A New Complication of Thalidomide Therapy

Thalidomide (Thalomid®, Celgene), a drug that was blamed for birth defects years ago, is finding a new respectability as an experimental therapy for various malignancies, including multiple myeloma, gliomas, Kaposi’s sarcoma, and advanced breast cancer. The treatment, however, appears to be dogged by a complication: the more frequent occurrence of venous thromboembolism (VTE). A study of 70 men with advanced andro-gen-independent prostate cancer bears this out.

The men, aged 50 to 80, were given intravenous docetaxel (Taxotere®, Aven-tis) or docetaxel with thalidomide. None of the 23 who received docetaxel alone developed VTE, compared with nine of 47 (19%) who received the combination treatment.
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The researchers could not determine why thalidomide might have a pro-thrombotic effect. The only measured factor that declined appreciably after the initiation of thalidomide/docetaxel therapy—which was not seen in the men taking docetaxel alone—was protein C.

Although the change was statistically significant, it wasn’t great enough to raise the risk of thrombosis; however, it was noted that thalidomide might cause endothelial damage. Agents used in combination with thalidomide that are toxic to the endothelium might be exposing the subendothelial tissue to the pro­thrombotic effect of the anti-angiogenic agent. The authors suggest that thalido-mide and docetaxel, which has anti-angiogenic effects in vitro, might have a synergistic harmful effect.