Differentiating agents in pediatric malignancies: retinoids in neuroblastoma

Curr Oncol Rep. 2000 Nov;2(6):511-8. doi: 10.1007/s11912-000-0104-y.


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 morphologic differentiation of human neuroblastoma cell lines. Phase I trials have shown 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 improves event-free survival in high-risk neuroblastoma. Because 4-HPR achieves multi-log cell kills in neuroblastoma cell lines that are resistant to ATRA and 13-cis-RA, a pediatric phase I trial is in progress to determine the maximum tolerated dose of 4-HPR, with a view toward giving 4-HPR after completion of myeloablative therapy and 13-cis-RA.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology*
  • Child
  • Drug Administration Schedule
  • Fenretinide / administration & dosage
  • Fenretinide / adverse effects
  • Fenretinide / pharmacology*
  • Humans
  • Isotretinoin / administration & dosage
  • Isotretinoin / adverse effects
  • Isotretinoin / pharmacology*
  • Neuroblastoma / drug therapy*
  • Randomized Controlled Trials as Topic
  • Receptors, Retinoic Acid / drug effects
  • Receptors, Retinoic Acid / physiology
  • Tretinoin / administration & dosage
  • Tretinoin / adverse effects
  • Tretinoin / pharmacology*
  • Tumor Cells, Cultured


  • Antineoplastic Agents
  • Receptors, Retinoic Acid
  • Fenretinide
  • Tretinoin
  • Isotretinoin