Treosulfan (L-threitol-1,4-bismethanesulfonate, Ovastat) was tested on human renal
tumor cells growing as xenografts in athymic nude mice and as monolayers in vitro, in comparison with clinically used
cytostatic drugs (in vivo,
cyclophosphamide,
vinblastine, and
5-fluorouracil; in vitro,
vinblastine and 5-fluoro-2'-
deoxyuridine) which were administered at equitoxic or equivalent dose levels, respectively. Four human renal
tumor xenografts (N-U 2, N-U 26, MRI-H 121, KTCTL-1M) were investigated in vivo, and seven renal tumor cell lines (KTCTL-1M, KTCTL-2, KTCTL-26A, KTCTL-30, KTCTL-84, MRI-H 121, N-U 2) under in vitro conditions. The investigations of the four human renal
tumor xenografts revealed that
treosulfan is capable of inducing pronounced growth inhibitions ranging from 60-100% in comparison with untreated control
tumors. In the xenografted
renal-cell carcinoma KTCTL-1M,
treosulfan administered at the highest dose level (1 x 3,500 mg/kg) even effected a complete remission lasting for more than three weeks in all animals treated with this dose. It was more effective in the N-U 2
carcinoma growing in vivo than the comparative compounds
cyclophosphamide and
vinblastine. In the heterotransplanted
renal-cell carcinoma N-U 26,
treosulfan showed a similar activity as the two established
cytostatic drugs tested whereas, in the renal
sarcoma MRI-H 121, both
cyclophosphamide and
vinblastine were slightly more effective than
treosulfan. In four
renal-cell carcinomas growing as monolayers in vitro (KTCTL-1M, KTCTL-2, KTCTL-84, N-U 2),
treosulfan induced cell growth inhibitions by about 50% at peak plasma concentration in comparison with untreated control cultures. The IC50 values ranged from 5 x 10(-6) to 10(-4) mol/l in all seven monolayer cultures investigated
5-Fluoro-2'-deoxyuridine (
floxuridine) was similarly active in vitro as
treosulfan with respect to the molar concentrations inducing growth inhibition and to the IC50 values, whereas
vinblastine was more effective than
treosulfan in most of the human renal
tumor cell monolayers investigated. These results reveal the remarkable antitumor efficacy of
treosulfan towards human
renal-cell carcinomas, especially under in vivo conditions. This activity was similarly high or even better than in
cyclophosphamide and
vinblastine. The in vitro data obtained in monolayer cultures also confirmed the remarkable antiproliferative activity of
treosulfan in renal
tumor cells, but did not mirror very well the pattern of antitumor activity observed in vivo.