Antitumor efficacy of combination chemotherapy with UFT and cyclophosphamide against human breast cancer xenografts in nude mice

The combination of cyclophosphamide (CPA) and 5-fluorouracil (5-FU) is curr ently regarded as the most effective therapy for the treatment of patients with advanced and recurrent breast cancer. We evaluated the augmentation of antitumor activity and toxicity by coadministration of CPA and UFT (1M teg afur - 4M uracil) instead of intravenous 5-FU on H-31 human breast cancer x enografts in nude mice. The maximum tolerable dose (MTD) of UFT alone (24 m g/kg) and CPA alone (85 mg/kg) had a significant effect On H-31 tumors in m ice with 86.6% and 83.0% inhibition rates of tumor growth, respectively, an d without loss of body weight, diarrhea or myelosuppression. The combined a dministration with full and 83.3% MTD of LIFT and CPA augmented the antitum or activity compared to that of UFT alone and CPA alone. The relative tumor volume of the UFT plus CPA -treated group to the UFT- and CPA-treated grou ps was 0.28 and 0.36 for the frill MTD, and 0.51 and 0.67 for 83.3% MTD, re spectively. When CPA was consecutively administered to the tumor-bearing mi ce for 14 days, there were no decreases in the activities of enzymes relate d to 5-FU metabolism but there was an significant increase in the activity of ribonucleotide reductase, suggesting that anabolism of 5-FU derived from tegafur is accelerated to some extent by coadministration of CPA. In concl usion, these results suggest that combination therapy with oral UFT and CPA may be useful for the long-term treatment of cancer patients with advanced and recurrent breast cancers.