Liver Tumour Studies - Hepatoblastoma and Hepatocellular Carcinoma
- Compare the efficacy of cisplatin with or without doxorubicin in terms of tumor
response, complete resection rate, overall survival, and event free survival in
children with standard risk hepatoblastoma.
- Compare the toxicity of cisplatin with or without doxorubicin in this patient
- Evaluate whether an intensive multiagent regimen including carboplatin, cisplatin, and
doxorubicin improves the response rate to chemotherapy and subsequent resection rate of
children with high risk hepatoblastoma or hepatocellular carcinoma.
OUTLINE: This is a randomized, multicenter study. All hepatoblastoma patients are intended
to be treated with primary chemotherapy. Hepatoblastoma patients are stratified by risk
(standard vs high).
Patients receive cisplatin IV over 24 hours on day 1, beginning within 15 days of diagnosis.
Standard risk patients are then randomized to one of two treatment arms. High risk
hepatoblastoma patients and hepatocellular carcinoma patients receive a separate multiagent
- Arm I: Patients receive cisplatin IV over 24 hours and doxorubicin IV over 48 hours
beginning on day 15. Treatment repeats every 21 days for a maximum of 5 courses. Tumor
response is evaluated prior to the second course. Patients with responsive disease
receive the remaining 2 courses of the preoperative phase, then undergo delayed primary
surgery if their tumors are deemed resectable, prior to receiving 2 additional courses
of chemotherapy. Patients whose tumors are still unresectable after 3 courses receive 2
more courses of chemotherapy, then undergo surgery if feasible. Patients with stable
disease are considered for radical surgery or salvage chemotherapy. Patients with
unresectable tumors after 5 courses may be considered for liver transplant or salvage
- Arm II: Patients receive cisplatin IV over 24 hours every 15 days for a maximum of 5
additional courses. Tumor response is evaluated after the second course. Patients with
responsive disease receive another 2 courses of cisplatin. Patients with resectable
tumors after 4 courses undergo delayed primary surgery, then receive 2 more courses of
cisplatin. Patients whose tumors are still unresectable after 4 courses receive 2 more
courses of cisplatin, then undergo surgery if their tumors are resectable. Patients
with stable disease may be moved to the high risk regimen or considered for radical
surgery. Patients with unresectable tumors after 6 courses may be considered for liver
transplant or salvage chemotherapy.
Patients with high risk hepatoblastoma or unresectable hepatocellular carcinoma receive
cisplatin IV over 24 hours on days 29, 57, and 85, and carboplatin IV over 1 hour followed
by doxorubicin IV over 48 hours on days 15, 43, and 71. Patients with responsive resectable
disease undergo surgery either after day 43 or within 3 weeks of day 85 of preoperative
chemotherapy, then receive another 2 courses of carboplatin and doxorubicin on days 1 and 29
post surgery, and one more course of cisplatin on day 15 post surgery, for a total of 5
courses each. Patients with responsive but unresectable disease after day 85 also receive 2
more courses of carboplatin and doxorubicin alternating with 1 course of cisplatin.
Definitive surgery will be re-considered after these further courses of chemotherapy.
Patients with stable disease at day 43 or a tumor that remains unresectable after completion
of chemotherapy may be considered for liver transplant.
Patients with a resectable hepatocellular carcinoma have primary surgery followed by
alternating courses of cisplatin, and carboplatin and doxorubicin for a total of 4 courses
of cisplatin and 3 courses of carboplatin and doxorubicin.
Patients are followed every 2-3 months for 2 years, every 6 months for 1 year, then annually
PROJECTED ACCRUAL: A total of 170-260 patients (85-130 patients per treatment arm) will be
accrued for this study over 5.5 years.
Allocation: Randomized, Primary Purpose: Treatment
Giorgio Perilongo, MD
Azienda Ospedaliera di Padova
United States: Federal Government