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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
Author(s) -
Chan Andrew L.,
Juarez Maya,
Allen Roblee,
Volz William,
Albertson Timothy
Publication year - 2005
Publication title -
photodermatology, photoimmunology and photomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.736
H-Index - 60
eISSN - 1600-0781
pISSN - 0905-4383
DOI - 10.1111/j.1600-0781.2005.00138.x
Subject(s) - photodynamic therapy , medicine , photosensitizer , pharmacokinetics , photosensitivity , basal cell carcinoma , adverse effect , gastroenterology , toxicity , cancer , carcinoma , skin cancer , nuclear medicine , urology , basal cell , chemistry , physics , organic chemistry , quantum mechanics
Background/Purpose: Mono‐ l ‐aspartyl chlorin e6 (NPe6) is a photosensitizer that exhibits chemical purity, absorption at 664 nm 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/cm 2 ) 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 (±1 SD), respectively. The observed mean volume of distribution was 5.94±2.55 l, and the mean clearance was 0.0394±0.0132 l/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.