Thalidomide for the treatment of severe intestinal bleeding

The interesting observations of Alberto et al. extend our findings in patients with multiple angiodysplasias [1], and further supports existing literature that thalidomide provides an effective therapy for recurrent bleeding related to vessel malformations within the gastrointestinal system. In cases like the one presented, hormonal therapy is commonly employed. However, a large randomized study in patients with angiodysplasias demonstrated that hormonal therapy is ineffective in this clinical setting [2]. Although the results of this study do not completely rule out that there may be some efficacy of hormones in Osler’s disease, the therapeutic potential of hormonal therapy is obviously limited.

Despite a distinct pathophysiology of vessel malformation in angiodysplasia and Osler’s disease, both are characterized by activated vascular endothelial growth factor (VEGF)-mediated angiogenesis. Local overexpression of VEGF results in the formation of incomplete and dysfunctional endothelial vessels, which lack a smooth muscle layer, are instable and susceptible to rupture. Therefore, inhibition of VEGF-mediated angiogenesis proves a causal therapy. Together with increasing evidence of clinical efficacy in bleeding related to angiodysplasia and Osler’s disease, thalidomide was recently also reported to be effective in a case of severe irradiation-induced hemorrhagic proctitis [3].

However, thalidomide is also teratogenic. In women of childbearing potential the substance will clearly remain a rescue therapy for severe cases, and requires strict surveillance. Contraception by two methods is mandatory during thalidomide treatment. In young women, therefore, hormonal therapy (which consists of standard contraception preparations) will still have a chance as a first treatment option. In male and infertile female patients, however, thalidomide may serve as first-line therapy. In these patients neurotoxicity (commonly reversible peripheral neuropathy) is the most important side-effect, which requires pretreatment neurologic evaluation and monitoring during therapy.

Taken together, thalidomide provides a promising new treatment option for different causes of gastrointestinal bleeding. However, further studies are necessary to evaluate the optimal dose and duration of thalidomide therapy.

Competing interests: None

References

• 1 Bauditz J, Lochs H, Voderholzer W. Macroscopic appearance of intestinal angiodysplasias under antiangiogenic treatment with thalidomide.  Endoscopy. 2006;  38 1036-1039
• 2 Junquera F, Feu F, Papo M. et al . A multicenter, randomized, clinical trial of hormonal therapy in the prevention of rebleeding from gastrointestinal angiodysplasia.  Gastroenterology. 2001;  121 1073-1079
• 3 Craanen M E, vanTriest B, Verheijen R H, Mulder C J. Thalidomide in refractory haemorrhagic radiation induced proctitis.  Gut. 2006;  55 1371-1372