Phase I clinica trial of the use of zinc phthalocyanine tetrasulfonate as a photosensitizer for photodynamic therapy in dogs

Objective - To determine the threshold for acute toxicosis of parenterally administered zinc phthalocyanine tetrasulfonate (ZnPcS₄), a candidate second-generation photosensitizer, in mice and evaluate the compounds safety in a phase I clinical trial of ZnPcS₄ photodynamic therapy (PDT) in pet dogs with naturally occurring tumors. Animals - Male Swiss-Webster mice and client-owned dogs with naturally occurring neoplasms. Procedures - For the study of acute toxicosis, mice were given graded doses of ZnPcS₄. To determine safety, a rapid-titration phase I clinical trial of ZnPcS₄-based PDT in tumor-bearing dogs was conducted. Results - In mice, administration of ≥ 100 mg of ZnPcS₄/kg resulted in renal tubular necrosis 24 hours after IP injection. In tumor-bearing dogs, ZnPcS₄ doses ≤ 4 mg/kg induced no signs of toxicosis and resulted in partial to complete tumor responses in 10 of 12 dogs 4 weeks after PDT. Tumor remission was observed with ZnPcS₄ doses as low as 0.25 mg/kg. Conclusions and clinical relevance - A conservative starting dose of ZnPcS₄ arrived at on the basis of mouse toxicosis findings. Zinc phthalocyanine tetrasulfonate-based PDT was tolerated well by all dogs and warrants further study. The identification of the maximum tolerated dose through traditional phase I clinical trials may be unnecessary for evaluating novel PDT protocols.