Stage IV hepatoblastoma
        Standard treatment options
Stage IV hepatocellular carcinoma
Current Clinical Trials

Stage IV hepatoblastoma

The outcome for hepatoblastoma that is metastaticat diagnosis is not good, but cure is possible in 25% to 30% of patients.[1-4] In a study employing a well-tolerated regimen of doxorubicin/cisplatin chemotherapy, over 50% of patients with metastases at presentation survived 5 years from diagnosis. Half of these survivors developed progressive disease that was successfully treated with surgery and other interventions.[1-5] For patients with PRETEXT stage 4 disease with or without pulmonary metastases who respond to chemotherapy and achieve complete remission of extrahepatic disease, liver transplantation can produce disease-free survival in a high percentage of patients.[6] If possible, stage IV patients with resected primary tumor should have any remaining pulmonary metastases surgically removed. A randomized clinical trial compared cisplatin/vincristine/fluorouracil and cisplatin/doxorubicin in the treatment of hepatoblastoma. Although outcome was nominally higher for children receiving cisplatin/doxorubicin, this difference was not statistically significant, and the combination of cisplatin/vincristine/flourouracil was less toxic than the regimen of cisplatin/doxorubicin to which it was compared.[3] Replacement of some cisplatin by carboplatin in the cisplatin/vincristine/doxorubicin regimen was associated with a decrease in event-free survival.[7] A combination of ifosfamide, cisplatin, and doxorubicin has also been successfully used in the treatment of advanced-stage disease.[8] Patients whose tumors remain unresectable should be considered for alternative chemotherapy, such as irinotecan,[9,10] high-dose cisplatin with etoposide, radiation therapy,[2,11] or direct hepatic infusion of chemotherapeutic agents.[12,13]If metastatic disease is controlled, orthotopic liver transplantation [4,6,14-17] has been successful.

The standard regimen is four courses of cisplatin/vincristine/fluorouracil [3] or doxorubicin/cisplatin combination chemotherapy followed by attempted complete tumor resection. If the tumor is completely removed, two postoperative courses of the same chemotherapy should be given. If the tumor is not resectable after four courses of chemotherapy, alternative therapies should be considered.

• Chemotherapy with high-dose cisplatin/etoposide or continuous infusion of doxorubicin.



• Radiation therapy followed by re-exploration, if metastatic disease is controlled.



• Chemoembolization by hepatic arterial infusion.



• Orthotopic liver transplantation, if metastatic disease is controlled.



• Phase I or phase II clinical trials of chemotherapy.

In two prospective trials, cisplatin plus either vincristine/fluorouracil or continuous infusion doxorubicin was ineffective in adequately treating 25 patients with metastatic hepatocellular carcinoma.[18,19] No particular treatment for unresectable hepatocellular carcinoma has proved effective in the pediatric age group. Occasional patients may benefit from treatment with cisplatin/doxorubicin therapy, especially if localized hepatic tumor shrinks adequately to allow resection of disease. (Refer to the PDQ summary on Adult Primary Liver Cancer Treatment for more information.)

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage IV childhood liver cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References

1. Ortega JA, Krailo MD, Haas JE, et al.: Effective treatment of unresectable or metastatic hepatoblastoma with cisplatin and continuous infusion doxorubicin chemotherapy: a report from the Childrens Cancer Study Group. J Clin Oncol 9 (12): 2167-76, 1991.  [PUBMED Abstract]
   
   
2. Douglass EC, Reynolds M, Finegold M, et al.: Cisplatin, vincristine, and fluorouracil therapy for hepatoblastoma: a Pediatric Oncology Group study. J Clin Oncol 11 (1): 96-9, 1993.  [PUBMED Abstract]
   
   
3. Ortega JA, Douglass EC, Feusner JH, et al.: Randomized comparison of cisplatin/vincristine/fluorouracil and cisplatin/continuous infusion doxorubicin for treatment of pediatric hepatoblastoma: A report from the Children's Cancer Group and the Pediatric Oncology Group. J Clin Oncol 18 (14): 2665-75, 2000.  [PUBMED Abstract]
   
   
4. Perilongo G, Brown J, Shafford E, et al.: Hepatoblastoma presenting with lung metastases: treatment results of the first cooperative, prospective study of the International Society of Paediatric Oncology on childhood liver tumors. Cancer 89 (8): 1845-53, 2000.  [PUBMED Abstract]
   
