title: Effects of the combined treatment with thalidomide, megestrol and interleukine-2 in cirrhotic patients with advanced hepatocellular carcinoma. A pilot study.
abstract: BACKGROUND
  Thalidomide, an anti-angiogenic agent, does not have a good therapeutic effect for advanced hepatocellular carcinoma when used alone. Megestrol and interleukin-2 have been proposed as a palliative treatment for hepatocellular carcinoma. AIMS.: We assessed the effectiveness/safety of a combined therapy with thalidomide+megestrol+interleukin-2 in cirrhotic patients with advanced hepatocellular carcinoma.
  
  
  METHODS
  Nine cirrhotic patients with advanced hepatocellular carcinoma received oral megestrol (160 mg/day) and thalidomide (from 50 mg/day to the maximal tolerated dose). Four patients also received subcutaneous interleukin-2 (1 million U/day for 21 days/month).
  
  
  RESULTS
  The maximal tolerated dose of thalidomide was 150 mg/day. All patients complained of sedation and other neurological or digestive adverse effects. In all but one patient the adverse effects disappeared after thalidomide withdrawal or dose reduction. Interleukin-2 administration caused a flu-like syndrome and a reaction at the injection site. During treatment, alpha-fetoprotein increased in six patients, remained stable in two and decreased in one. Eight patients showed tumour progression and one had a stable disease. Eight patients died. The median survival was 9.9 (range 2.6-18.6) months.
  
  
  CONCLUSIONS
  In cirrhotic patients, the combined treatment with thalidomide+megestrol (+/-interleukin-2) does not control hepatocellular carcinoma growth, possibly due to the low tolerance to thalidomide and interleukin-2 preventing the use of appropriate dosages.
authors.affiliation: Department of Internal Medicine Cardioangiology Hepatology, University of Bologna, Via Albertoni 15, 40138 Bologna, Italy.
authors.forename: F Mirici
authors.initials: FM
authors.lastname: Cappa
authors.forename: M C
authors.initials: MC
authors.lastname: Cantarini
authors.forename: G
authors.initials: G
authors.lastname: Magini
authors.forename: A
authors.initials: A
authors.lastname: Zambruni
authors.forename: C
authors.initials: C
authors.lastname: Bendini
authors.forename: V
authors.initials: V
authors.lastname: Santi
authors.forename: M
authors.initials: M
authors.lastname: Bernardi
authors.forename: F
authors.initials: F
authors.lastname: Trevisani
mesh_terms: D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D003967:Diarrhea / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects; D008103:Liver Cirrhosis / Q000150:complications* / Q000188:drug therapy; D008113:Liver Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008535:Megestrol / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009367:Neoplasm Staging; D010865:Pilot Projects; D016019:Survival Analysis; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D014202:Tremor / Q000139:chemically induced; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D018931:Antineoplastic Agents, Hormonal; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D000509:alpha-Fetoproteins; D013792:Thalidomide; D008535:Megestrol