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Lutetium texaphyrin (PCI-0123) is currently in clinical trials as a PDT agent for the treatment of cancer patients. The drug is cleared rapidly from the plasma, and photoirradiation can be performed shortly after drug administration.T He photosensitizer as yet does not appear to elicit any significant skin photosensitivity. These characteristics favor frequent multiple PDT treatments with PCI-0123. In order to support repeated PDT treatments in the clinic, the safety of multiple drug dosing was studied in rats and mice. In rats, each group received 5 consecutive daily intravenous administrations of 5, 15, 30, or 60 mg/kg/day of PCI-0123. There were no deaths in any of the groups, and no drug-related effects were detected in the 5 mg/kg/day group. In mice, there were no observable signs of toxicity after consecutive daily administration of 10 micrometers ol/kg/day of PCI-0123 for 13 days. The feasibility and efficacy of repeated PDT treatments were assessed in C3H mice bearing RIF-1 tumors. Repeated PDT proved to be superior to a single PDT treatment. Repeated PDT treatments were well tolerated. Seven PDT treatments were administered over a nine day period without significant toxicity while achieving good therapeutic responses. All six groups receiving repeated PDT treatments showed an improved response compared to groups receiving a single PDT cycle, and the improvement was statistically significant for five of these groups. Sixty-two percent of mice receiving four sequential daily treatments were cured, and daily treatments were superior to regimens with longer intervals between PDT cycles.
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