talaporfin and Skin-Neoplasms

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).. 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.. 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 alpha, beta, 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.. The photosensitizer, NPe6, was well tolerated with minimal phototoxic side effects, and demonstrated preliminary efficacy against cutaneous malignancies.

Topics: Aged; Aged, 80 and over; Carcinoma, Basal Cell; Carcinoma, Papillary; Carcinoma, Squamous Cell; Female; Humans; Male; Middle Aged; Photochemotherapy; Photosensitizing Agents; Porphyrins; Skin Neoplasms; Treatment Outcome

We observed real-time spectral images using line-scan imaging spectrography in order to evaluate tumor viability.. Japanese albino rabbits, which underwent the implantation of VX2 tumor strain, were used as subcutaneous tumor models (n = 54). Photodynamic therapy (PDT) consisted of semiconductor laser irradiation of the tumorous lesion. The experimental groups consisted of a PDT group (n = 15) and a non-PDT group (control group, n = 15). The spectral images taken by a CCD camera underwent computer processing. Next, the spectrum of the tumorous lesion was observed and the peak spectrum value was measured.. Two peaks (545 and 575 nm) corresponding to the absorbance spectrum of oxygenated hemoglobin (oxyHgb) were observed in the untreated area. In the treated area, however, they disappeared and a different peak (560 nm) corresponding to the absorbance spectrum of deoxygenated hemoglobin was observed. PDT induced ischemic tissues and the cells could be confirmed in real time in vivo in monochrome and color images reflecting the oxyHgb amount. A histopathological examination and phosphotungstic acid hematoxylin staining demonstrated diffuse fibrin accumulation in the microvessels, while proliferating cell nuclear antigen staining showed a reduced nuclear stainability.. These results demonstrated that the real-time spectral images showed the actual histological conditions such as a blocked tumor blood flow and reduced tumor viability.

Topics: Animals; Carcinoma, Squamous Cell; Disease Progression; Male; Neoplasms, Experimental; Photochemotherapy; Photosensitizing Agents; Porphyrins; Rabbits; Skin Neoplasms; Spectrophotometry; Treatment Outcome