title: Cisplatin, doxorubicin, and delayed surgery for childhood hepatoblastoma: a successful approach--results of the first prospective study of the International Society of Pediatric Oncology.
abstract: OBJECTIVE
  Hepatoblastoma (HB) is a rare malignant liver tumor which occurs almost exclusively in childhood. In the 1970s, survival was approximately 20% to 30%. Since the introduction of cisplatin (PLA) and doxorubicin (DO) into the chemotherapy regimens used to treat these patients, the survival rate has improved dramatically. In most recent studies, primary surgery preceded chemotherapy. In this study by the liver group of the International Society of Pediatric Oncology the aim was to improve survival and reduce operative morbidity and mortality by using preoperative chemotherapy.
  
  
  METHODS
  After biopsy and assessment of pretreatment extent of disease all patients were treated with continuous 24-hour intravenous infusion of PLA 80 mg/m(2) followed by DO 60 mg/m(2) over 48 hours (PLADO). After four courses of this chemotherapy, patients were reassessed. Where possible, the primary tumor was resected and treatment completed with two more courses of chemotherapy.
  
  
  RESULTS
  One hundred fifty-four patients were registered in the study, and 138 received preoperative chemotherapy. One hundred thirteen (82%) showed a partial response with tumor shrinkage and serial decrease of serum alpha-fetoprotein levels. One hundred fifteen patients had delayed surgery, and 106 (including six with liver transplants) had complete resection of primary tumor. Five-year event-free survival was 66%, and overall survival was 75%.
  
  
  CONCLUSIONS
  This study demonstrates that international collaboration on a large scale is feasible. The toxicity of chemotherapy and morbidity of surgery were acceptable and the overall survival gratifyingly high. We now regard PLADO chemotherapy and delayed surgery to be the best available treatment for children with HB. Other treatment programs should be measured against this standard.
authors.affiliation: Institute of Child Health, St Bartholomew's Hospital, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Pritchard
authors.forename: J
authors.initials: J
authors.lastname: Brown
authors.forename: E
authors.initials: E
authors.lastname: Shafford
authors.forename: G
authors.initials: G
authors.lastname: Perilongo
authors.forename: P
authors.initials: P
authors.lastname: Brock
authors.forename: C
authors.initials: C
authors.lastname: Dicks-Mireaux
authors.forename: J
authors.initials: J
authors.lastname: Keeling
authors.forename: A
authors.initials: A
authors.lastname: Phillips
authors.forename: A
authors.initials: A
authors.lastname: Vos
authors.forename: J
authors.initials: J
authors.lastname: Plaschkes
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D018197:Hepatoblastoma / Q000097:blood / Q000188:drug therapy* / Q000601:surgery*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008113:Liver Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000601:surgery*; D008297:Male; D011300:Preoperative Care; D011446:Prospective Studies; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D000509:alpha-Fetoproteins; D004317:Doxorubicin; D002945:Cisplatin