Hypercalcemia Induced by 13‐cis‐Retinoic Acid in a Patient with Neuroblastoma

Abstract

Hypercalcemia is a potential dosage-related adverse effect of 13-cis-retinoic acid in patients with neuroblastoma. Severe hypercalcemia requiring dosage reduction has been reported in children receiving 13-cis-retinoic acid 200 mg/m2/day and in those with concurrent renal impairment receiving 160 mg/m2/day. A 12-year-old girl without renal dysfunction, diagnosed with neuroblastoma, developed severe hypercalcemia requiring several hospitalizations while receiving 13-cis-retinoic acid 160 mg/m2/day. Her hypercalcemia resolved with hydration, diuretic therapy, and temporary discontinuation of 13-cis-retinoic acid. Despite a 50% dosage reduction to 80 mg/m2/day, severe hypercalcemia recurred with the next treatment cycle. Further treatment with 13-cis-retinoic acid was made tolerable by shortening the duration of the remaining cycles. Serum calcium levels should be monitored in patients with neuroblastoma who receive 13-cis-retinoic acid.

A comparison of the effectiveness of soy protein isolate and fish oil for reducing the severity of retinoid-induced hypertriglyceridemia

“…Among group differences were also noted for TC, HDL-C, 8 13-cis retinoic was dissolved in 10 g of ethanol and stirred into dietary oils; after the retinoid had dissolved, ethanol was removed by bubbling nitrogen through the mixture, and dl-␣-tocopherol and Tenox 20 were incorporated into the mixture. 9 Food grade antioxidant (Eastman Products, Kingsport, TN). Contained (g/kg): tertiary butyl hydroquinone, 200; anhydrous citric acid, 100; propylene glycol, 700.…”

Hypercalcemia induced by 13 cis‐retinoic acid in patients with neuroblastoma

“…Patient 2, who experienced hypercalcemia (serum calcium 17.0 mg/dL), was asymptomatic and had been receiving 13‐cis‐RA at 130 mg/m 2 per day. Belden and Ragucci demonstrated that hypercalcemia may be a dosage‐limiting adverse effect of 13‐cis‐RA in children receiving an initial dosage of 160 mg/m 2 per day 9 . This dose is not likely to develop either clinical toxicity or episodes of hypercalcemia, but patient 2 developed hypercalcemia.…”

Predicting, Monitoring, and Managing Hypercalcemia Secondary to 13-Cis-Retinoic Acid Therapy in Children With High-risk Neuroblastoma

“…Persistent grade 4 hypercalcemia occurred despite 50% dose reduction of MTD that resolved when fluconazole was discontinued. 5 Another patient treated with fluconazole for fungal pneumonia during his second cycle of retinoid therapy developed hypercalcemia having been normocalcaemic during his first cycle. 6 In vitro studies have demonstrated that metabolism of 13-cis-RA is principally reliant on cytochrome P450 enzymes, CYP3A4 and CYP2C8.…”

“…Other authors preferred maintaining MTD but shortening the duration of each course to 7 days, every 14 to 21 days, to maintain the effective pattern of high-dose, pulsed retinoid therapy. 5,7,22 We propose an algorithm for the management of a patient on 13-cis-RA (Fig. 2).…”

“…[1][2][3] Common side effects are mainly well tolerated mild toxicities including dry skin, anorexia, myalgia, and headache. 4 Significant hypercalcemia is increasingly reported with the use of higher doses, [5][6][7][8] with hypercalcemia identified as a novel dose-limiting toxicity in phase I trials of 13-cis-RA in children with high-risk neuroblastoma. [9][10][11] Toxicities were graded according to the National Cancer Institute Common Toxicity Criteria.…”