J. Fuchs et al., COMPARATIVE ACTIVITY OF CISPLATIN, IFOSFAMIDE, DOXORUBICIN, CARBOPLATIN, AND ETOPOSIDE IN HETEROTRANSPLANTED HEPATOBLASTOMA, Cancer, 83(11), 1998, pp. 2400-2407
BACKGROUND. Hepatoblastoma is the most common primary malignant liver
tumor affecting infants and young children. Recent clinical experience
with advanced hepatoblastoma shows that a reliable in vivo model to s
tudy the tumor's response to drugs is needed urgently. METHODS. Hepato
blastoma cell suspensions from three children were transplanted subcut
aneously into NMRI nude mice (nu/nu), One of the primary tumors was a
embryonal multifocal hepatoblastoma, whereas the other tumors were emb
ryonal/ fetal hepatoblastomas localized to one liver lobe. The xenogra
ft tumors resembled their original tumors histologically and produced
high levels of alpha-fetoprotein. The mice who received the tumors wer
e given ifosfamide, cisplatin, doxorubicin, carboplatin, and etoposide
as single agents. Thereafter, the tumor growth rate and alpha-fetopro
tein levels in the animal sera were measured before and after chemothe
rapy and compared viith the control group. After chemotherapy, the tum
ors were studied by conventional histology. RESULTS, The tumors in the
nude mice derived from the multifocal hepatoblastoma reacted minimall
y against four of the five cytotoxic agents, whereas cisplatin reduced
the tumor volume significantly. There was a marked reduction in tumor
volume in the other tumors after application of cisplatin and doxorub
icin, respectively. The tumors displayed a moderate reduction in size
after treatment with ifosfamide, etoposide, and carboplatin. The respo
nses to the different cytostatic agents also corresponded with serum a
lpha-fetoprotein levels and mitotic rates in the tumor cells. CONCLUSI
ONS. To the authors' knowledge, this is the first time an in vivo mode
l for analyzing the effects of chemotherapy on hepatoblastoma has been
established. The animal model may be suited for the evaluation of new
drugs for the treatment of hepatoblastoma and for the investigation o
f multidrug resistance mechanisms in hepatoblastoma. (C) 1998 American
Cancer Society.