Retinoid therapy of high-risk neuroblastoma.

Abstract

Retinoids are derivatives of vitamin A that include all trans-retinoic acid (ATRA), 13-cis-retinoic acid, (13-cis-RA), and fenretinide (4-HPR). High levels of either ATRA or 13-cis-RA can cause arrest of cell growth and morphological differentiation of human neuroblastoma cell lines, and phase I trials showed that higher and more sustained drug levels were obtained with 13-cis-RA relative to ATRA. A phase III randomized trial showed that high-dose, pulse therapy with 13-cis-RA given after completion of intensive chemoradiotherapy (with or without autologous bone marrow transplantation) significantly improved event-free survival in high-risk neuroblastoma. The cytotoxic retinoid 4-HPR achieved multi-log cell kills in neuroblastoma cell lines resistant to ATRA and 13-cis-RA, and a pediatric phase I trial has shown it to be well tolerated. Cytotoxicity of 4-HPR is mediated at least in part by increasing tumor cell ceramide levels and combining 4-HPR with ceramide modulators increased anti-tumor activity in pre-clinical models. Thus, further clinical trials of 4-HPR in neuroblastoma, and of 4-HPR in combination with ceramide modulators, are warranted.

• Authors: C Patrick Reynolds, Katherine K Matthay, Judith G Villablanca, Barry J Maurer
• Journal: Cancer letters (Cancer Lett) Vol. 197 Issue 1-2 Pg. 185-92 (Jul 18 2003) ISSN: 0304-3835 [Print] Ireland
• PMID: 12880980 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S., Review)

Chemical References

• Antineoplastic Agents
• Receptors, Retinoic Acid
• Tretinoin

Topics

• Antineoplastic Agents (therapeutic use)
• Clinical Trials as Topic
• Humans
• Neuroblastoma (drug therapy)
• Receptors, Retinoic Acid (drug effects, metabolism)
• Tretinoin (therapeutic use)