Gastroenterology

Gastroenterology

Volume 141, Issue 5, November 2011, Pages 1629-1637.e4
Gastroenterology

Original Research
Clinical—Alimentary Tract
Efficacy of Thalidomide for Refractory Gastrointestinal Bleeding From Vascular Malformation

https://doi.org/10.1053/j.gastro.2011.07.018Get rights and content

Background & Aims

Patients with recurrent bleeding from gastrointestinal vascular malformations are a challenge to treat. We investigated the long-term efficacy and safety of thalidomide for refractory bleeding from gastrointestinal vascular malformations in an open-label, randomized study.

Methods

Eligible patients were randomly assigned to groups that were given either 100 mg thalidomide (n = 28) or 400 mg iron (n = 27, controls), daily for 4 months; patients were followed for at least 1 year (mean, 39 months). Bleeding was defined by a positive result from an immunoassay fecal occult blood test. The primary end point was the effective response rate, defined as the proportion of patients in whom bleeding episodes had decreased by ≥50% in the first year of the follow-up period. The secondary end points included the rates of cessation of bleeding, blood transfusion, overall hospitalization, and hospitalization for bleeding. We also quantified yearly bleeding episodes, bleeding duration, levels of hemoglobin, and yearly requirements for transfusions of red cells, numbers of hospitalizations for bleeding, and hospital stays. Plasma levels of vascular endothelial growth factor were measured in the group given thalidomide.

Results

Rates of response in the thalidomide and control groups were 71.4% and 3.7%, respectively (P < .001). All secondary end points differed significantly different between groups; thalidomide was more effective. No severe adverse effects were observed, although minor side effects were common among patients in the thalidomide group. Levels of vascular endothelial growth factor were significantly reduced by thalidomide (P < .001).

Conclusions

Thalidomide is an effective and relatively safe treatment for patients with refractory bleeding from gastrointestinal vascular malformations. Mechanisms of thalidomide activity might involve vascular endothelial growth factor.

Section snippets

Study Population

Consecutive patients who were diagnosed with GIVM at the Department of Gastroenterology, Renji Hospital, from November 2003 to November 2007 were eligible for the screening for the study.

Patients must have met the following inclusion criteria to enter the study: (1) patients were between 40 and 85 years old; (2) female patients were postmenopausal, with post-tubal ligation, or females with childbearing potential using some form of birth control (eg, contraceptive ring or latex condoms); (3)

Demographical and Clinical Characteristics

A total of 80 patients confirmed as having GIVM were screened and 2 patients who did not complete the 1-year observation were excluded from the study. Thus, 78 patients were enrolled and completed the 1-year observation, during which 19 patients had <6 bleeding episodes and 59 had ≥6 bleeding episodes. Of these 59 patients eligible for randomization, 2 developed severe concomitant diseases and had to be withdrawn and another 2 patients refused to continue. Fifty-five patients were finally

Discussion

This exploratory study showed that thalidomide is an effective and relatively safe therapy preventing recurrent bleeding as defined by positive iFOBT test due to GIVM, with an effective response rate of 71.4% (20 of 28), whereas the rate was 3.7% (1 of 27) in the iron-controlled group (intention-to-treat; P < .001) within 1-year follow-up. The rate of bleeding cessation was significantly higher in the thalidomide group than in the iron-controlled group (46.4% vs 0%; P < .001) during the whole

Conclusions

Thalidomide is effective and relatively safe for refractory bleeding from GIVM. Mechanisms of thalidomide activity might involve VEGF.

Acknowledgments

Drs Zhi-Zheng Ge and Hui-Min Chen contributed equally to this paper.

All procedures were in accordance with the Declaration of Helsinki. Informed consent was taken from all patients and the Institute Ethics Committee approved the study protocol. The full trial protocol can be accessed from Dr. Zhi-Zheng Ge via email to [email protected].

The name of trial registry is “Long-term Effects of Thalidomide for Recurrent Gastrointestinal Bleeding Due to Vascular Malformation.” The Registration

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    Conflicts of interest The authors disclose no conflicts.

    Funding The study was not supported by any pharmaceutical funding. The study medications were provided by the Pharmacy Department of Renji Hospital. All data and analyses were conducted at Renji Hospital.

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