INVITRO CHEMOSENSITIVITY TESTING OF FOTEMUSTINE (S-10036), A NEW ANTITUMOR NITROSOUREA

Fotemustine (S 10036) is a new anti-tumor nitrosourea characterized by a phosphonoalanine carrier group coupled to the nitrosourea moiety, which potentially increases the cellular penetration of the drug. Using human tumor cell lines, the activity of S 10036 was compared with that of the more established nitrosoureas BCNU and CCNU. Growth-inhibiting effects were evaluated by the [3H]-thymidine incorporation test. In a panel of 12 human cancer cell lines [melanoma (4), ovary (2), head and neck (3), lung (1), bladder (1), breast (1)], the dose-response curves of S 10036 (0-100 μM) were similar to those obtained with equimolar concentrations of BCNU and CCNU; they indicated a moderately more marked effect for two and an equal effect for six melanoma cell lines with S 10036 as compared with BCNU. Moderate but significant synergistic combinations were obtained when S 10036 (0-80 μM) and CDDP (0-100 μM) or DTIC (250-6,500 μM) were combined in melanoma cell lines. In conclusion, the new nitrosourea S 10036 shows promising activity, particularly against human melanoma cell lines. © 1990 Springer-Verlag.