Use of mathematical models for the evaluation of two- and three-drug combination chemotherapy in murine tumor models.
In parallel with an ongoing clinical trial in patients with metastatic mammary carcinoma, we compared the three-drug combination of cyclophosphamide, tegafur, and methotrexate with the two-drug combination of cyclophosphamide and tegafur in the murine L1210 leukemia and B16 melanoma models. The obtained data based on a central composite design were calculated by mathematical models, which estimate optimum dose combinations for survival by restricting side effect constraints (loss of weight, leukopenia). The main results were as follows: (a) long-term survival can be reached only by accepting a relatively high toxicity in each case, and (b) in the L1210 model the three-drug combination was superior to the two-drug combination, while in the B16 melanoma cyclophosphamide as a single agent offered the best results. The experimental yields are in accordance with preliminary results of the clinical trial. The mathematical model used offers the possibility of comparing drug combinations in a relatively economic way.
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D008433:Mathematics; D051379:Mice; D008815:Mice, Inbred Strains; D008954:Models, Biological; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000401:mortality
D000970:Antineoplastic Agents