Minimal Adjuvant Chemotherapy for Pediatric Hepatoblastoma Resected at Diagnosis


Key Points

  • Patients eligible for upfront resection had good disease control and low toxicity with minimal adjuvant chemotherapy.
  • Event-free survival was 92% at 4 years and 88% at 5 years.

In an analysis from the Children’s Oncology Group phase III AHEP0731 trial reported in The Lancet Oncology, Katzenstein et al found that minimal adjuvant chemotherapy with two cycles of cisplatin, fluorouracil, and vincristine was associated with disease control in pediatric patients with hepatoblastoma resected at diagnosis. As noted by the investigators, among the minority of newly diagnosed patients with resectable disease at diagnosis, typical adjuvant treatment consists of 4 to 6 cycles of such chemotherapy.

Study Details

The trial enrolled patients in four risk groups to receive risk-adapted therapy. The current report involves 49 patients from the low-risk stratum of the trial. Eligible patients were aged ≤ 21 years and had histologically confirmed stage I or II hepatoblastoma without 100% pure fetal stage I or small-cell undifferentiated histology, elevated serum α-fetoprotein (> 100 ng/mL), complete resection at diagnosis, and had received no previous chemotherapy or other hepatoblastoma-directed therapy.

Patients received two 21-day cycles of chemotherapy within 42 days of resection, consisting of cisplatin at 100 mg/m2 per dose or 3.3 mg/kg per dose for children < 10 kg over 6 hours on day 1, fluorouracil at 600 mg/m2 per dose or 20 mg/kg per dose for children < 10 kg on day 2, and vincristine at 1.5 mg/m2 per day to a maximum dose of 2 mg or 0.05 mg/kg per day for children < 10 kg on days 2, 9, and 16. The primary outcome was investigator-assessed event-free survival. As specified by the protocol, the primary endpoint was analyzed 6 years after enrollment (with a cutoff date in December 2017).

Event-Free Survival and Adverse Events

Median follow-up time for the 49 evaluable patients was 42 months. Event-free survival was 92% at 4 years and 88% at 5 years. Surgical complications (bile leaks) occurred in 2 patients (4%).

The most common grade 3 or 4 adverse events were febrile neutropenia (14%), infections (8%), diarrhea (8%), and decreased neutrophil count (6%). Ototoxicity occurred in one patient (2%). No treatment-related deaths were observed.

The investigators concluded, “Minimal postoperative chemotherapy with two cycles of cisplatin, fluorouracil, and vincristine can ensure disease control in patients with hepatoblastoma resected at diagnosis. Our results show that dose reduction of ototoxic agents is a safe, effective treatment for these children.”

Howard M. Katzenstein, MD, of Nemours Children’s Specialty Care and Wolfson Children’s Hospital, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by the National Institutes of Health. For full disclosures of the study authors, visit

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