Current chemotherapeutic approaches for hepatoblastoma.
Cisplatin-based chemotherapy has markedly improved the survival of patients with standard-risk hepatoblastoma (HB). However, treatment results for patients with metastatic disease remain unsatisfactory. As a result, the current therapeutic strategy for HB is to decrease dose intensity for standard-risk tumors in order to reduce chemotherapy-related toxicity and to intensify chemotherapy in combination with new drugs to develop new therapies and improve the outcome of patients with metastatic disease. Results from various trials of The North American Cooperative Study demonstrated that patients with localized disease achieved long-term survival following treatment with a combination of cisplatin, 5-fluorouracil, and vincristine (C5V). In the ongoing Children's Oncology Group (COG) trial, AHEP0731, patients with stage I pure fetal histology are classified as very low risk and treated with resection only, and patients with any stage IV disease or any stage plus an alpha-fetoprotein level at diagnosis of <100 ng/ml are classified as high risk and receive up-front window therapy followed by C5V + doxorubicin in an attempt to discover novel efficacious agents. The early International Childhood Liver Tumors Strategy Group (SIOPEL) trial, SIOPEL-1, demonstrated that a combination of cisplatin + doxorubicin (PLADO) is effective. In the SIOPEL-3SR trial, cisplatin alone was proved to be non-inferior to PLADO for standard-risk HB. In the SIOPEL-4 trial, intensified preoperative cisplatin was administered on a weekly basis, and this approach achieved the highest survival rate ever reported for patients, even those with metastatic disease. SIOPEL, COG, and the Japanese Study Group for Pediatric Liver Tumor (JPLT) have established the Children's Hepatoma International Collaboration (CHIC) to create a common risk classification and initiate international clinical trials in order to further improve the outcome of children with HB.
Department of Pediatrics, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan, wataken@kuhp.kyoto-u.ac.jp.
Kenichiro
K
Watanabe
D002648:Child; D002945:Cisplatin / Q000008:administration & dosage*; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D005472:Fluorouracil / Q000008:administration & dosage*; D018197:Hepatoblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010372:Pediatrics / Q000379:methods; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage*
D014750:Vincristine; D002945:Cisplatin; D005472:Fluorouracil