Efficacy of long-term combination chemotherapy of cyclophosphamide (CPA) and 5'-deoxy-5-fluorouridine (5'-DFUR), both of which have been widely used as chemotherapeutics against breast cancer patients, was examined in a mammary tumor xenograft model, MX-1. 5'-DFUR suppressed the tumor growth over a long period and prolonged the survival, although it did not reduce the initial tumor burden, CPA induced the disappearance of the tumor burden temporarily. However, CPA became inaffective despite continuation of treatment, and induced the recurrence of the tumor. The combination of these two drugs dramatically reduced the tumor burden, and suppressed the recurrence of the tumor over a long period. The tumor recurring during CPA monotherapy was resistant to CPA but susceptible to 5'-DFUR, which could be a reason for the long-lasting activity of the combination therapy. These results indicate that CPA and 5'-DFUR monotherapies have different modes of antitumor activities in the long-term therapy model, and that these drugs in combination would have better therapeutic advantage than each drug given individually.

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