Sorafenib and cisplatin/doxorubicin (PLADO) in pediatric hepatocellular carcinoma

Pediatr Blood Cancer. 2012 Apr;58(4):539-44. doi: 10.1002/pbc.23295. Epub 2011 Sep 15.

Abstract

Purpose: 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.

Patients and 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.

Conclusion: 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.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Benzenesulfonates / administration & dosage*
  • Benzenesulfonates / adverse effects
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / therapy*
  • Child
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Female
  • Follow-Up Studies
  • Humans
  • Liver Neoplasms / mortality
  • Liver Neoplasms / therapy*
  • Liver Transplantation*
  • Male
  • Niacinamide / analogs & derivatives
  • Phenylurea Compounds
  • Prospective Studies
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / adverse effects
  • Pyridines / administration & dosage*
  • Pyridines / adverse effects
  • Retrospective Studies
  • Sorafenib
  • Survival Rate
  • Transplantation, Homologous

Substances

  • Benzenesulfonates
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Pyridines
  • Niacinamide
  • Doxorubicin
  • Sorafenib
  • Cisplatin

Supplementary concepts

  • AP protocol 1