Cisplatin plus pirarubicin chemotherapy and combination ifomide, etoposide, pirarubicin, and carboplatin chemotherapy for hepatoblastoma.

Abstract

9534 Background: The Japanese Study Group for Pediatric Liver Tumor is running cooperative treatment studies on hepatoblastoma (HB) since 1991. The main aim in JPLT-1 study was to evaluate the efficacy of cisplatin/pirarubicin. A total of 145 cases were registered and their 6-year overall survival (OS) and event-free survival (EFS) were 73.4% and 66%, respectively (J Pediatr Surg 37: 851-6, 2002). Since the outcomes of advanced HB cases remained poor, JPLT-2 protocol was launched in 1999 to evaluate the cure rate of risk-stratified HB: standard risk HB (a tumor involving three or fewer sectors of the liver) and high risk HB (a tumor involving all sectors of the liver or with metastasis). Methods: In JPLT-2, children with HB who were younger than 15 years of age were eligible for inclusion in the study. The cisplatin/pirarubicin regimen (CITA) is kept as the first line and the second line regimen consisting of ifomide, etoposide, pirarubicin, and carboplatin (ITEC) is recommended for the tumors resistant to CITA. For high risk HB cases, high dose chemotherapy with stem cell transplantation (SCT) was carried out. Results: Until 2007, 245 hepatoblastoma cases have been registered in JPLT-2, and 203 cases have completed the protocol including 69 cases (18%) with metastatic tumors. The 3-year OS and EFS of the cases with standard risk HB were 96% and 76%, while that of the cases with high risk HB was 54% and 34%. Among 34 high risk HB cases (30 with metastatic HB and 4 with unresectable HB) who underwent high dose regimen with SCT, only 21 cases (57%) were cured, indicating that high dose chemotherapy with SCT is not so effective in advanced tumors. With this regimen, 5 cases suffered treatment-related death. And the late phase complications were 3 cases with maldevelopment, 13 with cardiac complications, 20 with ototoxicity and 4 with second malignancies. Conclusions: As compared with other regimens, CITA regimens achieved similar or superior rates of survival among children with standard-risk HB. ITEC regimens and high dose chemotherapy with SCT is not so effective in high- risk HB. More promising strategies including liver transplantation and new targeting drugs should be developed for high risk HB. No significant financial relationships to disclose.