Abstract | BACKGROUND: METHODS:
Regorafenib was administered to 32 subjects with gastrointestinal stromal tumor on a 3-week-on, 1-week-off basis. Plasma levels of NO and ET-1 were measured at baseline, 2, 4, and 6 weeks of therapy. Data analysis was by Wilcoxon rank-sum and paired t-tests. RESULTS: Twenty subjects (63%) developed regorafenib-induced hypertension. Two weeks after starting regorafenib therapy, plasma ET-1 levels increased (25% increase, P < 0.05) and NO was suppressed (20% decrease, P < 0.05). These normalized after 1-week washout but ET-1 rose again by 30% (P < 0.05) and NO fell by 50% (P < 0.05) after restarting regorafenib. CONCLUSIONS: These findings indicate that regorafenib induces a coordinated and reversible suppression of NO and stimulation of ET-1. Whether NO and ET-1 might predict therapeutic efficacy in these patients requires further study.
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Authors | Nilka de Jesus-Gonzalez, Emily Robinson, Radostin Penchev, Margaret von Mehren, Michael C Heinrich, William Tap, Qian Wang, George Demetri, Suzanne George, Benjamin D Humphreys |
Journal | American journal of hypertension
(Am J Hypertens)
Vol. 25
Issue 10
Pg. 1118-23
(Oct 2012)
ISSN: 1941-7225 [Electronic] United States |
PMID | 22785409
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Angiogenesis Inhibitors
- Biomarkers
- Endothelin-1
- Phenylurea Compounds
- Pyridines
- regorafenib
- Nitric Oxide
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Topics |
- Angiogenesis Inhibitors
(adverse effects)
- Biomarkers
(blood)
- Endothelin-1
(blood, drug effects)
- Female
- Gastrointestinal Stromal Tumors
(physiopathology)
- Humans
- Hypertension
(chemically induced)
- Male
- Middle Aged
- Nitric Oxide
(blood)
- Phenylurea Compounds
(adverse effects, therapeutic use)
- Pyridines
(adverse effects, therapeutic use)
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