ANTITUMOR-ACTIVITY OF TREOSULFAN IN HUMAN LUNG CARCINOMAS

Treesulfan (L-threitol 1,4-bismethanesulfonate, Ovastat) is an alkylat ing agent and a structural analogue of busulfan. It has been establish ed in the clinical chemotherapy of human ovarian carcinomas for severa l years and has additionally been shown to be effective against xenogr afted human breast carcinomas. No other human carcinoma is yet known t o be sensitive to treosulfan. The present study confirms the pronounce d and significant antitumor activity of treosulfan against heterotrans planted 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 cytostati cs ifosfamide, cisplatin, and etoposide toward three of them and induc ed long-lasting growth reductions (60-98% of control tumor size) corre sponding 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, mitomy cin C, and cisplatin at least in one of four epidermoid lung carcinoma s, one large-cell carcinoma, and one of three lung adenocarcinomas. Th ese results are remarkable and unexpected, and the present study shoul d be followed rapidly by phase II clinical trials of treosulfan agains t human lung carcinomas of both the small-cell and the non-small-cell type.