Silicon phthalocyanine (Pc 4) photodynamic therapy is a safe modality for cutaneous neoplasms: results of a phase 1 clinical trial

Abstract

Background: Photodynamic therapy (PDT) is a non-invasive treatment for non-melanoma skin cancer. However, PDT systems currently used clinically have limitations such as pain and superficial tissue penetration. The silicon phthalocyanine Pc 4 is a second-generation photosensitizer with peak absorption in the far red at 675 nm.

Objective: To assess the safety and tolerability of topically applied Pc 4 followed by red light (Pc 4-PDT) in treating cutaneous neoplasms.

Study design/materials and methods: Forty three adults with a diagnosis of neoplasms including actinic keratoses, Bowen's disease, squamous cell carcinoma, basal cell carcinoma, or mycosis fungoides were treated with a single administration of Pc 4-PDT and followed for 14 days. The study utilized a light and Pc 4 dose escalation design in sequential groups of three subjects each.

Results: Pc 4-PDT was well tolerated with no significant local toxicity or increased photosensitivity. It has promising biologic effects, particularly in mycosis fungoides where 14 of 35 subjects demonstrated a clinical response, which correlates with Pc 4-PDT-induced apoptosis, as measured by increased active caspase-3 in the treated skin lesions.

Conclusions: Pc 4-PDT is a safe and tolerable treatment modality that effectively triggers apoptosis in cutaneous neoplasms such as mycosis fungoides.

Fig. 1

Chemical structure of Pc 4 and excitation and emission spectra.

Fig. 2

Box plot of off-site MED at baseline and 24 hours after Pc 4-PDT. White bar = median, red box = 25th–75th percentiles, bars = entire range, whisker line = outliers.

Fig. 3

Percent area of tissue section that stained positive for active caspase 3 among responders and nonresponders to Pc 4–PDT.

Fig. 4

Left (untreated) Numerous a typical lymphocytes with halos throughout a spongiotic epidermis and prominently along the basal layer. Sparse, superficial perivascular mononuclear cell infiltrate in the dermis. Right (Pc 4–PDT treated) Basket weave ortho keratosis overlies an epidermis with rete. The papillary dermis shows fibroplasia with increased vessels and a perivascular mononuclear cell infiltrate suggesing a resolving inflammatory process.