A 5-Year Randomized Phase III Trial of Efficacy and Safety of Photodynamic Therapy Using Porfimer Sodium in High-Grade Dysplasia in Barrett's Esophagus

摘要

Purpose: Barrett's esophagus (BE) with high-grade dysplasia (HGD) patients were enrolled in a two-year trial comparing photodynamic therapy (PDT) with porfimer sodium (POR) plus 20 mg BID omeprazole (O) [PORPDT] with standard therapy of acid suppression with O [O alone] and followed for an additional 3 years. At 2 years, HGD ablation occurred in 77% of PORPDT patients versus 39% in O alone patients (p < 0.0001). As HGD and possible cancer development in BE are inextricably linked, the trial was continued over 5 years to assess longer-term HGD ablation and cancer occurrence. Methods: Patients with BE and HGD were randomized (2:1) to PORPDT (n = 138) or O alone (n = 70). Patients on PDT received 2 mg/kg i.v. of POR followed by endoscopic laser light exposure of Barrett's mucosa at a wavelength of 630 nm within 40-50 hours up to a maximum of 3 courses administered at least 90 days apart. Every 3 months, patients underwent 4-quadrant jumbo esophageal biopsies at 2-cm intervals. Pathologists based at one center assessed biopsies and were blinded to treatment assignment and patient identity. Results: At 5 years, PORPDT was significantly more effective than O alone in eliminating HGD (p < 0.0001) and in preventing progression to cancer (p -0.027) with about twice the likelihood of cancer occurring in O alone (29%) compared to PORPDT (15%). HGD ablation at 5 years confirmed the significant difference found at 2 years (77% PORPDT, 39% O alone). Conclusions: This 5-year large randomized trial showed clearly that PORPDT is a statistically and clinically effective endoscopic therapy in eliminating HGD and in reducing the incidence of cancer in BE patients with HGD compared to O alone.