Phase I clinical 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 (ZnPcS 4 ), a candidate second-generation photosensitizer, in mice and evaluate the compound's safety in a phase I clinical trial of ZnPcS 4 -based 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 ZnPcS 4 . To determine safety, a rapid-titration phase I clinical trial of ZnPcS 4 -based PDT in tumor-bearing dogs was conducted. Results —In mice, administration of ≥ 100 mg of ZnPcS 4 /kg resulted in renal tubular necrosis 24 hours after IP injection. In tumor-bearing dogs, ZnPcS 4 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 ZnPcS 4 doses as low as 0.25 mg/kg. Conclusions and Clinical Relevance —A conservative starting dose of ZnPcS 4 was 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.