Antitumor activity of 2-chloroethyl (methylsulfonyl)methanesulfonate (clomesone, NSC 33847) against selected tumor systems in mice.
Clomesone was evaluated for antitumor activity against a spectrum of animal tumor models. Clomesone exhibited significant antitumor activity against the murine L1210 leukemia implanted i.p., s.c., and intracerebrally (i.c.). Activity against s.c.-implanted tumor was largely independent of schedule and route of administration. Therapeutically optimal single-dose treatment (for tumored mice) was less toxic to nontumored mice than therapeutically optimal prolonged treatment. Clomesone also exhibited activity against other murine tumors (P388 leukemia, B16 melanoma, Lewis lung carcinoma, and M5076 sarcoma). It was active against P388 leukemia sublines resistant to cyclophosphamide, L-phenylalanine mustard, and cis-diamminedichloroplatinum(II). No activity was observed against a P388 subline resistant to N,N'-bis(2-chloroethyl)-N-nitrosourea or against Ridgway osteogenic sarcoma, a nitrosourea-resistant murine solid tumor. Clomesone is generally as effective as the chloroethylnitrosoureas against experimental tumor models. Since clomesone does not have the hydroxyethylating and carbamoylating activities of the chloroethylnitrosoureas (which do not appear to contribute to antitumor activity), it would likely be a more toxicologically selective compound. It may prove to be less carcinogenic than the chloroethylnitrosoureas, and it may contribute less target organ toxicity and less interference with the actions of other drugs when used in combinations.
Dykes
D J
DJ
Southern Research Institute, Birmingham, Alabama 35255-5305.
Waud
W R
WR
Harrison
S D
SD
Laster
W R
WR
Griswold
D P
DP
Shealy
Y F
YF
Montgomery
J A
JA
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004249:DNA Damage; D004351:Drug Resistance; D005038:Ethylnitrosourea / Q000031:analogs & derivatives / Q000494:pharmacology; D008698:Mesylates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000188:drug therapy*
D000970:Antineoplastic Agents; D008698:Mesylates; C017139:1-(2-chloroethyl)-1-nitrosourea; C041189:clomesone; D005038:Ethylnitrosourea