title: Long-term results of sorafenib in advanced-stage hepatocellular carcinoma: what can we learn from routine clinical practice?
abstract: OBJECTIVE
  Prospective randomized trials have proven that sorafenib is a valid treatment option for patients with advanced-stage hepatocellular carcinoma (HCC). The aim of the present study is to evaluate the effectiveness and safety of sorafenib in patients encountered in routine clinical practice.
  
  
  METHODS
  From September 2008 to March 2011, 42 cirrhotic patients (30 male; 12 female; mean age: 70.2 ± 7.6 years; range: 56-85 years) with HCC of Barcelona Clinic Liver Cancer stage B (n = 5) or C (n = 37; mean size: 66.6 ± 42.3 mm; mean number per patient: 3.3 ± 2.8) were treated with sorafenib at either a standard dose of 800 mg/day (n = 29; 69.1%) or at 400 mg/day with subsequent dose escalation (ramp-up strategy; n = 13, 30.9%). Baseline clinical parameters were comparable. Clinical data and side effects, laboratory analyses (in particular, serum α-fetoprotein) and radiological data (tumor response according to amended RECIST criteria) were assessed every 3 months. Survival was calculated by Kaplan-Meier analysis.
  
  
  RESULTS
  Mean follow-up was 12.2 ± 9 months (range: 1-32 months). Median overall survival was 26.1 months with overall 6- and 12-month survival rates of 92.1 and 85%, respectively. Median time to radiological progression was 8 months. The progression-free rate was 64.3%. Fatigue, skin disorders and diarrhea were the most frequent grade 3-4 side effects. Treatment discontinuation occurred in 25 patients. The starting dose for the last 13 enrolled patients was 400 mg/day; in the absence of toxicity this dosage was gradually increased to 800 mg/day after 3 weeks ('ramp-up strategy'). No grade 3/4 adverse events were observed in the ramp-up group.
  
  
  CONCLUSIONS
  Sorafenib is a valid treatment option for advanced-stage HCC. Starting at a lower dosage may allow prolonged compliance to treatment and might be considered according to patient tolerance.
authors: Gastroenterology Department, Pisa University Hospital, Via Paradisa 2, 56124 Pisa, Italy. r.sacco@ao-pisa.toscana.it
authors: Rodolfo
authors: R
authors: Sacco
authors: Irene
authors: I
authors: Bargellini
authors: Barbara
authors: B
authors: Ginanni
authors: Marco
authors: M
authors: Bertini
authors: Lorenzo
authors: L
authors: Faggioni
authors: Graziana
authors: G
authors: Federici
authors: Antonio
authors: A
authors: Romano
authors: Michele
authors: M
authors: Bertoni
authors: Salvatore
authors: S
authors: Metrangolo
authors: Emanuele
authors: E
authors: Altomare
authors: Giuseppe
authors: G
authors: Parisi
authors: Emanuele
authors: E
authors: Tumino
authors: Antonio
authors: A
authors: Scaramuzzino
authors: Giampaolo
authors: G
authors: Bresci
authors: Carlo
authors: C
authors: Bartolozzi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality; D003967:Diarrhea / Q000139:chemically induced; D018450:Disease Progression; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D011859:Radiography; D012871:Skin Diseases / Q000139:chemically induced; D000077157:Sorafenib; D016896:Treatment Outcome; D000509:alpha-Fetoproteins / Q000032:analysis
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D000509:alpha-Fetoproteins; D009536:Niacinamide; D000077157:Sorafenib