In vitro 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 microM) 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 microM) and CDDP (0-100 microM) or DTIC (250-6,500 microM) were combined in melanoma cell lines. In conclusion, the new nitrosourea S 10036 shows promising activity, particularly against human melanoma cell lines.
Fischel
J L
JL
Centre Antoine Lacassagne, Nice, France.
Formento
P
P
Etienne
M C
MC
Gioanni
J
J
Frenay
M
M
Deloffre
P
P
Bizzari
J P
JP
Milano
G
G
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002330:Carmustine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D003606:Dacarbazine / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D008130:Lomustine / Q000494:pharmacology; D008545:Melanoma / Q000473:pathology; D009607:Nitrosourea Compounds / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; D008130:Lomustine; D003606:Dacarbazine; C054368:fotemustine; D002945:Cisplatin; D002330:Carmustine; D013936:Thymidine