Redefining the role of doxorubicin for the treatment of children with hepatoblastoma

• Type of Material: Article
• Authors: MH Malogolowkin, Children's Memorial Hospital; Howard Katzenstein, Emory University; M Krailo, Children's Memorial Hospital; Zhengjia Chen, Emory University; JJ Quinn, Children's Memorial Hospital; M Reynolds, Children's Memorial Hospital; JA Ortega, Children's Memorial Hospital
• Language: English
• Date: 2008-09-15
• Publisher: American Society of Clinical Oncology
• Publication Version: Final Published Version
• Copyright Statement: © 2008 by American Society of Clinical Oncology
• Final Published Version (URL): http://dx.doi.org/10.1200/JCO.2006.09.7204
• Title of Journal or Parent Work: Journal of Clinical Oncology
• ISSN: 0732-183X
• Volume: 26
• Issue: 14
• Start Page: 2379
• End Page: 2383
• Grant/Funding Information: Supported by Grant No. CA 98543 from the Children's Oncology Group.
• Keywords: Humans; Child; Infusions, Intravenous; Hepatoblastoma; Vincristine; Drug Administration Schedule; Fluorouracil; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Liver Neoplasms; Doxorubicin; Disease-Free Survival; Treatment Outcome; Cisplatin
• Research Categories: Health Sciences, Oncology; Health Sciences, Pharmacology

Abstract

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. © 2008 by American Society of Clinical Oncology.