Background: Preoperative cisplatin alone may be as effective as cisplatin plus doxorubicin in standard-risk hepatoblastoma
(a tumor involving three or fewer sectors of the liver that is associated with an alpha-fetoprotein level of >100 ng per
Methods: Children with standard-risk hepatoblastoma who were younger than 16 years of age were eligible for
inclusion in the study. After they received one cycle of cisplatin (80 mg per square meter of body-surface area per 24 hours),
we randomly assigned patients to receive cisplatin (every 14 days) or cisplatin plus doxorubicin administered in three preoperative
cycles and two postoperative cycles. The primary outcome was the rate of complete resection, and the trial was powered to
test the noninferiority of cisplatin alone (<10% difference in the rate of complete resection).
Results: Between June
1998 and December 2006, 126 patients were randomly assigned to receive cisplatin and 129 were randomly assigned to receive
cisplatin plus doxorubicin. The rate of complete resection was 95% in the cisplatin-alone group and 93% in the cisplatin-doxorubicin
group in the intention-to-treat analysis (difference, 1.4%; 95% confidence interval [CI],-4.1 to 7.0); these rates were 99%
and 95%, respectively, in the per-protocol analysis. Three-year event-free survival and overall survival were, respectively,
83% (95% CI, 77 to 90) and 95% (95% CI, 91 to 99) in the cisplatin group, and 85% (95% CI, 79 to 92) and 93% (95% CI, 88 to
98) in the cisplatin-doxorubicin group (median follow-up, 46 months). Acute grade 3 or 4 adverse events were more frequent
with combination therapy (74.4% vs. 20.6%).
Conclusions: As compared with cisplatin plus doxorubicin, cisplatin monotherapy
achieved similar rates of complete resection and survival among children with standard-risk hepatoblastoma. Doxorubicin can
be safely omitted from the treatment of standard-risk hepatoblastoma.