Evaluation of anti-tumour effects of oral fenretinide (4-HPR) in rats with human neuroblastoma xenografts

Abstract

Neuroblastoma, the most common extracranial solid tumour in children, may undergo spontaneous differentiation or regression, but the majority of metastatic neuroblastomas have poor prognosis despite intensive treatment. Retinoic acid and its analogues regulate growth and differentiation of neuroblastoma cells in vitro, and 13-cis retinoic acid has shown activity against human neuroblastomas in vivo. Fenretinide [N-(4-hydroxyphenyl)retinamide] has been identified as a synthetic retinoid able to induce apoptosis of numerous malignant cell lines in vitro, including neuroblastoma. Furthermore, in animal models, fenretinide has shown chemopreventive and therapeutic efficacy against several malignancies without any obvious signs of toxicity. To investigate the anti-neuroblastoma tumour growth effects of oral fenretinide in vivo we used a human neuroblastoma xenograft model. Nude rats with established neuroblastoma xenograft tumours were treated orally with fenretinide for 10 days. Five different doses of fenretinide were used ranging from 2.5 to 75 mg/rat/day (10-300 mg/kg). Tumour volumes and toxic side effects were monitored during treatment and tumour weights were recorded at autopsy. In this study we found no significant anti-tumour growth effects of fenretinide in vivo, when used as oral treatment of rats with established neuroblastoma xenograft tumours. Furthermore, there were no intra tumoural differences in treated compared to untreated tumours. However, because of the promising results of fenretinide on neuroblastoma growth in vitro, further in vivo studies are warranted using other modalities of drug administration.