Photodynamic therapy with 3-(10-hexyloxyethyl) pyropheophorbide a for cancer of the oral cavity

Purpose: The primary objective was to evaluate safety of 3-(1'-hexyloxyethyl) pyropheophorbide-a (HPPH) photodynamic therapy (HPPH-PDT) for dysplasia and early squamous cell carcinoma of the head and neck (HNSCC). Secondary objectives were the assessment of treatment response and reporters for an effective PDT reaction. Experimental Design: Patients with histologically proven oral dysplasia, carcinoma insitu, or early-stage HNSCC were enrolled intwo sequentially conducted dose escalation studies with anexpanded cohortat the highest dose level. These studies used an HPPH dose of 4 mg/m² and light doses from 50 to 140 J/cm². Pathologic tumor responses were assessed at 3 months. Clinical follow up range was 5 to 40 months. PDT induced cross-linking of STAT3 were assessed as potential indicators of PDT effective reaction. Results: Forty patients received HPPH-PDT. Common adverse events were pain and treatment site edema. Biopsy proven complete response rates were 46% for dysplasia and carcinoma in situ and 82% for squamous cell carcinomas (SCC) lesions at 140 J/cm2. The responses in the carcinoma in situ/dysplasia cohort are not durable. The PDT-induced STAT3 cross-links is significantly higher (P =0.0033) in SCC than in carcinoma in situ/dysplasia for all light doses. Conclusion: HPPH-PDT is safe for the treatment of carcinoma in situ/dysplasia and early-stage cancer of the oral cavity. Early-stage oral HNSCC seems to respond better to HPPH-PDT in comparison with premalignant lesions. The degree of STAT3 cross-linking is a significant reporter to evaluate HPPH-PDT-mediated photoreaction.