Continuous low dose Thalidomide: a phase II study in advanced melanoma, renal cell, ovarian and breast cancer

To grow and metastasize, solid tumours must develop their own blood supply by neo-angiogenesis. Thalidomide inhibits the processing of mRNA encoding p eptide molecules including tumour necrosis factor-alpha (TNF-alpha) and the angiogenic factor vascular endothelial growth factor (VEGF). This study in vestigated the use of continuous low dose Thalidomide in patients with a va riety of advanced malignancies. Sixty-six patients (37 women and 29 men; me dian age, 48 years; range 33-62 years) with advanced measurable cancer (19 ovarian. 18 renal, 17 melanoma. 12 breast cancer) received Thalidomide 100 mg orally every night until disease progression or unacceptable toxicity wa s encountered. Three of 18 patients with renal cancer showed partial respon ses and a further three patients experienced stabilization of their disease for up to 6 months. Although no objective responses were seen in the other tumour types, there were significant improvements in patients' sleeping (P < 0.05) and maintained appetite (P < 0.05). Serum and urine concentrations of basic fibroblast growth factor (bFGF), TNF-alpha and VEGF were measured during treatment and higher levels were associated with progressive diseas e. Thalidomide was well tolerated: Two patients developed WHO Grade 2 perip heral neuropathy and eight patients developed WHO grade 2 lethargy. No pati ents developed WHO grade 3 or 4 toxicity. Further studies evaluating the us e of Thalidomide at higher doses as a single agent for advanced renal cance r and in combination with biochemotherapy regimens are warranted. (C) 2000 Cancer Research Campaign.