RESUMEN
PURPOSE: To evaluate the effectiveness of 6-month therapy with leucovorin (LV)+5-fluorouracil (5-FU) versus 12-month therapy with levamisole (LVS)+5-FU, as adjuvant chemotherapy in patients with completely resected Aster-Coller stage B(2) or C(1)/C(2) rectal cancer (RC). PATIENTS AND METHODS: One hundred and fifty patients with surgically resected RC were enrolled. Seventy patients with stage B(2) and 80 with stage C were randomly assigned to adjuvant chemotherapy with 5-FU+LXx6 months or 5-FU+LVSx12 months. Patient characteristics were equally balanced between the examined groups. Adjuvant chemotherapy consisted of LV 20 mg/m(2) intravenously (i.v.) plus 5-FU 450 mg/m(2) i.v. bolus every week plus LVS tablets 50 mg t.i.dx3 days every 2 weeks for 1 year. RESULTS: After a median follow up for survivors of 8.7 years (range 1.8-10.5), all of the patients were evaluable. There were no significant differences between the two treatment groups with respect to the recurrence rates (p=0.821). Moreover, there were no significant differences between the two tratment groups in disease-free survival (DFS) (p=0.84) [B(2)(p=0.805) and C (p=0.978)] and overall survival (OS) rates for patients of either stage B(2) or C (p=0.78). Toxicities were more frequent in the 5-FU+LVS versus 5-FU+LV group: myelosuppression (grade 3 leucopenia, 12 versus 4%, p<0.04), diarrhea (grade 0, 60 versus 76%, p<0.02), and liver toxicity (increase of transaminases >3-fold, 12 patients versus 2, p<0.03.). No patient stopped chemotherapy because of toxicity, and there were no treatment-related deaths. CONCLUSION: Adjuvant chemotherapy in RC with LV+5-FU for 6 months is equally effective and less toxic than LVS+5-FU for 12 months.
RESUMEN
The aim of this study was to evaluate the effectiveness of 6-month therapy with leucovorin (LV) + 5-fluorouracil (5-FU) vs 12 months of therapy with levamisole (LVZ) + 5-FU, as adjuvant chemotherapy in patients with completely resected Dukes' stage B2 or C rectal cancer. One hundred and fifty patients with surgically resected rectal carcinoma, were enrolled in the present study; Dukes' stage B2 (n=70) or C (n=80), were randomly assigned to chemotherapy with 5-FU + LV x 6 months or 5-FU + LVZ x 12 months. Patient characteristics were equally balanced between the examined groups. Adjuvant CT consisted of LV 20 mg/m(2) intravenously (i.v.) plus 5-FU 450 mg/m(2) i.v., on days 1-5 every 4 weeks for 6 cycles or 5-FU 450 mg/m(2) i.v. every week plus LVZ 50 mg t.i.d x 3 days for 1 year. All patients received radiotherapy with a three-field technique to a total dose of 45 Gy, over 5 weeks. After a median follow-up of 7.4 years there were no significant differences between the two treatment groups with respect to the recurrence rates (P=0.821). Moreover, there was no difference in disease-free survival for patients stage Dukes' B2 (log-rank p=0.73); median for LV group 90 (8-131) months, and for LVZ group 86.5 (3-129) months. No difference was noted in disease-free survival for patients stage Dukes' C (log-rank p=0.73); median for LV group 60 (17-128) months, and for LVZ group 64 (2-123) months. There was no difference in overall survival for patients stage Dukes' B2 (log-rank p=0.75); median for LV group 90 (22-131) months, and for LVZ group 86 (10-129) months. For stage Dukes' C (log-rank p=0.73); median for LV group 67 (17-128) months, and for LVZ group 64 (5-123) months. Toxicities were as follows in the 5-FU + LVZ vs 5-FU + LV group; myelosuppression (leucopenia grade 3, 12% vs 4%, p<0.04), diarrhea (grade 0, 60% vs 76%, p<0.02), and liver toxicity (increase of transaminases >3-fold, 12 patients vs 2, p<0.03), were more frequent in LVZ group. None of the patients stopped chemotherapy because of the toxicity, and there were no toxicity-related deaths. In conclusion, adjuvant chemotherapy in RC with LV + 5-FU for 6 months is equally effective and less toxic than LVZ + 5-FU for 12 months.
