We report 19 episodes of hypercalcemia in three children treated with 13-cis-retinoic acid (13-cis-RA) as a post-consolidation therapy for high-risk neuroblastoma. There was no concomitant overload in 13-cis-RA blood levels. Blood calcium fell after arrest of 13-cis-RA intake. Half dosage retinoid treatment resumption did not prevent the recurrence of hypercalcemia. Concomitant biological values showed massive bone resorption. Hence, hypercalcemia seemed not secondary to 13-cis-RA overload but rather to inter-individual variability in its interaction with bone metabolism. Current guidelines in case of hypercalcemia are to reduce 13-cis-RA dosage. Instead we propose to maintain the therapeutic dosage, but to shorten the duration of courses.
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Marabelle et al. (2008) studied this question.