A Phase I Trial of Lenalidomide in Patients with Recurrent Primary Central Nervous System Tumors

Neuro-Oncology Branch and Medical Oncology Branch, National Cancer Institute, The National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892, USA.
Clinical Cancer Research (Impact Factor: 8.72). 12/2007; 13(23):7101-6. DOI: 10.1158/1078-0432.CCR-07-1546
Source: PubMed


Inhibition of angiogenesis represents a promising new therapeutic strategy for treating primary malignant brain tumors. Lenalidomide, a potent analogue of the antiangiogenic agent thalidomide, has shown significant activity in several hematologic malignancies, and therefore we chose to explore its tolerability and activity in patients with primary central nervous system tumors.
A phase I interpatient dose escalation trial of lenalidomide in patients with recurrent primary central nervous system tumors was conducted.
Thirty-six patients were accrued to the study, of which 28 were evaluable for toxicity, the primary end point of the trial. We show that lenalidomide can be given safely up to doses of 20 mg/m(2), with the only toxicity being a probable increased risk of thromboembolic disease. Pharmacokinetic studies reveal good bioavailability, linear kinetics, and no effects of enzyme-inducing antiepileptic drugs on the metabolism of lenalidomide. No objective radiographic responses were seen in any of the treated patients. In the group of 24 patients with recurrent glioblastoma, the median time to tumor progression was <2 months and only 12.5% of patients were progression-free at 6 months.
Lenalidomide is well tolerated in patients with recurrent glioma in doses up to 20 mg/m(2). Treatment may be associated with an increased risk of thromboembolic disease. Preliminary data suggest that single agent activity may be limited in patients with recurrent glioblastoma at the doses evaluated although larger studies will be needed to confirm these observations.

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    • "Its higher potency has led to several trials in which lenalidomide is currently under investigation as an anti-cancer agent, including multiple myeloma (Moehler, 2012), Crohn’s disease (Mansfield et al., 2007), and other solid tumors (Segler and Tsimberidou, 2012). When lenalidomide was evaluated in adults with recurrent primary CNS tumors in adults, as with thalidomide, these tumors showed no objective response to treatment with lenalidomide but instead increased hematological toxicity (Fine et al., 2007). However, in PBTC-018, a phase I trial of 51 pediatric patients with recurrent, refractory, or progressive CNS tumors, objective responses were seen primarily in children with low-grade gliomas. "
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    • "Despite these results enzastaurin showed a good safety and had a better hematologic toxicity profile [123]. Many other antiangiogenics have also been tested in clinical trials [127] [128] [129] [130] [131] [132] [133] [134] [135] [136] [137] [138] [139] (Table 2). These studies showed encouraging results and are expected to improve the prognosis of HHG. "
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    • "This drug is approved by the FDA for myelodysplastic syndrome with chromosome 5q deletion and multiple myeloma. Recently, lenalidomide has been performed for recurrent brain tumors in clinical trials [78, 97]. Fine et al. reported that lenalidomide was well tolerated; however, no objective responses were seen in a phase I study [78]. "
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