   
5. Pritchard J, Brown J, Shafford E, et al.: Cisplatin, doxorubicin, and delayed surgery for childhood hepatoblastoma: a successful approach--results of the first prospective study of the International Society of Pediatric Oncology. J Clin Oncol 18 (22): 3819-28, 2000.  [PUBMED Abstract]
   
   
6. Otte JB, Pritchard J, Aronson DC, et al.: Liver transplantation for hepatoblastoma: results from the International Society of Pediatric Oncology (SIOP) study SIOPEL-1 and review of the world experience. Pediatr Blood Cancer 42 (1): 74-83, 2004.  [PUBMED Abstract]
   
   
7. Malogolowkin MH, Katzenstein H, Krailo MD, et al.: Intensified platinum therapy is an ineffective strategy for improving outcome in pediatric patients with advanced hepatoblastoma. J Clin Oncol 24 (18): 2879-84, 2006.  [PUBMED Abstract]
   
   
8. von Schweinitz D, Hecker H, Harms D, et al.: Complete resection before development of drug resistance is essential for survival from advanced hepatoblastoma--a report from the German Cooperative Pediatric Liver Tumor Study HB-89. J Pediatr Surg 30 (6): 845-52, 1995.  [PUBMED Abstract]
   
   
9. Katzenstein HM, Rigsby C, Shaw PH, et al.: Novel therapeutic approaches in the treatment of children with hepatoblastoma. J Pediatr Hematol Oncol 24 (9): 751-5, 2002.  [PUBMED Abstract]
   
   
10. Palmer RD, Williams DM: Dramatic response of multiply relapsed hepatoblastoma to irinotecan (CPT-11). Med Pediatr Oncol 41 (1): 78-80, 2003.  [PUBMED Abstract]
    
    
11. Habrand JL, Nehme D, Kalifa C, et al.: Is there a place for radiation therapy in the management of hepatoblastomas and hepatocellular carcinomas in children? Int J Radiat Oncol Biol Phys 23 (3): 525-31, 1992.  [PUBMED Abstract]
    
    
12. Sue K, Ikeda K, Nakagawara A, et al.: Intrahepatic arterial injections of cisplatin-phosphatidylcholine-Lipiodol suspension in two unresectable hepatoblastoma cases. Med Pediatr Oncol 17 (6): 496-500, 1989.  [PUBMED Abstract]
    
    
13. Malogolowkin MH, Stanley P, Steele DA, et al.: Feasibility and toxicity of chemoembolization for children with liver tumors. J Clin Oncol 18 (6): 1279-84, 2000.  [PUBMED Abstract]
    
    
14. Koneru B, Flye MW, Busuttil RW, et al.: Liver transplantation for hepatoblastoma. The American experience. Ann Surg 213 (2): 118-21, 1991.  [PUBMED Abstract]
    
    
15. Bilik R, Superina R: Transplantation for unresectable liver tumors in children. Transplant Proc 29 (7): 2834-5, 1997.  [PUBMED Abstract]
    
    
16. Laine J, Jalanko H, Saarinen-Pihkala UM, et al.: Successful liver transplantation after induction chemotherapy in children with inoperable, multifocal primary hepatic malignancy. Transplantation 67 (10): 1369-72, 1999.  [PUBMED Abstract]
    
    
17. Austin MT, Leys CM, Feurer ID, et al.: Liver transplantation for childhood hepatic malignancy: a review of the United Network for Organ Sharing (UNOS) database. J Pediatr Surg 41 (1): 182-6, 2006.  [PUBMED Abstract]
    
    
18. Katzenstein HM, Krailo MD, Malogolowkin MH, et al.: Hepatocellular carcinoma in children and adolescents: results from the Pediatric Oncology Group and the Children's Cancer Group intergroup study. J Clin Oncol 20 (12): 2789-97, 2002.  [PUBMED Abstract]
    
    
19. Czauderna P, Mackinlay G, Perilongo G, et al.: Hepatocellular carcinoma in children: results of the first prospective study of the International Society of Pediatric Oncology group. J Clin Oncol 20 (12): 2798-804, 2002.  [PUBMED Abstract]
    
    

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