Phase I/II Clinical Study of Next-Generation Photodynamic Therapy (L-PDT) Using Talaporfin Sodium (Laserphyrin®) for Cervical Intraepithelial Neoplasia: Efficacy, Safety, and Fertility Preservation.

BACKGROUND PDT using Photofrin® (P-PDT) has been applied to over 900 gynecologic tumor cases since 1989, demonstrating excellent efficacy and fertility preservation; however, post-treatment photosensitivity has limited its clinical application for CIN and cervical cancer. This study aimed to establish a safe, effective, and fertility-preserving alternative to cervical conization.

METHODS To overcome photosensitivity, we conducted a prospective Phase I/II clinical study to evaluate the safety, efficacy, oncological control, and fertility outcomes of L-PDT using talaporfin sodium (Laserphyrin®) and a diode laser for CIN grades 2-3. Forty-three women with biopsy-confirmed CIN2-3 were enrolled. Phase I determined the optimal light dose (50, 75, or 100 J/cm²), and Phase II assessed efficacy and safety at 100 J/cm². Talaporfin sodium (40 mg/m²) was administered intravenously 4 hours before laser irradiation under colposcopic guidance.

RESULTS Complete response (CR) was achieved in 95% (95% CI: 89.1-100%) at 3 months and 98% (95% CI: 93.2-100%) at 6 months after treatment. Original high-risk human papillomavirus clearance was 92.5% at 3 months and 95% at 12 months. Adverse events were mild and transient, including abdominal pain and low-grade fever. No recurrences occurred during a median follow-up of 66.4 months among patients achieving CR. Among women desiring pregnancy, the conception rate was 74% (23/31) and the live birth rate was 79% (27/34), with a low preterm birth rate of 3.7% (1/27).

CONCLUSIONS These results suggest that L-PDT is a safe and highly effective non-excisional treatment for CIN that may contribute to fertility preservation; however, potential advantages over conventional conization and laser vaporization need to be confirmed in comparative studies.