Randomized comparative study of surgical adjuvant chemotherapy using 5-fluorouracil and dl-leucovorin with CDDP, 5-FU and dl-leucovorin for advanced colorectal cancer

BACKGROUND: 5-fluorouracil (5-FU) is the most useful chemotherapeutic agent for colorectal carcinoma. Recently, the effectiveness of multidrug therapy in modifying the anticancer activity of 5-FU for advanced cases was clarified. We conducted a randomized comparative study of surgical adjuvant chemotherapy comparing cis-diamminedichloroplatinum (CDDP), 5-FU and dl-leucovorin (LV) (PFL therapy) with dl-LV and 5-FU (FL therapy) in patients who underwent curative resection of stage II and III colorectal carcinoma. METHODS: Thirty-one patients, 13 ungergoing PFL therapy and 18 undergoing FL therapy, completed the scheduled administration, while 20 dropped out. Administration schedules were as follows: PFL therapy consisted of 13 mg/m2 CDDP, 300 mg/m2 5-FU and 30 mg/body weight LV for 5 consecutive days. The FL therapy consisted of 300 mg/m2 5-FU and 30 mg/body weight LV for 5 consecutive days in hospital. Both regimens were followed by biweekly administration of the same dosages of LV and 5-FU in an outpatient setting. RESULTS: Seven of 23 patients in the PFL therapy group and five of 28 patients in the FL therapy group experienced recurrence of colorectal carcinomas. Regarding prognosis of stage II patients, both groups showed similar results in 5-year disease specific survival and disease-free survival. However, stage III patients obtained better prognostic results in the FL therapy group than in the PFL therapy group. Major toxicities in these regimens were vomiting and leukopenia, both being more frequent in the PFL therapy group. Symptoms of toxicity resolved completely in all patients. CONCLUSION: From the present study we found that PFL therapy brought no benefit for stage II and III colorectal carcinoma compared with FL therapy. We should search for more appropriate adjuvant therapy, increasing the therapeutic effect of 5-FU + LV for stage II and III colorectal carcinoma.