Photodynamic therapy using mono-L-aspartyl chlorin e6 (Npe6) for the treatment of cutaneous disease: a Phase I clinical study.

The activity of a new photosensitizer, mono-L-aspartyl chlorin e6 (Npe6), was assessed in an ascending dose Phase I study for patients with superficial tumor. Eleven patients, with a total of 14 tumor sites, were treated with photodynamic therapy (PDT) using Npe6. Lesions included recurrent adenocarcinoma of the breast, basal cell carcinoma, and squamous cell carcinoma. The phototherapy protocol consisted of a single i.v. injection of 0.5-3.5 mg/kg Npe6, followed 4 h later by 25-100 j/cm2 at 664 nm of light. PDT using Npe6 caused no significant toxicity with the exception of temporary generalized skin photosensitivity. In all cases, light treatment caused immediate tissue blanching, followed by a marked necrosis of the tumor mass. Regression of tumor occurred over 24-48 h after the light treatment and was followed by the formation of a heavy eschar over the tumor site. Tumor regression was short-lived at Npe6 doses of 1.65 mg/kg and below. In two of three patients, tumor regression was either incomplete or tumors recurred within the 12-week observation period. Increasing the Npe6 dose to 2.5 or 3.5 mg/kg combined with 100 J/cm2 of light energy resulted in better control of tumor regrowth with 66% (6/9) of sites remaining tumor-free through 12 weeks observation. This increased tumor response came at the expense of the tissue selectivity observed at Npe6 doses of 1.65 mg/kg and below. There was no apparent selectivity for destruction of tumor compared with normal skin at Npe6 doses of 2.5 mg/kg and above. These data demonstrate that Npe6 is both an effective and safe photosensitizer for use in PDT and provide the impetus for continued study in Phase II clinical trials.