Thalidomide in Small Cell Lung Cancer: Wrong Drug or Wrong Disease?

Extract

Small cell lung cancer (SCLC) accounts for about 15%–20% of lung cancers, and two-thirds of SCLCs are diagnosed as extensive disease. SCLC is very sensitive to chemotherapy, with initial response rates varying between 70% and 85%. Current standard chemotherapy consists of a combination of a platinum compound with etoposide. Thoracic radiotherapy is recommended in limited disease, as well as prophylactic cranial irradiation in chemotherapy-responding patients, allowing a modest gain in overall survival. However, the vast majority of patients rapidly relapse, develop resistance to therapy, and present an aggressive clinical course. No major therapeutic progress has been achieved in SCLC in the past decade and prognosis remains dismal, with about 11% and 2% survival at 5 years in limited disease and extensive disease, respectively ( 1 ).

Anti-angiogenic therapy is emerging as a new approach in cancer treatment. Bevacizumab, an anti–vascular endothelial growth factor (VEGF) monoclonal antibody, provides progression-free survival benefits when combined with interferon alpha in metastatic renal cancer and in combination with chemotherapy in advanced breast cancer, as well as a survival benefit in colorectal and non–small cell lung cancers, in combination with chemotherapy. VEGF receptor tyrosine kinase inhibitors also prolong survival in renal and hepatic carcinoma ( 2 ). Tumor angiogenesis is expected to play a role in SCLC because VEGF is expressed in approximately 80% of the cancers ( 3 ).