TREOSULFAN SHOWS CYTOTOXIC EFFECT ON SPHEROIDS FROM PRIMARY-CELL CULTURES OF KIDNEY-CELL CARCINOMAS INDEPENDENTLY OF P-GLYCOPROTEIN EXPRESSION

Therapy of advanced renal cell carcinoma remains difficult. New thera peutic schemes besides cytokine treatment should be evaluated. The fol lowing study analyzes the in vitro toxicity of treosulfan on spheroids of 8 primary cultures of renal cell carcinoma cells. These data were compared to the toxicity of vinblastine. All investigations were perfo rmed in regard to the P-glycoprotein (Pgp) expression of the cells, wh ich is one of the main causes of multidrug resistance. Four Pgp positi ve and four Pgp negative spheroids were incubated with the drugs in in creasing doses. Toxicity was measured using the MTT toxicity assay as well as trypan blue exclusion. Significantly higher toxicity of treosu lfan compared to vinblastine could be demonstrated. In addition, the e ffects of treosulfan were not related to Pgp expression. These results are encouraging and a phase II study analyzing the efficacy of treosu lfan in patients with advanced renal cell carcinoma has been initiated in our institution.