Differentiating agents in pediatric malignancies: retinoids in 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 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.
See also:
- All-Trans-Retinoic Acid (ATRA - analogues and/or derivatives);
- The Di Bella Method (A Fixed Part - All-Trans Retinoic Acid, Analogues and/or Derivatives);
- Solution of retinoids in vitamin E in the Di Bella Method biological multitherapy;
- The Di Bella Method (A Fixed Part - Alpha tocopheryl acetate/Vitamin E);
- Neuroblastoma: Complete objective response to biological treatment.