title: Megestrol and embryonic extracts in the treatment of advanced hepatocellular carcinoma: A prospective randomized trial in the pre-sorafenib era.
abstract: BACKGROUND
  Patients with advanced hepatocellular carcinoma (HCC) achieved significant results by the new treatment with sorafenib (a multi-tyrosine kinase inhibitor), but, because it has been tested mainly in Child A cirrhosis, patients with impaired liver function are not eligible for the treatment.
  
  
  METHODS
  This study was an open label phase III randomized trial comparing Synchro-Levels (Alphrema, Varese, Italy) and megestrol, with a 2:1 design, in patients with advanced HCC, planned before the sorafenib registration. End-points were objective response and impact on performance status (primary) and biochemical response (secondary).
  
  
  RESULTS
  The patients enrolled were 61 (43 men, 18 women; Child A in 28 [48%] and B in 33 [52%]). Forty-three were assigned to Synchro-Levels, 18 to megestrol. Most patients had multifocal disease (75% in megestrol and 59% in Synchro-Levels) and there was a significant difference in tumor burden, with more advanced disease in the megestrol arm (P = 0.0002). At 3 months, tumor burden was more frequently stable with megestrol, while performance status was significantly better in patients treated with Synchro-Levels. At 6 months, alpha-fetoprotein was more frequently stable or reduced with megestrol. An objective response was observed in a megestrol-treated patient. Mortality was significantly lower and long-term survival significantly more frequent with megestrol.
  
  
  CONCLUSIONS
  Megestrol treatment shows good results in advanced HCC and could become part of best supportive care in patients not suitable for other treatments, that, despite sorafenib, remain an important share.
authors.affiliation: Department of Surgical and Gastroenterological Sciences, Padua University, Via Giustiniani,Padua, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Giacomin
authors.forename: Adriana
authors.initials: A
authors.lastname: Sergio
authors.forename: Veronica
authors.initials: V
authors.lastname: Vanin
authors.forename: Pietro
authors.initials: P
authors.lastname: Tartaro
authors.forename: Daniela
authors.initials: D
authors.lastname: Paccagnella
authors.forename: Mauro
authors.initials: M
authors.lastname: Mazzucco
authors.forename: Fabio
authors.initials: F
authors.lastname: Farinati