TY - JOUR
T1 - Phase I trial of lenalidomide in pediatric patients with recurrent, refractory, or progressive primary CNS tumors
T2 - Pediatric Brain Tumor Consortium Study PBTC-018
AU - Warren, Katherine E.
AU - Goldman, Stewart
AU - Pollack, Ian F.
AU - Fangusaro, Jason
AU - Schaiquevich, Paula
AU - Stewart, Clinton F.
AU - Wallace, Dana
AU - Blaney, Susan M.
AU - Packer, Roger
AU - MacDonald, Tobey
AU - Jakacki, Regina
AU - Boyett, James M.
AU - Kun, Larry E.
PY - 2011/1/20
Y1 - 2011/1/20
N2 - Purpose: A phase I trial of lenalidomide was performed in children with recurrent, refractory, or progressive primary CNS tumors to estimate the maximum-tolerated dose (MTD) and to describe the toxicity profile and pharmacokinetics. Patients and Methods: Lenalidomide was administered by mouth daily for 21 days, repeated every 28 days. The starting dose was 15 mg/m 2/d orally, and the dose was escalated according to a modified continuous reassessment method. Correlative studies included pharmacokinetics obtained from consenting patients on course 1, day 1, and at steady-state (between days 7 and 21). Results: Fifty-one patients (median age, 10 years; range, 2 to 21 years) were enrolled. Forty-four patients were evaluable for dose finding, and 49 patients were evaluable for toxicity. The primary toxicity was myelosuppression, but the MTD was not defined because doses up to 116 mg/m 2/d were well-tolerated during the dose-finding period. Two objective responses were observed (one in thalamic juvenile pilocytic astrocytoma and one in optic pathway glioma) at dose levels of 88 and 116 mg/m2/d. Twenty-three patients, representing all dose levels, received ≥ six cycles of therapy. Pharmacokinetic analysis demonstrated that the lenalidomide area under the concentration-time curve from 0 to 24 hours and maximum plasma concentration increased with dosage over the range studied. Conclusion: Lenalidomide was tolerable in children with CNS tumors at doses of 116 mg/m 2/d during the initial dose-finding period. The primary toxicity is myelosuppression. Antitumor activity, defined by both objective responses and long-term stable disease, was observed, primarily in patients with low-grade gliomas.
AB - Purpose: A phase I trial of lenalidomide was performed in children with recurrent, refractory, or progressive primary CNS tumors to estimate the maximum-tolerated dose (MTD) and to describe the toxicity profile and pharmacokinetics. Patients and Methods: Lenalidomide was administered by mouth daily for 21 days, repeated every 28 days. The starting dose was 15 mg/m 2/d orally, and the dose was escalated according to a modified continuous reassessment method. Correlative studies included pharmacokinetics obtained from consenting patients on course 1, day 1, and at steady-state (between days 7 and 21). Results: Fifty-one patients (median age, 10 years; range, 2 to 21 years) were enrolled. Forty-four patients were evaluable for dose finding, and 49 patients were evaluable for toxicity. The primary toxicity was myelosuppression, but the MTD was not defined because doses up to 116 mg/m 2/d were well-tolerated during the dose-finding period. Two objective responses were observed (one in thalamic juvenile pilocytic astrocytoma and one in optic pathway glioma) at dose levels of 88 and 116 mg/m2/d. Twenty-three patients, representing all dose levels, received ≥ six cycles of therapy. Pharmacokinetic analysis demonstrated that the lenalidomide area under the concentration-time curve from 0 to 24 hours and maximum plasma concentration increased with dosage over the range studied. Conclusion: Lenalidomide was tolerable in children with CNS tumors at doses of 116 mg/m 2/d during the initial dose-finding period. The primary toxicity is myelosuppression. Antitumor activity, defined by both objective responses and long-term stable disease, was observed, primarily in patients with low-grade gliomas.
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U2 - 10.1200/JCO.2010.31.3601
DO - 10.1200/JCO.2010.31.3601
M3 - Article
C2 - 21149652
AN - SCOPUS:79951986245
SN - 0732-183X
VL - 29
SP - 324
EP - 329
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 3
ER -