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


METHODS
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).


RESULTS
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<.05).


CONCLUSIONS
Oral doxifluridine with leucovorin shows a comparable therapeutic efficacy to intravenous 5-FU regimen with high quality of life as postoperative adjuvant therapy. The oral regimen also can be safely given with appropriate toxicity and tolerability.
Min
J S
JS
Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.
Kim
N K
NK
Park
J K
JK
Yun
S H
SH
Noh
J K
JK
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000284:Administration, Oral; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage*; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011184:Postoperative Period; D011446:Prospective Studies; D011788:Quality of Life; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D005467:Floxuridine; D005472:Fluorouracil; C025034:doxifluridine