Antitumor activity of treosulfan in human lung carcinomas

Treosulfan (L-threitol 1,4-bismethanesulfonate, Ovastat) is an alkylating agent and a structural analogue of busulfan. It has been established in the clinical chemotherapy of human ovarian carcinomas for several years and has additionally been shown to be effective against xenografted human breast carcinomas. No other human carcinoma is yet known to be sensitive to treosulfan. The present study confirms the pronounced and significant antitumor activity of treosulfan against heterotransplanted human lung carcinomas of both the small-cell and the non-small-cell type. Treosulfan reduced the growth of all four small-cell lung carcinomas that were investigated in a significant manner. It was even more active than equitoxic doses of the clinically approved cytostatics ifosfamide, cisplatin, and etoposide toward three of them and induced long-lasting growth reductions (60-98% of control tumor size) corresponding to partial and nearly complete remissions. In the case of the nine non-small-cell lung carcinomas investigated, treosulfan effected significant growth inhibition of more than 50%, again in all of them, and was more active than the comparative compounds ifosfamide, mitomycin C, and cisplatin at least in one of four epidermoid lung carcinomas, one large-cell carcinoma, and one of three lung adenocarcinomas. These results are remarkable and unexpected, and the present study should be followed rapidly by phase II clinical trials of treosulfan against human lung carcinomas of both the small-cell and the non-small-cell type.