Differentiating agents in pediatric malignancies: retinoids in neuroblastoma.
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.
Reynolds
C P
CP
Division of Hematology-Oncology, Children's Hospital of Los Angeles and The University of Southern California School of Medicine, 4650 Sunset Boulevard. Los Angeles, CA 90054-0700, USA. preynolds@chla.usc.edu
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D002648:Child; D004334:Drug Administration Schedule; D017313:Fenretinide / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D015474:Isotretinoin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D009447:Neuroblastoma / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D018168:Receptors, Retinoic Acid / Q000187:drug effects / Q000502:physiology; D014212:Tretinoin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D018168:Receptors, Retinoic Acid; D017313:Fenretinide; D014212:Tretinoin; D015474:Isotretinoin