Abstract | OBJECTIVE: METHODS: This was an open-label extension phase of a prospective, phase 1-2 trial (NCT00411619) in patients ≥3 years of age with SEGA associated with TSC. Patients received oral everolimus starting at 3 mg/m2 per day and subsequently titrated, subject to tolerability, to attain whole blood trough concentrations of 5-15 ng/mL. Change in SEGA volume, seizures, and safety assessments were the main outcome measures. RESULTS: Of 28 patients enrolled, 25 were still under treatment at the time of analysis. Median dose was 5.3 mg/m2/day and median treatment duration was 34.2 months (range 4.7-47.1). At all time points (18, 24, 30, and 36 months), primary SEGA volume was reduced by ≥30% from baseline (treatment response) in 65%-79% of patients. All patients reported ≥1 adverse event (AE), mostly grade 1/2 in severity, consistent with that previously reported, and none led to everolimus discontinuation. The most commonly reported drug-related AEs were upper respiratory infections (85.7%), stomatitis (85.7%), sinusitis (46.4%), and otitis media (35.7%). No drug-related grade 4 or 5 events occurred. CONCLUSION:
Everolimus therapy is safe and effective for longer term (median exposure 34.2 months) treatment of patients with TSC with SEGA. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that everolimus, titrated to trough serum levels of 5-15 ng/mL, was effective in reducing tumor size in patients with SEGA secondary to TSC for a median of 34 months.
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Authors | Darcy A Krueger, Marguerite M Care, Karen Agricola, Cindy Tudor, Maxwell Mays, David Neal Franz |
Journal | Neurology
(Neurology)
Vol. 80
Issue 6
Pg. 574-80
(Feb 05 2013)
ISSN: 1526-632X [Electronic] United States |
PMID | 23325902
(Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Everolimus
- Sirolimus
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Topics |
- Adolescent
- Adult
- Antineoplastic Agents
(therapeutic use)
- Astrocytoma
(drug therapy)
- Child
- Child, Preschool
- Everolimus
- Female
- Humans
- Male
- Sirolimus
(analogs & derivatives, therapeutic use)
- Young Adult
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