Poster Presentation Advances in Neuroblastoma Research Congress 2016

Premature physeal closure following prolonged fenretinide administration in patients with neuroblastoma (#311)

Angela Steineck 1 , John Mackenzie 2 , Clare J. Twist 3
  1. Department of Pediatrics, Stanford University, Palo Alto, CA, United States
  2. Department of Radiology, University of California at San Francisco, San Francisco, CA, USA
  3. Divison of Pediatric Hematology/Oncology, Stanford University, Palo Alto, CA, USA

Background: Despite advances in multimodal therapy for high risk (HR) neuroblastoma, survival remains suboptimal. Retinoid therapy with 13-cis-retinoic acid (13cisRA) has contributed to improved outcomes. The synthetic retinoid fenretinide has demonstrated in vitro toxicity against neuroblastoma cells that have developed resistance to other retinoids, and has a favorable toxicity profile in Phase I trials. Skeletal effects, including premature physeal closure, have been described with other retinoids, but have not been described in children treated with fenretinide to date.

 

Methods: Retrospective chart review identified two patients with HR neuroblastoma who developed premature physeal closure following protracted oral fenretinide therapy.

 

Results: Patient 1 (Caucasian girl), and Patient 2 (African American boy) were diagnosed at ages 6 and 5 years respectively with HR stage 4, single copy MYCN neuroblastoma. Both failed induction therapy and received investigational 131I-MIBG followed by consolidation chemotherapy and stem cell rescue, local radiation therapy, and 13cisRA. Due to persistent metastatic disease, both received oral fenretinide (capsular formulation, 800 mg PO TID) for a total of 70 and 61 cycles, respectively, and ultimately achieved complete remission. During the prolonged administration of oral fenretinide over at least 5 years, both patients developed asymmetric premature physeal closure of multiple long bones, resulting in limb length discrepancies and angular deformities. Nearly a decade off therapy, both are alive and in remission from neuroblastoma.

 

Conclusion: Phase I and II studies of fenretinide in children have not reported skeletal toxicity as a late effect of therapy. The unusual and strikingly similar radiographic and clinical findings strongly suggest that the skeletal abnormalities may be a consequence of protracted fenretinide exposure. Further study of potential skeletal toxicity in neuroblastoma patients receiving retinoid therapy is indicated to better understand the mechanism and risk factors of retinoid bone toxicity.