Thalidomide in cancer treatment: a potential role in the elderly?

There is increased interest in the treatment of cancer with thalidomide because of its antiangiogenic, immunomodulating and sedative effects. In animal models, the antitumour activity of thalidomide is dependent on the species, route of administration and coadministration of other drugs. For example, thalidomide has shown antitumour effects as a single agent in rabbits, but not in mice. In addition, the antitumour effects of the conventional cytotoxic drug cyclophosphamide and the tumour necrosis factor inducer 5,6-dimethylxanthenone-4-acetic acid (DMXAA) were found to be potentiated by thalidomide in mice bearing colon 38 adenocarcinoma tumours. Further studies have revealed that thalidomide upregulates intratumoral production of tumour necrosis factor-alpha 10-fold over that induced by DMXAA alone. Coadministration of thalidomide also significantly reduced the plasma clearance of DMXAA and cyclophosphamide. All these effects of thalidomide may contribute to the enhanced antitumour activity. Recent clinical trials of thalidomide have indicated that it has minimal anticancer activity for most patients with solid tumours when used as a single agent, although it was well tolerated. However, improved responses have been reported in patients with multiple myeloma. Palliative effects of thalidomide on cancer-related symptoms have also been observed, especially for geriatric patients with prostate cancer. Thalidomide also eliminates the dose-limiting gastrointestinal toxic effects of irinotecan. There is preliminary evidence indicating that the clearance of thalidomide may be reduced in the elderly. The exact role of thalidomide in the treatment of cancer and cancer cachexia in the elderly remains to be elucidated. However, it may have some value as part of a multimodality anticancer therapy, rather than as a single agent.