title: Sorafenib and cisplatin/doxorubicin (PLADO) in pediatric hepatocellular carcinoma.
abstract: OBJECTIVE
  Overall survival is poor in children with primary unresectable hepatocellular carcinoma. Sorafenib has been shown to significantly improve progression-free survival in adult hepatocellular carcinoma (HCC) patients. We evaluated the experience of PLADO (cisplatin 80 mg/m(2) /day, doxorubicin 2 × 30 mg/m(2) /day) in combination with sorafenib in pediatric HCC patients.
  
  
  METHODS
  Clinical data of 12 patients (7-16 years), 7 with unresectable tumor, were retrospectively assessed.
  
  
  RESULTS
  In total 6/12 (50%) patients are in complete remission after a median follow-up of 20 months (4 with PLADO/sorafenib/resection, 2 with liver transplantation after local relapse). Of the seven patients with unresectable tumor, PLADO/sorafenib resulted in partial response (PR) in four, stable disease (SD) in two, and progression in one. Three are alive in CR after complete resection after 12 (alternative therapy after two cycles PLADO/sorafenib), 12 and 18 months (six cycles PLADO/sorafenib), respectively. All four patients with elevated alpha-fetoprotein levels had a marked drop after two cycles. Of the five patients with primary complete tumor resection one is alive disease-free at 27 months. Four had local or metastatic relapses (13, 7, 12, and 13 months), two of whom were rescued by liver transplantation (CR after 25 and 32 months). The main toxicity attributable to sorafenib was a hand-foot skin reaction (HFSR) in seven patients.
  
  
  CONCLUSIONS
  Sorafenib in combination with PLADO may be a promising approach in pediatric HCC; HFSR was the most important toxicity. Data based on prospective studies are needed to evaluate pharmacokinetics, resectability rates, and survival in pediatric HCC treated with sorafenib.
authors.affiliation: Department of Pediatric Hematology and Oncology, Children's Hospital of the Ludwig-Maximilians-University, Munich, Germany. irene.schmid@med.uni-muenchen.de
authors.forename: Irene
authors.initials: I
authors.lastname: Schmid
authors.forename: Beate
authors.initials: B
authors.lastname: Häberle
authors.forename: Michael H
authors.initials: MH
authors.lastname: Albert
authors.forename: Selim
authors.initials: S
authors.lastname: Corbacioglu
authors.forename: Birgit
authors.initials: B
authors.lastname: Fröhlich
authors.forename: Norbert
authors.initials: N
authors.lastname: Graf
authors.forename: Birgit
authors.initials: B
authors.lastname: Kammer
authors.forename: Udo
authors.initials: U
authors.lastname: Kontny
authors.forename: Ivo
authors.initials: I
authors.lastname: Leuschner
authors.forename: Hans-Gerhard
authors.initials: HG
authors.lastname: Scheel-Walter
authors.forename: Wolfram
authors.initials: W
authors.lastname: Scheurlen
authors.forename: Sebastian
authors.initials: S
authors.lastname: Werner
authors.forename: Thomas
authors.initials: T
authors.lastname: Wiesel
authors.forename: Dietrich
authors.initials: D
authors.lastname: von Schweinitz
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001557:Benzenesulfonates / Q000008:administration & dosage* / Q000009:adverse effects; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000628:therapy*; D002648:Child; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008113:Liver Neoplasms / Q000401:mortality / Q000628:therapy*; D016031:Liver Transplantation; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects; D012189:Retrospective Studies; D000077157:Sorafenib; D015996:Survival Rate; D014184:Transplantation, Homologous
chemical_list: D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D009536:Niacinamide; D004317:Doxorubicin; D000077157:Sorafenib; D002945:Cisplatin