Risk-adapted treatment for childhood hepatoblastoma: final report of the second study of the International Society of Paediatric Oncology—SIOPEL 2 § G. Perilongo a, *, E. Shafford b , R. Maibach c , D. Aronson d , L. Brugie`res e , P. Brock f , M. Childs g , P. Czauderna h , G. MacKinlay i , J.B. Otte j , J. Pritchard k,1 , R. Rondelli l , M. Scopinaro m , C. Staalman n , J. Plaschkes o a Division of Paediatric Haematology-Oncology, University Hospital, via Giustiniani 3-35128, Padova, Italy b Royal London Hospital, London, UK c Swiss Institute for Applied Cancer Research, Berne, Switzerland d Paediatric Surgical Centre, Academic Medical Centre, Amsterdam, The Netherlands e Service d’Oncologie Pediatrique, Institute ‘‘Gustave Roussy’’, Villejiuf, France f Hospital for Sick Children, Great Ormond Street, London, UK g UKCCSG Data Centre, University of Leicester, Leicester, UK h Department of Pediatric Surgery, Medical University, Gdansk, Poland i Service de Chirurgia Pediatrique, Abdominal et General University Catholique de Louvain, Cliniques Universitaires Saint Luc, Bruxells, Belgium j Royal Hospital for Sick Children, Edinburgh, UK k Department of Paediatric Surgery, Institute of Child Health, London, UK l Division of Paediatric Haematology-Oncology, Hospital ‘‘Sant’Orsola’’, Bologna, Italy m Department of Haematology, Oncology, Hospital de Pediatria Garrahn, Buenos Aires, Argentina n Department of Pediatric Radiology Division, Academic Medical Center, Amsterdam, The Netherlands o Pediatric Surgical Department, University Children Hospital, Berne, Switzerland Received 8 May 2003; received in revised form 2 June 2003; accepted 13 June 2003 Abstract SIOPEL 2 was a pilot study designed to test the efficacy and toxicity of two chemotherapy (CT) regimens, one for patients with hepatoblastoma (HB) confined to the liver and involving no more than three hepatic sectors (‘standard-risk (SR) HB’), and one for those with HB extending into all four sectors and/or with lung metastases or intra-abdominal extra hepatic spread ‘high-risk (HR) HB’. SR-HBpatientsweretreatedwithfourcoursesofcisplatin(CDDP),atadoseof80mg/m 2 every 14 days, delayed surgery, and then two more similar CDDP courses. HR-HB patients were given CDDP alternating every 14 days with carboplatin (CARBO), 500 mg/m 2 , and doxorubicin (DOXO), 60 mg/m 2 . Two courses of CARBO/DOXO and one of CDDP were given postoperatively. Between Octo- ber 1995 and May 1998, 77 SR-HB (10 of whom were actually treated with the HR protocol) and 58 HR-HB patients were registered and all 135 could be evaluated. Response rates for the entire SR-HB and HR-HB groups were 90% (95% CI 80–96%) and 78% (95% CI 65–87%), and resection rates were 97% (95% CI 87–99%) and 67% (95% CI 54–79%) including several children undergoing liver transplantation. For SR-HB patients, 3-year overall and progression-free survivals were 91% ( Æ 7%) and 89% ( Æ 7%) and for the HR-HB group 53% ( Æ 13%) and 48% ( Æ 13%), respectively. The short-term toxicity of these regimens was acceptable, with no toxic deaths. A treatment strategy based on CDDP monotherapy and surgery thus appears effective in SR-HB but, despite CT intensifica- tion, only half of the HR-HB patients are long-term survivors. For SR-HB patients, the efficacy of CDDP monotherapy and the CDDP/DOXO (‘PLADO’) combination are now being compared in a prospective randomised trial (SIOPEL 3). # 2003 Elsevier Ltd. All rights reserved. Keywords: Hepatoblastoma; Cisplatin; Children; Chemotherapy; Prognostic factor 0959-8049/$ - see front matter # 2003 Elsevier Ltd. All rights reserved. doi:10.1016/j.ejca.2003.06.003 European Journal of Cancer 40 (2004) 411–421 www.ejconline.com § For the Childhood Liver Tumor Strategy Group (SIOPEL) of the International Society of Paediatric Oncology (SIOP), University of Leicester, Hearts of Oak House, 9 Princess Road West, Leicester LE1 6TH, UK. Participating members are shown in the Appendix. * Corresponding author. Tel.: +39-049-821-3505/06; fax: +39-049-821-3510. E-mail address: giorgio.perilongo@unipd.it (G. Perilongo). 1 Present address: Department of Haematology/Oncology, Royal Hospital for Sick Children, Edinburgh, UK.