Comparative activity of cisplatin, ifosfamide, doxorubicin, carboplatin, and etoposide in heterotransplanted hepatoblastoma

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 study the tumor's response to drugs is needed urgently.

Methods: Hepatoblastoma cell suspensions from three children were transplanted subcutaneously into NMRI nude mice (nu/nu). One of the primary tumors was a embryonal multifocal hepatoblastoma, whereas the Other tumors were embryonal/fetal hepatoblastomas localized to one liver lobe. The xenograft tumors resembled their original tumors histologically and produced high levels of alpha-fetoprotein. The mice who received the tumors were given ifosfamide, cisplatin, doxorubicin, carboplatin, and etoposide as single agents. Thereafter, the tumor growth rate and alpha-fetoprotein levels in the animal sera were measured before and after chemotherapy and compared with the control group. After chemotherapy, the tumors were studied by conventional histology.

Results: The tumors in the nude mice derived from the multifocal hepatoblastoma reacted minimally 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 doxorubicin, respectively. The tumors displayed a moderate reduction in size after treatment with ifosfamide, etoposide, and carboplatin. The responses to the different cytostatic agents also corresponded with serum alpha-fetoprotein levels and mitotic rates in the tumor cells.

Conclusions: To the authors' knowledge, this is the first time an in vivo model 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 of multidrug resistance mechanisms in hepatoblastoma.