Sequence-dependent activity of 5-fluorouracil plus tauromustine in a transplantable well-differentiated murine colon adenocarcinoma.

Previous in vitro studies with 5-Fluorouracil (5-FU) plus Tauromustine (TCNU) demonstrated sequence-dependent effects. This study extended these investigations into an in vivo experimental model, relevant to clinical disease. A transplantable murine adenocarcinoma of the colon, MAC 29, was shown to have stable histology and reproducible growth. This model was used to determine the influence of sequence of administration of this drug combination. Effects ranged from antagonism, with 5-FU given 24 hours before TCNU, to addition, simultaneous treatment, and synergism, 5-FU 24 hours after TCNU. Careful consideration of sequence should be made during the evaluation of this combination in clinical trials.