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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-α, basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6). The resulting anti-angiogenic, immunomodulatory and growth suppressive effects fo...

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Detalles Bibliográficos
Autores principales: Stebbing, J, Benson, C, Eisen, T, Pyle, L, Smalley, K, Bridle, H, Mak, I, Sapunar, F, Ahern, R, Gore, M E
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2001
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2375104/
https://www.ncbi.nlm.nih.gov/pubmed/11592764
http://dx.doi.org/10.1054/bjoc.2001.2025
Descripción
Sumario:Thalidomide is reported to suppress levels of several cytokines, angiogenic and growth factors including TNF-α, basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6). The resulting anti-angiogenic, immunomodulatory and growth suppressive effects form the rationale for investigating thalidomide in the treatment of malignancies. We have evaluated the use of high-dose oral thalidomide (600 mg daily) in patients with renal carcinoma. 25 patients (all men; median age, 51 years; range 34–76 years) with advanced measurable renal carcinoma, who had either progressed on or were not suitable for immunotherapy, received thalidomide in an escalating schedule up to a maximum dose of 600 mg daily. Treatment continued until disease progression or unacceptable toxicity were encountered. 22 patients were assessable for response. 2 patients showed partial responses (9%; 95% CI: 1–29), 7 (32%; 95% CI: 14–55) had stable disease for more than 6 months and a further 5 (23%; 95% CI: 8–45) had stable disease for between 3 and 6 months. We also measured levels of TNF-α, bFGF, 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 serum TNF-α levels was demonstrated (P = 0.05). The commonest toxicities were lethargy (≥ grade II, 10 patients), constipation (≥ grade II, 11 patients) and neuropathy (≥ grade II, 5 patients). Toxicities were of sufficient clinical significance for use of a lower and well tolerated dose of 400 mg in currently accruing studies. © 2001 Cancer Research Campaignhttp://www.bjcancer.com