Photodynamic therapy with porfimer sodium for ablation of high-grade dysplasia in Barrett's esophagus: international, partially blinded, randomized phase III trial.
BACKGROUND
Barrett's esophagus (BE) may lead to high-grade dysplasia (HGD) and adenocarcinoma. The objective was to examine the impact of treating patients with BE and with HGD by using porfimer sodium (POR) and photodynamic therapy (PDT) for ablating HGD and reducing the incidence of esophageal adenocarcinoma.


METHODS
The design was a multicenter, partially blinded (pathology), randomized clinical trial conducted in patients with BE who have HGD. There were 30 contributing centers. A total of 485 patients were screened, with 208 in the intent-to-treat population and 202 in the safety population. Patients were randomized on a 2:1 basis to compare PDT with POR plus omeprazole (PORPDT) with omeprazole only (OM). The main outcome measurement was complete HGD ablation occurring at any time during the study period.


RESULTS
There was a significant difference (p < 0.0001) in favor of PORPDT (106/138 [77%]) compared with OM (27/70 [39%]) in complete ablation of HGD at any time during the study period. The occurrence of adenocarcinoma in the PORPDT group (13%) (n=18) was significantly lower (p < 0.006) compared with the OM group (28%) [corrected] (n=20). The safety profile showed 94% of patients in the PORPDT group and 13% of patients in the OM group had treatment-related adverse effects. The limitations of the study were that PDT therapy may have had to be applied more than once and that patients spent more time in treatment. The patients and the physicians were not blinded to the treatment.


CONCLUSIONS
PORPDT in conjunction with omeprazole is an effective therapy for ablating HGD in patients with BE and in reducing the incidence of esophageal adenocarcinoma.
Overholt
Bergein F
BF
Thompson Cancer Survival Center, Knoxville, Tennessee, USA.
Lightdale
Charles J
CJ
Wang
Kenneth K
KK
Canto
Marcia I
MI
Burdick
Steven
S
Haggitt
Roger C
RC
Bronner
Mary P
MP
Taylor
Shari L
SL
Grace
Michael G A
MG
Depot
Michelle
M
D000230:Adenocarcinoma / Q000473:pathology / Q000517:prevention & control; D000368:Aged; D001471:Barrett Esophagus / Q000188:drug therapy* / Q000473:pathology; D001706:Biopsy; D017323:Dihematoporphyrin Ether / Q000627:therapeutic use*; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000473:pathology / Q000517:prevention & control; D004945:Esophagoscopy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007391:International Cooperation; D008297:Male; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011230:Precancerous Conditions / Q000188:drug therapy* / Q000473:pathology; D011446:Prospective Studies; D016896:Treatment Outcome
D017319:Photosensitizing Agents; D017323:Dihematoporphyrin Ether