Pharmacokinetics and clinical effects of mono-L-aspartyl chlorin e6 (NPe6) photodynamic therapy in adult patients with primary or secondary cancer of the skin and mucosal surfaces

Background/Purpose: Mono-L-aspartyl chlorin e6 (NPe6) is a photosensitizer that exhibits chemical purity, absorption at 664nm wavelength and may be useful in photodynamic therapy (PDT). Methods: This open label phase I clinical trial at the University of California, Davis Medical Center examined the pharmacokinetic properties of Npe6 and clinical response to PDT with this photosensitizer. A single intravenous dose of Npe6 was administered to 14 cancer patients with superficial malignancies (basal cell carcinoma = 22 lesions, squamous cell cancer = 13 lesions, papillary carcinoma = 14 lesions). Patients received one of five ascending doses (0.5 mg/kg (n = 4), 1.0 mg/kg (n = 3), 1.65 mg/kg (n = 3), 2.5 mg/kg (n = 3), or 3.5 mg/kg (n = 1)) 4-8 h prior to light activation. The total light dose (range 25-200 J/cm²) depended on the tumor shape and size. Light was delivered using an argon-pumped tunable dye laser. Serum NPe6 concentrations were measured over a 28-day period. The toxicity and cutaneous clinical efficacy of NPe6 were observed. Results: Four weeks post-PDT, 20 of 22 basal cell carcinoma tumors (91%) showed a complete response. Eighteen of 27 other malignant cutaneous tumors showed a complete (n = 15/27, 56%) or partial (n = 3/27, 11%) response. Fewer non-responders were seen at an Npe6 dose level of 1.65 mg/kg or higher. Only 2 of 14 patients experienced an adverse event that was definitely related to NPe6 administration. Photosensitivity resolved within 1 week of NPe6 dosing in 12 of 14 patients. Analysis of serum levels of 11 individual patients indicated that a two-compartment model with a residual phase best fits the data. The mean α, β, and terminal half-lives were 8.63 ± 2.92, 105.90 ± 37.59 and 168.11 ± 53.40 h (± 1SD), respectively. The observed mean volume of distribution was 5.94 ± 2.551, and the mean clearance was 0.0394 ± 0.01321/h. These values were independent of the dose administered. Conclusion: The photosensitizer, NPe6, was well tolerated with minimal phototoxic side effects, and demonstrated preliminary efficacy against cutaneous malignancies.