[Thalidomide. Clinical trials in cancer].
The breakthrough discovery of the anti-angiogenic effects of thalidomide gave impetus to a series of clinical trials in patients with solid tumors and hematologic malignancies. Thalidomide has been shown to block the activity of angiogenic substances like bFGF, VEGF and interleukin 6. This drug also down-regulates TNF alpha. Thalidomide has shown clinical antitumor activity in single-agent, phase II clinical trials in AIDS-related Kaposi sarcoma, glioma, multiple myeloma refractory to chemotherapy, and hormone-refractory prostate cancer. In contrast, thalidomide was inactive in breast, lung and kidney cancer. The dose-limiting toxicity of thalidomide is sedation. Other adverse effects include skin rash, constipation, dry mouth and liver function abnormalities, along with peripheral neuropathy and the drug's well-known teratogenic potential. The advantages of thalidomide include the convenience of the oral route of administration, the drug's toxicity profile--substantially milder than that of chemotherapy--and its low cost. The potential role of thalidomide in the treatment of human neoplasia will be confirmed by means of randomized clinical trials.
Politi
P M
PM
II Cátedra de Farmacología, Facultad de Medicina, Universidad de Buenos Aires. politi@ciudad.com.ar
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy; D008297:Male; D009101:Multiple Myeloma / Q000188:drug therapy; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D011471:Prostatic Neoplasms / Q000188:drug therapy; D012514:Sarcoma, Kaposi / Q000188:drug therapy; D013792:Thalidomide / Q000627:therapeutic use*
D020533:Angiogenesis Inhibitors; D013792:Thalidomide