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Stage III Childhood Liver Cancer
Postsurgically staged, stage III and presurgically staged, PRETEXT stage 4 hepatoblastoma
Stage III hepatocellular carcinoma

Postsurgically staged, stage III and presurgically staged, PRETEXT stage 4 hepatoblastoma

Standard treatment options

In approximately 75% of children and adolescents with initially unresectable hepatoblastoma, tumors can be rendered resectable with cisplatin-based preoperative chemotherapy, and 60% to 65% will survive disease free. A randomized clinical trial has demonstrated similar efficacy with cisplatin/vincristine/fluorouracil, or cisplatin/doxorubicin in the treatment of hepatoblastoma; the combination of cisplatin/vincristine/fluorouracil, however, resulted in considerably less toxicity.[1] However, another chemotherapy regimen including doxorubicin/cisplatin at different doses and schedules demonstrated comparable results with less toxicity.[2] A combination of ifosfamide, cisplatin, and doxorubicin has also been successfully used in the treatment of advanced-stage disease.[3] Patients whose tumors remain unresectable should be considered for alternative chemotherapy, such as high-dose cisplatin with etoposide,[4] radiation therapy,[5,6] direct hepatic infusion of chemotherapeutic agents,[7] or orthotopic liver transplantation.[2,8-11]

Stage III hepatocellular carcinoma
In a randomized trial, cisplatin plus either vincristine/fluorouracil or doxorubicin given by continuous infusion was ineffective in adequately treating unresectable hepatocellular carcinoma. Therapy failed in 23 of 25 patients with stage III disease.[12] No particular treatment for unresectable hepatocellular carcinoma has proved especially 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. Several therapeutic options have produced successful outcomes in some adults with hepatocellular carcinoma, including cryosurgery, intratumoral injection of alcohol, radiotherapeutic approaches, and liver transplantation.[9-11] (Refer to the PDQ summary on Adult Primary Liver Cancer Treatment for more information.)


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]

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]

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]

Douglass EC, Pediatric Oncology Group: Phase II Study of CBDCA and CBDCA/5-FU/VCR in Pediatric Patients with Unresectable or Metastatic (Stage III/IV) Hepatoblastoma, with CDDP/VP-16 for Those Who Remain Unresectable Following Initial Chemotherapy (Summary Last Modified 09/93), POG-9345, Clinical trial, Closed. [PDQ Clinical Trial]

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]

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]

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]

Koneru B, Flye MW, Busuttil RW, et al.: Liver transplantation for hepatoblastoma. The American experience. Ann Surg 213 (2): 118-21, 1991.  [PUBMED Abstract]

Bilik R, Superina R: Transplantation for unresectable liver tumors in children. Transplant Proc 29 (7): 2834-5, 1997.  [PUBMED Abstract]

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]

Reyes JD, Carr B, Dvorchik I, et al.: Liver transplantation and chemotherapy for hepatoblastoma and hepatocellular cancer in childhood and adolescence. J Pediatr 136 (6): 795-804, 2000. [PUBMED Abstract]

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]


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