Optimal treatment schedule and antitumor spectrum of 4-carbamoylimidazolium 5-olate (SM-108) in murine tumors
Yoshida, N.; Nakamura, M.; Fukui, M.; Morisada, S.; Ogino, S.; Inaba, M.; Tsukagoshi, S.; Sakurai, Y.
Cancer Research 43(12 Part 1): 5851-5856
1983
ISSN/ISBN: 0008-5472 PMID: 6640536 Document Number: 216045
By designing optimal administration schedules, it was found that 4-carbamoylimidazolium 5-olate (SM-108) showed an excellent antitumor potency against a number of murine tumors. The optimal administration schedule of SM-108 was an intermittent multiple administration, in which the drug was multiply administered to mice at definite intervals of less than 3 hr for about 1 day on Days 1, 5, and 9 following tumor implantation. Although usual daily administration of SM-108 exhibited poor efficacy, the intermittent multiple administration of SM-108 exhibited potent antitumor activity against a wide variety of tumors, such as Ehrlich carcinoma, P388, 6-mercaptopurine-sensitive and -resistant L1210, Lewis lung carcinoma, Colon 26 adenocarcinoma, and Sarcoma 180. Among them, Ehrlich carcinoma showed the most prominent susceptibility to SM-108. With the intermittent multiple administration of SM-108, complete suppression was obtained in both the ascitic and solid forms of this tumor over a wide dose range. The schedule dependency of the antitumor effect of SM-108 described above was reasonably explained by its in vitro growth-inhibitory effects and pharmacokinetics in the mice.