Cisplatin alone safe and effective for patients with standard-risk hepatoblastoma

Cisplatin monotherapy was noninferior to cisplatin plus doxorubicin and achieved similar complete resection and survival rates in children with standard-risk hepatoblastoma.

The International Childhood Liver Tumour Strategy Group conducted a prospective trial (SIOPEL 3) to determine whether doxorubicin could be safely omitted from the treatment of standard-risk (a tumor involving less than three sectors of the liver) hepatoblastoma. Researchers randomly assigned children aged younger than 16 years to cisplatin alone (n=126) or cisplatin plus doxorubicin (n=129).

There was a 90% response rate in the cisplatin group and a 95% response rate in the cisplatin plus doxorubicin group. In intention-to-treat analysis, the rate of complete resection was 95% in the cisplatin group and 93% in the cisplatin plus doxorubicin group demonstrating the noninferiority of cisplatin with a difference of 1.4% (95% CI, –4.1 to 7.0).

In per-protocol analysis, the complete resection rate was 99% with cisplatin and 95% with cisplatin plus doxorubicin (difference=3.9%; 95% CI, –0.3 to 8.1). Median follow-up time was 46 months. The three-year OS rates were similar among patients assigned to cisplatin (95%) and those assigned to cisplatin plus doxorubicin (93%). Event-free survival rates were 83% for cisplatin and 85% for cisplatin plus doxorubicin.

There was no difference in risk for relapse or death, and ototoxicity or nephrotoxicity between the treatment groups. Frequency of acute grade-3 or grade-4 adverse events was higher among patients in the cisplatin plus doxorubicin group (74.4%) than in those in the cisplatin alone group (20.6%). – by Christen Haigh

Perilongo G. N Engl J Med. 2009;361:1662-1670.

In pediatric oncology, the need to identify lower-risk patient populations that can be treated successfully with less intensive therapy and fewer long-term side effects is an ongoing challenge. The favorable outcome with cisplatin monotherapy in the SIOPEL 3 standard risk hepatoblastoma group is an important finding.

For those of us in North America who treat our patients according to the Children's Oncology Group studies, the difficulty arises in translating the standard-risk patient population into a similar group based on our prechemotherapy surgical staging system. Many of the patients in the SIOPEL 3 standard-risk group would be surgical stage I or II patients who traditionally would receive four courses of cisplatin-based chemotherapy without doxorubicin and with excellent long-term event-free survival rates of 90% to 100%.

As both SIOPEL and COG learn more about the risk stratification of hepatoblastoma patients, the optimal time for surgical intervention and improved strategies for high-risk patients, the better we will all be in optimizing and personalizing the care for each patient.

– Kimberly Davies, MD

Assistant Clinical Professor of Pediatrics, Harvard Medical School, Boston