Effects of long-term rofecoxib on gastric intestinal metaplasia: results of a randomized controlled trial.
OBJECTIVE
Gastric cancer and its premalignant gastric lesion, intestinal metaplasia (IM), frequently express cyclooxygenase-2 (COX-2) at high levels. We tested whether long-term use of specific COX-2 inhibitors regress gastric IM.


METHODS
This is a double-blind, randomized, placebo-controlled trial. Individuals with confirmed IM and Helicobacter pylori clearance were randomized to receive rofecoxib 25 mg daily or placebo. Endoscopy was done at baseline, at the end of year 1, and at the end of year 2, with multiple biopsies taken from the antrum and corpus. The primary end point was the proportion of subjects with regression of IM. Secondary end points were the severity of other histologic variables and the proportion of subjects with complete regression of IM.


RESULTS
Two-hundred and thirteen subjects with confirmed IM were randomized. The proportion of subjects with the regression of IM did not differ significantly between rofecoxib and placebo groups (antrum, 24.5% versus 26.9%; P = 0.74; corpus, 4.3% versus 2.2%; P = 0.68). Patients on rofecoxib (19.1%) and on placebo (16.1%) had no IM detected in the stomach (P = 0.59). There was also no significant difference in the severity of IM between the two treatment groups (P >or= 0.3).


CONCLUSIONS
There was no trend to suggest that treatment with rofecoxib for 2 years resulted in the regression of gastric IM. Although our findings cast doubt on the reversibility of gastric IM by COX-2 inhibitor, further studies are needed to establish the role of COX-2 inhibitors in different stages of gastric carcinogenesis.
Leung
Wai K
WK
Institute of Digestive Disease, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong. wkleung@cuhk.edu.hk
Ng
Enders K W
EK
Chan
Francis K L
FK
Chan
Wing Y
WY
Chan
Kui-fat
KF
Auyeung
Alex C M
AC
Lam
Candice C H
CC
Lau
James Y W
JY
Sung
Joseph J Y
JJ
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000970:Antineoplastic Agents / Q000008:administration & dosage; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005500:Follow-Up Studies; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007783:Lactones / Q000008:administration & dosage*; D008297:Male; D008679:Metaplasia / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D010919:Placebos; D011446:Prospective Studies; D013450:Sulfones / Q000008:administration & dosage*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D007783:Lactones; D010919:Placebos; D013450:Sulfones; C116926:rofecoxib