Paclitaxel: An effective antineoplastic agent in the treatment of xenotransplanted hepatoblastoma

Background. Hepatoblastoma is an uncommon liver tumor of infancy and early childhood. Though most patients with nonmetastatic hepatoblastomas can be c ured by defining surgical strategies and chemotherapy regimes, new drugs ar e needed for children with advanced hepatoblastomas. The activity of paclit axel as a new antineoplastic agent with limited experience in pediatric onc ology was studied in a xenograft model. Procedure. Hepatoblastoma cell susp ensions from three children were transplanted subcutaneously into nude mice NMRI (nu/nu). One of the primary tumors was an embryonal multifocal hepato blastoma, whereas the other tumors were embryonal/fetal hepatoblastomas loc alized on a liver lobe. After 4 weeks, xenografted tumor sizes reached 50-1 00 mm(3). The xenografted tumors resembled their originals histologically a nd produced high levels of alpha-fetoprotein. The efficiency of paclitaxel at equitoxic doses was analyzed. Results. Paclitaxel produced an effect in all three hepatoblastomas. There was a significant reduction of tumor volum e (P < 0.001) and alpha-fetoprotein levels after chemotherapy (P < 0.0001). The proliferation activity of the tumor cells corresponded with these resu lts. Histologically, after treatment with paclitaxel the tumor regression w as 35%-49%. The mechanism of paclitaxel action could be demonstrated by lig ht microscopy immunohistochemistry and electron microscopy. Conclusions. Th e preliminary results in phase I trials of solid tumors in children and the results of this study suggest that paclitaxel in phase II studies can now be entertained for patients with hepatoblastoma. (C) 1999 Wiley-Liss, Inc.