What is the recommended chemotherapy regimen for hepatoblastoma?

Recommended Chemotherapy Regimen for Hepatoblastoma

Cisplatin monotherapy is the recommended standard chemotherapy regimen for children with standard-risk hepatoblastoma, while cisplatin plus doxorubicin (PLADO) is recommended for high-risk disease. 1, 2

Risk Stratification and Treatment Approach

Risk stratification is essential for determining the appropriate chemotherapy regimen:

Standard-Risk Hepatoblastoma

• Standard-risk defined as tumor involving three or fewer liver sectors with alpha-fetoprotein (AFP) >100 ng/mL 1
• Cisplatin monotherapy (80 mg/m² per 24 hours every 14 days) is recommended as it achieves similar complete resection rates and survival outcomes as combination therapy while causing fewer adverse events 1
• Treatment typically consists of 3 preoperative and 2 postoperative cycles 1

High-Risk Hepatoblastoma

• High-risk defined as metastatic disease, tumor in all liver segments, abdominal extrahepatic disease, major vascular invasion, low AFP, or tumor rupture 2
• Dose-dense cisplatin-based chemotherapy is recommended with the SIOPEL-4 regimen: 2
  • Preoperative cycles A1-A3: cisplatin 80 mg/m² on day 1 and 70 mg/m² on days 8,15,29,36,43,57, and 64; plus doxorubicin 30 mg/m² on days 8,9,36,37,57, and 58
  • Additional cycle B for unresectable tumors: doxorubicin plus carboplatin
  • Postoperative cycle C: doxorubicin plus carboplatin

Special Considerations

Very Low-Risk Disease

• Patients with stage I pure fetal histology may be classified as very low risk and treated with resection only without adjuvant chemotherapy 3

Resectable Disease at Diagnosis

• For completely resected tumors at diagnosis, minimal postoperative chemotherapy with just two cycles of cisplatin, fluorouracil, and vincristine (C5V) can ensure disease control 4
• C5V regimen: cisplatin (100 mg/m²) on day 1, fluorouracil (600 mg/m²) on day 2, and vincristine (1.5 mg/m² to maximum 2 mg) on days 2,9, and 16 of a 21-day cycle 4

Ototoxicity Prevention

• Sodium thiosulfate should be administered to prevent cisplatin-induced ototoxicity in children with non-metastatic hepatoblastoma 5
• Recommended dose: 16 g/m² or 20 g/m² administered 6 hours after each cisplatin dose 5
• This approach has been shown not to compromise survival outcomes in non-metastatic disease 5

Treatment Sequence and Surgical Considerations

• Preoperative chemotherapy followed by delayed surgery is the standard approach for most patients 6
• This strategy improves resectability and reduces operative morbidity and mortality 6
• Complete surgical resection of all tumor lesions is critical for cure 5
• Liver transplantation should be considered for patients with PRETEXT IV disease (involving all four liver sections) or complex PRETEXT III disease that remains unresectable after chemotherapy 5

Monitoring and Response Assessment

• Response assessment should be based on dynamic CT or MRI studies 5
• Modified RECIST criteria should be used to evaluate treatment response 5
• Serial measurement of serum AFP levels is essential to monitor response 6
• Complete remission is defined as complete resection of all tumor lesions and normalization of AFP levels 2

Potential Adverse Effects

• Common grade 3-4 adverse events include: 2
  • Hematological toxicity (anemia, neutropenia, thrombocytopenia) in up to 97% of patients
  • Febrile neutropenia in approximately 71% of patients
  • Documented infections in 27% of patients
  • Anorexia in 35% of patients
  • Mucositis in 11% of patients
• Moderate-to-severe ototoxicity occurs in approximately 50% of patients receiving cisplatin-based regimens without otoprotection 2

By following these evidence-based recommendations, optimal outcomes can be achieved for children with hepatoblastoma while minimizing unnecessary treatment-related toxicity.