Abstract | BACKGROUND: METHODS: We completed a phase 2 multicenter trial to evaluate the efficacy and tolerability of the mTOR inhibitor, sirolimus, for the treatment of kidney angiomyolipomas. RESULTS: 36 adults with TSC or TSC/ LAM were enrolled and started on daily sirolimus. The overall response rate was 44.4% (95% confidence intervals [CI] 28 to 61); 16/36 had a partial response. The remainder had stable disease (47.2%, 17/36), or were unevaluable (8.3%, 3/36). The mean decrease in kidney tumor size (sum of the longest diameters [sum LD]) was 29.9% (95% CI, 22 to 37; n = 28 at week 52). Drug related grade 1-2 toxicities that occurred with a frequency of >20% included: stomatitis, hypertriglyceridemia, hypercholesterolemia, bone marrow suppression ( anemia, mild neutropenia, leucopenia), proteinuria, and joint pain. There were three drug related grade 3 events: lymphopenia, headache, weight gain. Kidney angiomyolipomas regrew when sirolimus was discontinued but responses tended to persist if treatment was continued after week 52. We observed regression of brain tumors (SEGAs) in 7/11 cases (26% mean decrease in diameter), regression of liver angiomyolipomas in 4/5 cases (32.1% mean decrease in longest diameter), subjective improvement in facial angiofibromas in 57%, and stable lung function in women with TSC/ LAM (n = 15). A correlative biomarker study showed that serum VEGF-D levels are elevated at baseline, decrease with sirolimus treatment, and correlate with kidney angiomyolipoma size (Spearman correlation coefficient 0.54, p = 0.001, at baseline). CONCLUSIONS: TRIAL REGISTRATION: Clinicaltrials.gov NCT00126672.
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Authors | Sandra L Dabora, David Neal Franz, Stephen Ashwal, Arthur Sagalowsky, Francis J DiMario Jr, Daniel Miles, Drew Cutler, Darcy Krueger, Raul N Uppot, Rahmin Rabenou, Susana Camposano, Jan Paolini, Fiona Fennessy, Nancy Lee, Chelsey Woodrum, Judith Manola, Judy Garber, Elizabeth A Thiele |
Journal | PloS one
(PLoS One)
Vol. 6
Issue 9
Pg. e23379
( 2011)
ISSN: 1932-6203 [Electronic] United States |
PMID | 21915260
(Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Bacterial Agents
- Vascular Endothelial Growth Factor D
- Sirolimus
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Topics |
- Adolescent
- Adult
- Aged
- Angiomyolipoma
(chemically induced, metabolism)
- Anti-Bacterial Agents
(adverse effects, therapeutic use)
- Female
- Humans
- Kidney Neoplasms
(chemically induced, metabolism)
- Liver Neoplasms
(chemically induced, metabolism)
- Male
- Middle Aged
- Sirolimus
(adverse effects, therapeutic use)
- Tuberous Sclerosis
(drug therapy, metabolism)
- Vascular Endothelial Growth Factor D
(metabolism)
- Young Adult
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