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.