Thalidomide Effective for Refractory Bleeding from Gastrointestinal Vascular Malformations

In a small, randomized, controlled trial, thalidomide significantly reduced bleeding episodes, blood transfusions, and hospitalizations.

Every experienced gastroenterologist has encountered patients who have refractory bleeding from gastrointestinal vascular malformations and are dependent on iron replacement or blood transfusion. Now, in an open-label, randomized trial, researchers in China investigated the efficacy and safety of administering thalidomide in 55 patients with bleeding that was unresponsive or unsuited to treatment by means such as endoscopy, colonoscopy, and double-balloon enteroscopy. Twenty-eight of the participants were transfusion dependent before randomization; 3 with gastric antral vascular ectasia (GAVE) had failed to respond to argon plasma coagulation treatment. Exclusion criteria included portal hypertension, severe comorbidities, peripheral neuropathy, or a history of thromboembolic disease; treatment with steroids, nonsteroidal anti-inflammatory agents, or antiplatelet drugs; or current cancer chemotherapy.


After a 1-year observation period, participants were randomized to receive either 25 mg of thalidomide or 100 mg of iron four times daily for 4 months; they were followed for ?1 year thereafter. Thalidomide recipients did not take iron during the treatment period. Bleeding episodes were determined using a fecal immunochemical test for blood, but clinically relevant endpoints such as blood transfusion and hospitalization were also followed.

During the first year of follow-up, the proportion of patients with a ?50% decrease in bleeding episodes was significantly higher in the thalidomide group than in the iron group (71.4% vs. 3.7%). The decreases in the thalidomide group occurred during the first 8 months of follow-up and were maintained afterward. The thalidomide group also showed a significantly greater decrease in blood-transfusion rates (–78.6% vs. –7.3%), a significantly greater increase in mean hemoglobin level (+3.06 g/dL vs. 0.01 g/dL) and significantly greater decreases in hospitalization rates — both overall and for bleeding. Vascular lesions resolved in the two thalidomide recipients with GAVE but not in the iron recipient with this condition. All the results remained significant in analyses excluding the patients with GAVE.

After the 4-month treatment period, the mean plasma concentration of vascular endothelial growth factor (VEGF) decreased significantly in the thalidomide group (from 118 to 58 pg/mL); the reduction was greater in responders than in nonresponders (–67 vs. –36 pg/mL). Two patients discontinued thalidomide because of leukopenia and somnolence, respectively. Fatigue occurred in more thalidomide recipients than iron recipients (32.1% vs. 11.1%). Neither serious events nor pregnancy occurred in either group during the study.


Citation(s):

Ge Z-Z et al. Efficacy of thalidomide for refractory gastrointestinal bleeding from vascular malformation. Gastroenterology 2011 Jul 25; [e-pub ahead of print].