Tauromustine is more effective than conventional chemotherapy in the treatment of colonic tumors.
Despite recent advances in chemotherapy, the prognosis of advanced colorectal cancer remains poor. Although the taurine-based nitrosourea tauromustine (TCNU) has demonstrated schedule-dependent synergism with 5-fluorouracil (5-FU) and leucovorin (LV) against a variety of tumors in vitro, its efficacy relative to and in combination with these drugs in vivo remains unknown. To study this, BALB/C mice had C26 tumor implanted subcutaneously five days prior to the following treatment (doses and route of administration being the same in all groups): Group 1--no treatment; Group 2--TCNU (30 mg/kg by gavage); Group 3--LV (100 mg/kg intraperitoneally [IP]) and, one hour later, LV plus 5-FU (100 mg/kg IP); Group 4--LV and, one hour later, LV plus 5-FU and TCNU; and Group 5--TCNU and, on the following day, LV and, one hour later, LV plus 5-FU. All treatments were repeated seven days later. Body weight and tumor weight were measured twice weekly, and survival was noted. Postmortems were performed in all animals, and evidence of primary or secondary tumor was recorded. All surviving animals were sacrificed at 60 days. We found that 1) 87 percent of animals receiving TCNU and 60 percent of animals receiving LV, 5-FU, and TCNU survived to day 60; none of these animals had evidence of tumor when sacrificed; 2) animals in all other groups died by day 34; 3) evidence of metastases was found in five animals in Group 1 and one each in Groups 2 and 5; and 4) administering TCNU 24 hours prior to 5-FU plus LV resulted in death from toxicity in all animals. Thus, while synergism between TCNU and 5-FU plus LV was not seen, the antitumor properties of TCNU are significantly greater than those of conventional chemotherapy.
Singh
G
G
Department of Surgery, Michigan State University, East Lansing 48824.
Graffner
H O
HO
Milsom
J W
JW
Chaudry
I H
IH
D000818:Animals; D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents / Q000627:therapeutic use* / Q000633:toxicity; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005472:Fluorouracil / Q000627:therapeutic use; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009607:Nitrosourea Compounds / Q000627:therapeutic use* / Q000633:toxicity; D013654:Taurine / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D013654:Taurine; C052991:1-(2-chloroethyl)-3-(2-(dimethylaminosulfonyl)ethyl)-1-nitrosourea; D002955:Leucovorin; D005472:Fluorouracil