Photodynamic therapy for cancer of the upper aerodigestive tract using tetra(m-hydroxyphenyl)chlorin

A major step in the development of photodynamic therapy (PDT) is the clinical optimization and evaluation of new photosensitizers (PS). Ideally, new compounds should be more effective and/or induce fewer side effects than the first generation PS such as hematoporphyrin derivative and Photofrin. We report the results of our study of PDT applied in the human upper aerodigestive tract, using tetra(m-hydroxyphenyl)chlorin (mTHPC) as the photosensitizing drug. Twenty-seven patients with early (i.e., in situ or microinvasive) squamous cell carcinomas and 4 patients with T1 or T2 cancers were studied. In most cases, illumination of the tumor was performed 4 days after i.v. injection of 0.15 mg/kg of mTHPC using 652 or 514 nm laser light. Of the 36 early tumors evaluated 30 (83%) showed no recurrence after a mean disease-free follow-up of 15.3 months (3-35 months). Of the T1 and T2 cancers, only one achieved a complete response. Major complications, all following red light illuminations, included 1 bronchial stenosis, 1 esophagotracheal fistula, and 2 probable occult perforations of the esophagus. PDT in the esophagus with green light renders such perforations essentially impossible, without, however, reducing the efficacy of the treatment. Skin photosensitization, never observed later than the first week after injection, was seen in 12 patients. In conclusion, photodynamic therapy with mTHPC is a safe and effective technique for the treatment of early carcinomas of the upper aerodigestive tract. Its efficacy is much lower for more advanced cancers.