The treatment of advanced renal cell cancer with high-dose oral thalidomide

Thalidomide is reported to suppress levels of several cytokines, angiogenic and growth factors including TNF-alpha, basic fibroblast growth factor (bF GF), vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6). Th e resulting anti-angiogenic, immunomodulatory and growth suppressive effect s form the rationale for investigating thalidomide in the treatment of mali gnancies. We have evaluated the use of high-dose oral thalidomide (600 mg d aily) in patients with renal carcinoma. 25 patients (all men; median age, 5 1 years; range 34-76 years) with advanced measurable renal carcinoma, who h ad either progressed on or were not suitable for immunotherapy, received th alidomide in an escalating schedule up to a maximum dose of 600 mg daily. T reatment continued until disease progression or unacceptable toxicity were encountered. 22 patients were assessable for response. 2 patients showed pa rtial responses (9%; 95% CI: 1-29), 7 (32%; 95% Cl: 14-55) had stable disea se for more than 6 months and a further 5 (23%; 95% Cl: 8-45) had stable di sease for between 3 and 6 months. We also measured levels of TNF-alpha, bFG F, VEGF, IL-6 and IL-12 before and during treatment. In patients with SD 3 months or an objective response, a statistically significant decrease in se rum TNF-alpha levels was demonstrated (P = 0.05). The commonest toxicities were lethargy (greater than or equal to grade II, 10 patients), constipatio n (a grade II, 11 patients) and neuropathy ( !: grade 11, 5 patients). Toxi cities were of sufficient clinical significance for use of a lower and well tolerated dose of 400 mg in currently accruing studies. (C) 2001 Cancer Re search Campaign http://www.bjcancer.com.