Photodynamic therapy of non-melanoma malignant tumours of the skin using topical δ-amino levulinic acid sensitization and laser irradiation

Abstract

Eighty basal cell carcinomas (BCCs) in 21 patients, 10 lesions of Bowen's disease in three patients, and four lesions of cutaneous T-cell lymphoma in two patients, were treated with photodynamic laser therapy (PDT), using topical application of the haem precursor delta-amino levulinic acid (ALA). The diagnoses were confirmed histologically prior to treatment. Fifty-five of the BCCs were superficial lesions, and 25 were nodular. Of the 80 BCCs, 39 (49%) were located on the trunk, 36 (45%) on the head and neck region, four (15%) on the leg and one on the arm. The two principal locations of the 10 Bowen's disease lesions were the leg (50%) and the trunk (40%). The T-cell lymphoma lesions were located on the shoulder and on the arm. A water-in-oil based cream containing 20% ALA was applied to the lesions, with a margin of about 10-20 mm beyond the visible tumour border, 4-6 h before the laser procedure. During this period of time the highly fluorescent and photodynamically active substance protoporphyrin IX (Pp IX) is synthesized via the haem cycle. Laser-induced fluorescence (LIF) was used for real-time monitoring of the Pp IX distribution in the tumour and in the normal surrounding skin, before and after treatment in all patients. Before laser treatment the Pp IX distribution demonstrated by LIF showed a demarcation between tumour and normal skin of about 15:1 for BCC and Bowen's disease, and 5:1 for T-cell lymphomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Kinetics and localisation of PpIX fluorescence after topical and systemic ALA application, observed in skin and skin tumours of UVB-treated mice

“…Furthermore, the fluorescence ratio of T compared with NS between 4 and 10 h had increased from 3.3 to 4.3. This increase in fluorescence intensity and selectivity implies that treatment directly after 4-6 h ALA application, as commonly applied in human studies (Cairnduff et al, 1994;Wolf et al, 1993;Svanberg et al, 1994), may not be optimal. Instead, 4-6 h of ALA application and postponing illumination for another 4-6 h may result in improved tumour response and improved therapeutic ratio.…”

“…Topically applied ALA-PDT has proven to be a successful treatment modality for non-melanoma superficial malignant skin tumours Svanberg et al, 1994). Also, human studies have been performed using orally applied ALA (Grant et al, 1993;Regula et al, 1995) and topically applied ALA (Kriegmair et al, 1994) for endoscopic PDT treatments as well as photodetection of cancer.…”

Differentiation enhances aminolevulinic acid-dependent photodynamic treatment of LNCaP prostate cancer cells

“…Recently, a newer approach to PDT has attracted much interest, namely, the application of a pro-drug (5-aminolevulinic acid, ALA) that is converted in situ into a photosensitizing compound (protoporphyrin IX, PpIX) (Peng et al, 1997). While ALAmediated PDT has shown some promise in pilot studies of certain malignancies to date, including cancers of the skin (Svanberg et al, 1994;Fijan et al, 1995;Peng et al, 1997), the number of treatment failures remains unacceptable. While a variety of mechanisms may lead to these treatment failures, all failures by definition involve a subpopulation of cancer cells that manage to escape cell death.…”

Acceleration of ALA‐induced PpIX fluorescence development in the oral mucosa

“…Animal studies have demonstrated stronger PpIX fluorescence after application of ALA in colon [8], bladder [9], and skin tumors [10]. ALA can induce strong PpIX fluorescence in tumors of the bronchi, skin, and mammary tissue [7,[11][12][13][14]. In the oral cavity, topical ALA can be used [1,2,15].…”

“…The safety of ALA as a topical or systemic photosensitizer has been established in multiple clinical trials [7][8][9][10][11][12][13][14]. PpIX is normally present in tissues of the body.…”