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

Purpose: 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.
(© 2021 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)