Photodynamic therapy (PDT) of locally recurrent breast cancer has been limited to treatment of small lesions because of non- selective necrosis of adjacent normal tissues in the treatment field. Lutetium Texaphyrin (PCI-0123, Lu-Tex) is a photosensitizer with improved tumor localization that is activated by 732 nm light, which can penetrate through larger tumors. We have evaluated Lu-Tex in a Phase I trial and in an ongoing Phase II trial in women with locally recurrent breast cancer with large tumors who have failed radiation therapy. Patients received Lu-Tex intravenously by rapid infusion 3 hours before illumination of cutaneous or subcutaneous lesions. In Phase I, Lu-Tex doses were escalated from 0.6 to 7.2 mg/kg in 7 cohorts. Sixteen patients with locally recurrent breast cancer lesions were treated. Dose limiting toxicities above 5.5 mg/kg were pain in the treatment field during therapy, and dysesthesias in light exposed areas. No necrosis of normal tissues in the treated field was noticed. Responses were observed in 60% of evaluable patients [n equals 15, 27% complete remission (CR), 33% partial remission (PR)], with 63% of lesions responding (n equals 73: 45% CR, 18% PR). In Phase II, 25 patients have been studied to date, receiving two treatments ranging from 1.0 to 3.0 mg/kg at a 21 day interval. Treatment fields up to 480 cm2 in size were treated successfully and activity has been observed. Patients have experienced pain at the treatment site but no tissue necrosis. These studies demonstrate the feasibility of Lu-Tex PDT to large chest wall areas in women who have failed radiation therapy for the treatment of locally recurrent breast cancer. Treatment conditions are currently being optimized in the ongoing Phase II trials.