Prospective Randomized Trials Comparing Intravenous 5-Fluorouracil and Oral Doxifluridine as a Postoperative Adjuvant Treatment for Advanced Rectal Cancer

ABSTRACT

PURPOSE: Intravenous 5-Fluorouracil (5-FU) and oral doxifluridine were compared with respect to therapeutic efficacy, drug toxicity, and quality of life to clarify the efficiency of oral doxifluridine. METHODS: One hundred sixty-six (166) patients who underwent a curative resection for TNM stage II and III rectal cancer between Oct. 1997 and Feb. 1999 were randomized to receive intravenous 5-FU (450 mg/m2/day) or oral doxifluridine (700 mg/m2/day) in combination with leucovorin (20 mg/m2/day). 5-FU was infused intravenously 5 consecutive days per month for a total of 12 cycles (IV arm, N=74) in one group, and doxifluridine was given orally daily for 3 weeks with a rest of 1 week for a total of 12 cycles (Oral arm, N=92). Drug toxicity and quality of life were observed. Quality of life was scored according to twenty-two daily activity items (good,>71, fair,530.05). Mean number of chemotherapy cycles was 6.5+/-3.7 (IV arm) vs 7.2+/-4.3 (Oral arm). The recurrence rate was 9/74 (12.1%) in IV arm and 6/92 (6.5%) in oral arm (P=0.937). Local recurrence was 2/74 (stage III; 2.7%) in IV arm and 1/92 (stage II; 1.1%) in oral arm. Systemic recurrence was 7/74 (Stage III; 9.4%) in IV arm and 5/92 (Stage III; 5.4%) in oral arm. Toxicity pro-files are as follows Leukopenia (30/74, 17/92) and alopecia (21/74, 13/92) were more common in IV arm than in oral arm, and the difference was statistically significant. Diarrhea was more common in oral arm. The quality of life score was better at 1 month (19.5%, 49%) and at 2 months (47%, 72%) in the oral arm group (<0.05). CONCLUSION: Oral Doxifluridine with leucovorin as a postoperative adjuvant therapy shows a therapeutic efficacy comparable to the intravenous 5-FU regimen and has a high quality of life. The oral regimen also can be safely given with an appropriate toxicity and tolerability.