Phase I trial of 13-cis-retinoic acid in children with neuroblastoma following bone marrow transplantation.

Abstract
PURPOSETreatment of neuroblastoma cell lines with 13-cis-retinoic acid (cis-RA) can cause sustained inhibition of proliferation. Since cis-RA has demonstrated clinical responses in neuroblastoma patients, it may be effective in preventing relapse after cytotoxic therapy. This phase I trial was designed to determine the maximal-tolerated dosage (MTD), toxicities, and pharmacokinetics of cis-RA administered on an intermittent schedule in children with neuroblastoma following bone marrow transplantation (BMT).PATIENTS AND METHODSFifty-one assessable patients, 2 to 12 years of age, were treated with oral cis-RA administered in two equally divided doses daily for 2 weeks, followed by a 2-week rest period, for up to 12 courses. The dose was escalated from 100 to 200 mg/m2/d until dose-limiting toxicity (DLT) was observed. A single intrapatient dose escalation was permitted.RESULTSThe MTD of cis-RA was 160 mg/m2/d. Dose-limiting toxicities in six of nine patients at 200 mg/m2/d included hypercalcemia (n = 3), ra...

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