A prospective randomized trial comparing intravenous 5-fluorouracil and oral doxifluridine as postoperative adjuvant treatment for advanced rectal cancer

• Published in: Annals of surgical oncology 2000-10, Vol.7 (9), p.674-679
• Main Authors: Min, J S, Kim, N K, Park, J K, Yun, S H, Noh, J K
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; Adenocarcinoma - drug therapy; Adenocarcinoma - mortality; Adenocarcinoma - pathology; Adenocarcinoma - surgery; Adjuvant therapy; Administration, Oral; Alopecia; Antimetabolites, Antineoplastic - administration & dosage; Antitumor activity; Chemoradiotherapy; Chemotherapy; Chemotherapy, Adjuvant; Colorectal cancer; Diarrhea; Disease-Free Survival; Drug Administration Schedule; Female; Floxuridine - administration & dosage; Fluorouracil - administration & dosage; Humans; Infusions, Intravenous; Intravenous administration; Leukopenia; Male; Metastases; Middle Aged; Neoplasm Recurrence, Local; Postoperative Period; Prospective Studies; Quality of Life; Rectal Neoplasms - drug therapy; Rectal Neoplasms - mortality; Rectal Neoplasms - pathology; Rectal Neoplasms - surgery; Rectum; Toxicity; Treatment Outcome
• ISSN: 1068-9265; 1534-4681
• DOI: 10.1007/s10434-000-0674-9

Postoperative adjuvant chemoradiation treatment after curative resection for rectal cancer was needed to reduce recurrence and improve a survival rate. Intravenous 5-fluorouracil (5-FU) and leucovorin has been a mainstay of chemotherapy, but oral 5-FU derivatives have been shown a comparable antitumor activity. Intravenous 5-FU and oral doxifluridine were compared with respect to therapeutic efficacy, drug toxicity, and quality of life. A total of 166 patients were randomized to receive intravenous 5-FU (450 mg/m2/day) or oral doxifluridine (900 mg/m2/day) in combination with leucovorin (20 mg/m2/day) for depth of invasion, nodal status, metastasis (TNM) stage II and III patients between October 1997 and February 1999. Consecutive daily intravenous infusion for 5 days per every month for a total of 12 cycles (IV arm, n = 74) and oral doxifluridine daily for 3 weeks and 1 week rest 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 22 daily activity items (good, > or =71; fair, < 70; poor, < 52). There was no difference of sex between two groups (IV arm: male/female = 45/29, oral arm: male/female = 59/33). The mean age was 52.3 vs. 59.5, respectively. There was also no difference of TNM stage distribution and type of operation between groups (P>.05). Mean numbers of chemotherapy cycles were 6.5+/-3.7 (IV arm) vs. 7.2+/-4.3 (oral arm), respectively. The rate of recurrence was 9/74 (12.1%) in the IV arm and 6/92 (6.5 %) in the oral arm, respectively (P = .937). Local recurrence was 2/74 (stage III; 2.7%) in the IV arm and 1/92 (stage II; 1.1%) in the oral arm, respectively. Systemic recurrence was 7/74 (stage III; 9.4%) in the IV arm and 5/92 (stage III; 5.4%) in the oral arm, respectively. The most common site of systemic recurrence was the liver. Toxicity profile was as follows: leukopenia (30/74 vs. 17/92) and alopecia (21/74 vs. 13/92) were statistically more common in the IV arm. Diarrhea was more common in the oral arm. Poor quality of life score between two groups was observed at 1 month (23.9% vs. 13%) and 2 months (15.8% vs. 3.7%) after chemotherapy. Good quality of life score was observed at 1 month (19.5% vs. 49%) and 2 months (47% vs. 72%), respectively (P