Thalidomide in cancer.
Thalidomide has immunomodulatory and anti-angiogenic properties which may underlie its activity in cancer. After its success in myeloma, it has been investigated in other plasma cell dyscrasias, myelodysplastic syndromes, gliomas, Kaposi's sarcoma, renal cell carcinoma, advanced breast cancer, and colon cancer. Thalidomide causes responses in 30-50% of myeloma patients as a single agent, and acts synergistically with corticosteroids and chemotherapy. Thalidomide results in the reduction or elimination of transfusion-dependence in some patients with myelodysplastic syndrome. Responses have also been seen in one-third of patients with Kaposi's sarcoma, in a small proportion of patients with renal cell carcinoma and high-grade glioma, and in some patients with colon cancer in combination with irinotecan. The drug is being investigated currently in a number of clinical trials for cancer. Drowsiness, constipation, and fatigue are common side effects, whereas peripheral neuropathy and skin rash are seen in one-third. A minority of patients experience bradycardia. Thrombotic phenomena are especially common when thalidomide is combined with chemotherapy. Adverse effects severe enough to necessitate cessation of therapy are seen in around 20% of patients. A therapeutic trial of thalidomide is essential in all patients with relapsed or refractory myeloma. In other cancers, the best way to use the drug is in the setting of clinical trials. In the absence of access to studies or alternative therapeutic options, thalidomide could be considered singly or in combination with standard therapy.
Singhal
S
S
Division of Hematology/Oncology, Northwestern University Medical School and The Robert H. Lurie Cancer Center of Northwestern University, Chicago, IL 60611, USA. s-singhal@northwestern.edu
Mehta
J
J
D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001919:Bradycardia / Q000139:chemically induced; D005076:Exanthema / Q000139:chemically induced; D006801:Humans; D007376:Interleukin-2 / Q000037:antagonists & inhibitors; D009369:Neoplasms / Q000188:drug therapy*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D013792:Thalidomide / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D013927:Thrombosis / Q000139:chemically induced; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D000093242:Interleukin-6 Inhibitors
D020533:Angiogenesis Inhibitors; D007376:Interleukin-2; D013792:Thalidomide; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors