Treatment of unresectable and metastatic hepatoblastoma: a pediatric oncology group phase II study.
OBJECTIVE
To estimate the disease-response rate, proportion of patients whose tumors can be made resectable, event-free survival (EFS), and toxicity in children with unresectable or metastatic hepatoblastoma (HB) after sequential treatment with the following: (1) carboplatin (CARBO); (2) CARBO, vincristine, and fluorouracil (CARBO-VCR-5-FU); and (3) high-dose cisplatin and etoposide (HDDP-ETOP).


METHODS
Thirty-three assessable patients with stage III (n = 22) and stage IV (n = 11) HB were treated sequentially with one course of CARBO (700 mg/m(2)), followed by three courses of CARBO (700 mg/m(2)), day 0; 5-FU (1,000 mg/m(2)/d), by continuous infusion days 0 to 2; and VCR (1.5 mg/m(2)), days 0, 7, and 14. After that therapy, patients whose tumors were resectable underwent surgery and then received two additional courses of CARBO-VCR-5-FU. Children whose tumors remained unresectable after CARBO-VCR-5-FU or who demonstrated no response or progressive disease during this therapy received two courses of HDDP (40 mg/m(2)/d), days 1 to 5; and ETOP (100 mg/m(2)/d), days 2 to 4.


RESULTS
Five-year EFS estimates were 59% +/- 11% for stage III disease (n = 22) and 27% +/- 16% for stage IV disease (n = 11), respectively (P =.037). Twenty-seven (82%) of 33 patients had at least a partial response to chemotherapy; 18 (55%) of 33 responded to CARBO; 24 (80%) of 30 responded to CARBO and CARBO-VCR-5-FU; and nine (75%) of 12 responded to HDDP-ETOP. Surgical resection was achieved in 19 (58%) of 33 patients, including 15 (68%) of 22 stage III patients and four (36%) of 11 stage IV patients. Five-year EFS for patients whose tumors were completely resected was 79% +/- 10%.


CONCLUSIONS
Patients treated sequentially with CARBO, CARBO-VCR-5-FU, and HDDP-ETOP had response rates and EFS comparable to other therapeutic regimens. This regimen is effective in treating localized, unresectable HB and potentially has less toxicity than other regimens. Novel approaches are needed for patients with metastatic disease.
Katzenstein
Howard M
HM
Department of Pediatrics and Surgery, Northwestern University and Children's Memorial Hospital, Chicago, IL, USA. howard.katzenstein@choa.org
London
Wendy B
WB
Douglass
Edwin C
EC
Reynolds
Marleta
M
Plaschkes
Jack
J
Finegold
Milton J
MJ
Bowman
Laura C
LC
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D018197:Hepatoblastoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D009362:Neoplasm Metastasis; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage
D014750:Vincristine; D005047:Etoposide; D016190:Carboplatin; D002945:Cisplatin; D005472:Fluorouracil