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 (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-alpha, bFGF, VEGF, IL-6 and IL-12 before and during treatment. In patients with SD > or = 3 months or an objective response, a statistically significant decrease in serum TNF-alpha levels was demonstrated (P = 0.05). The commonest toxicities were lethargy (> or = grade II, 10 patients), constipation (> or = grade II, 11 patients) and neuropathy (> or = 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.
Stebbing
J
J
Department of Medical Oncology, The Royal Marsden Hospital, London SW3 6JJ, UK.
Benson
C
C
Eisen
T
T
Pyle
L
L
Smalley
K
K
Bridle
H
H
Mak
I
I
Sapunar
F
F
Ahern
R
R
Gore
M E
ME
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D003248:Constipation / Q000139:chemically induced; D016207:Cytokines / Q000097:blood; D018450:Disease Progression; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D012894:Sleep Stages; D013792:Thalidomide / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D016207:Cytokines; D013792:Thalidomide