Comparative study between daily and 5-days-a-week administration of oral 5-fluorouracil chemotherapy in mice: determining the superior regimen

Background: Oral administration of derivatives of 5-fluorouracil (5-FU) is currently used to treat colorectal cancer in the United States. Oral chemot herapy possesses certain advantages: it is simple. easy to administer. and has few side effects. We compared conventional daily oral administration of 5-FU (daily schedule) with administration on 5 consecutive days followed b y 2 drug-free days (5-days-a-week schedule) in a mouse tumor model. Methods : The maximal tolerated dose (MTD) in the 5-days-a-week schedule and in the daily schedule were determined in 6-week-old nontumor-bearing CDF1 male mi ce. In antitumor experiments. CDF1 mice were inoculated subcutaneously with Colon26 cells (1x10(6) per mouse). Antitumor efficacy was evaluated in ter ms of the ratio of tumor size in treated to control mice (T/C ratio). Resul ts: The MTD of 5-FU in the 5-days-a-week schedule was 42 mg/kg, and in the daily schedule was 29 mg/kg. In the 5-days-a-week schedule dose escalation nearly 1.4 times that in the daily schedule was possible. although the tota l dose over 7 days was similar between the two schedules (203 mg/kg and 210 me;:kg. respectively). When the doses of 5-FU were compared under the cond ition of no body weight loss. the 5-days-a-week schedule produced a compara tive dose escalation of 2.1 times per day (from 20 to 42 mg/kg). and 1.5 ti mes per total weekly amount (from 140 to 210 mg/kg) compared to the daily s chedule. With regard to the antitumor effect as indicated by the T/C ratio. the 5-davs-a-week schedule produced over 70% tumor suppression. whereas th e daily schedule produced only 50% suppression at the MTD. Therapeutic effi cacy was calculated in terms of the ratio of body weight change to antitumo r effect (T/C ratio), and revealed that the MTD of 42 mg/kg 5-FU in the 5-d ays-a-week schedule produced a therapeutic efficacy almost three times that of the MTD of 29 mg/kg 5-FU in the daily schedule (P < 0.001). Conclusions : Using oral administration of 5-FU, we confirmed that the 5-days-a-week sc hedule allowed dose intensity escalation and was superior to the daily sche dule in both enhancement of antitumor effect and protection against adverse effects.