability of continuing sorafenib at a higher dosage in patients who experienced radiologic disease progression was investigated.
  
  
  METHODS
  Patients who experienced disease progression while on sorafenib 400 mg twice daily were randomized to sorafenib 600 mg twice daily (n = 49) or best supportive care (n = 52). The primary end point was progression-free survival (PFS). Time to progression, overall survival, and safety were also evaluated.
  
  
  RESULTS
  The study did not meet its primary end point. The difference in PFS between the sorafenib arm (3.91 months) and the best supportive care arm (2.69 months) did not reach statistical significance (p = 0.086). Adverse events were mainly grade 1-2 and similar across both groups. In the sorafenib arm, the most frequent events were diarrhea (80%), weight loss (75%), fatigue (67%), hand-foot-skin reaction (49%), abdominal pain (37%), and stomatitis (26%).
  
  
  CONCLUSIONS
  Escalated-dose sorafenib in patients with advanced HCC who progressed while on sorafenib, failed to provide any clinical benefit. Second-line treatment still remains an open issue to be explored in appropriate clinical trials.
authors.affiliation: Medical Oncology and Hematology Unit, Cancer Center, Humanitas Clinical and Research Center, Rozzano, Milan, Italy. lorenza.rimassa@cancercenter.humanitas.it
authors.forename: Lorenza
authors.initials: L
authors.lastname: Rimassa
authors.forename: Tiziana
authors.initials: T
authors.lastname: Pressiani
authors.forename: Corrado
authors.initials: C
authors.lastname: Boni
authors.forename: Carlo
authors.initials: C
authors.lastname: Carnaghi
authors.forename: Elena
authors.initials: E
authors.lastname: Rota Caremoli
authors.forename: Stefano
authors.initials: S
authors.lastname: Fagiuoli
authors.forename: Paolo
authors.initials: P
authors.lastname: Foa
authors.forename: Stefania
authors.initials: S
authors.lastname: Salvagni
authors.forename: Enrico
authors.initials: E
authors.lastname: Cortesi
authors.forename: Maria
authors.initials: M
authors.lastname: Chiara Tronconi
authors.forename: Nicola
authors.initials: N
authors.lastname: Personeni
authors.forename: Silvia
authors.initials: S
authors.lastname: Bozzarelli
authors.forename: Maria
authors.initials: M
authors.lastname: Chiara Banzi
authors.forename: Silvia
authors.initials: S
authors.lastname: Fanello
authors.forename: Fabio
authors.initials: F
authors.lastname: Romano Lutman
authors.forename: Laura
authors.initials: L
authors.lastname: Giordano
authors.forename: Armando
authors.initials: A
authors.lastname: Santoro
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D009536:Niacinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D010671:Phenylurea Compounds / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000077157:Sorafenib
chemical_list: D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib