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Hypercalcemia is a frequent side effect of 13-cis-retinoic acid treatment in patients with high-risk neuroblastoma.

AbstractPURPOSE:
13-cis-Retinoic acid (13-cisRA) is used as a postconsolidation treatment in patients with high-risk neuroblastoma. Hypercalcemia is a known side effect of retinoids. Frequency, symptoms, treatment, and risk factors for hypercalcemia were analyzed.
PATIENTS:
Data were retrospectively analyzed for 350 patients registered in the German Neuroblastoma trials NB97 and NB04 who were treated with high-risk protocols-including myeloablative chemotherapy with autologous stem cell transplantation (SCT) or maintenance therapy-and had received 13-cisRA between January 1, 2000 and December 31, 2010.
RESULTS:
Hypercalcemia was reported in 78 patients (22.3%), and 37 patients (10.6%) developed Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or 4 hypercalcemia. The calcium levels were 2.5-4.6 mmol/L (median 3.1 mmol/L). Patients with a single kidney were at a higher risk of developing hypercalcemia (p = .001). Regarding postinduction treatment, 69 of 280 patients with SCT (24.6%) and nine of 70 patients without SCT (12.9%) developed hypercalcemia during 13-cisRA treatment (p = .037). Most patients developed hypercalcemia in the first cycle of 13-cisRA, and only in a single cycle. Hypercalcemia symptoms were frequent but moderate. In most patients, treatment with 13-cisRA was continued without dose reduction in subsequent cycles.
CONCLUSION:
In this cohort, grades 3 and 4 hypercalcemia were observed more often than previously reported. A single kidney and pretreatment with myeloablative chemotherapy with stem cell transplantation were identified as potential risk factors for the development of hypercalcemia.
AuthorsMarc Hoemberg, Ruth Schwenzfeur, Frank Berthold, Thorsten Simon, Barbara Hero
JournalPediatric blood & cancer (Pediatr Blood Cancer) Vol. 69 Issue 2 Pg. e29374 (02 2022) ISSN: 1545-5017 [Electronic] United States
PMID34569150 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2021 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.
Chemical References
  • Isotretinoin
Topics
  • Drug-Related Side Effects and Adverse Reactions (drug therapy)
  • Female
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Hypercalcemia (chemically induced)
  • Isotretinoin (adverse effects)
  • Male
  • Neuroblastoma (drug therapy)
  • Retrospective Studies
  • Solitary Kidney (drug therapy)
  • Transplantation, Autologous

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