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Redefining the Role of Doxorubicin for the Treatment of Children With Hepatoblastoma

Marcio H. Malogolowkin, Howard M. Katzenstein, Mark Krailo, Zhengjia Chen, John J. Quinn, Marleta Reynolds, Jorge A. Ortega

From the Children's Hospital Los Angeles; University of Southern California Keck School of Medicine, Los Angeles; Children's Oncology Group, Arcadia, CA; Children's Healthcare of Atlanta, Emory University, Atlanta, GA; and the Children's Memorial Medical Center, Chicago, IL

Corresponding author: Marcio H. Malogolowkin, MD, Childrens Hospital Los Angeles, Division of Hematology-Oncology, 4650 Sunset Blvd, MS #54, Los Angeles, CA 90027; e-mail: mmalogolowkin{at}chla.usc.edu

Purpose Systemic chemotherapy has improved the survival of patients with hepatoblastoma (HB). INT-0098 Intergroup Liver Tumor Study demonstrated that patients with HB treated with either cisplatin/fluorouracil/vincristine (CFV) or cisplatin/doxorubicin (CD) had a similar survival. The Children's Oncology Group adopted the less toxic CFV as the standard regimen for treating HB. However, international cooperative groups still favor the CD combination. We therefore decided to revisit the role of doxorubicin for the treatment of HB.

Methods Outcomes of patients with HB on the INT-0098 study were reviewed with an emphasis on the postevent survival time for both regimens to elucidate the role of doxorubicin in their retrieval.

Results Sixty-four of the 173 randomly assigned patients had an event. Of these, 55 experienced progression or recurrence after initial treatment. Eleven (31%) of 36 patients treated with CFV were successfully retrieved with a doxorubicin-containing regimen and surgery and remain alive at last contact, whereas only one (6%) of 18 patients treated with CD was alive after retrieval therapy.

Conclusion CFV is effective for stage I or II HB. Doxorubicin can be omitted as part of initial therapy in the majority of these patients, potentially limiting the long-term cardiac toxicities, without compromising outcome. Doxorubicin is effective in rescuing patients with recurrent disease after CFV and should be incorporated as a means of intensifying initial therapy for advanced-stage, nonmetastatic HB. Outcome of patients with metastatic disease at diagnosis is poor, and improving their survival will require new therapeutic approaches.

Supported by Grant No. CA 98543 from the Children's Oncology Group.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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