OPTIMIZATION OF PHOTODYNAMIC THERAPY USING MESO-TETRA(HYDROXYPHENYL) CLORIN

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There is no cure for laryngeal papillomas. Conventional and experimental treatments can, at best, control the disease but many patients suffer frequent recurrences. We are currently testing photodynamic therapy (PDT), using dihematoporphyrin ether (DHE) (photofrin). The recurrence rate was reduced, and some patients are now free of disease. However, most patients still have recurrent disease, and not all responded. This project is a continued study of PDT efficacy, but with a new drug, meso- Tetra(hydroxyphenyl) Chlorin (mTHPC), which has potential for improved efficacy and lower photosensitivity. Patients with moderate to severe disease will be evaluated at fixed intervals for 6 months prior to PDT and 12 months post PDT, such that each patient will be used as his own control. The PDT group will also be compared to a concurrent control group with comparable disease severity receiving standard treatment. In addition to evaluating efficacy, we will ask why some patients respond while others do not. We will determine whether mTHPC levels in tissues correlate with response. We also will determine whether PDT with mTHPC induces changes in viral persistence or expression in clinically normal tissue. These studies should increase our understanding of PDT effectiveness. The specific aims address the following questions: l. Does mTHPC reduce the score reflecting recurrent growth of papilloma significantly? 2. Do age at disease onset or initiation of treatment, gender or disease severity correlate with change in score from pre- to post-treatment? 3. Do tissue and plasma levels of mTHPC at the time of treatment correlate with clinical outcome? 4. Does PDT with mTHPC eliminate persistence of HPV DNA? 5. If HPV infection remains, does PDT reduce or eliminate viral transcription and does this correlate with clinical outcome?