5-Aminolevulinic acid-mediated photodynamic therapy for oral cancers and precancers

Previous studies have used both systemic and topical 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) to treat oral precancers including oral leukoplakia (OL), oral erythroleukoplakia (OEL), and oral verrucous hyperplasia (OVH) as well as oral cancers including oral verrucous carcinoma (OVC) and oral squamous cell carcinoma (OSCC). Systemic ALA-PDT has been used to treat oral dysplastic lesions and oral cancers with promising clinical outcomes. The efficacy of a regular topical ALA-PDT (fluence rate, 100 mW/cm2; light dose, 100 J/cm2) was tested on an extensive buccal OVC and an enhanced topical ALA-PDT (fluence rate, 200 mW/cm2; light dose, 200 J/cm2) on an early-invasive OSCC; complete regression of the carcinomas was demonstrated after 28 and 18 PDT treatments, respectively. Several previous studies showed relatively good outcomes for OL lesions treated with topical ALA-PDT. However, it was found that the regular topical ALA-PDT is very effective for OVH and OEL lesions but less so for OL lesions. Better PDT outcomes are significantly associated with OVH and OEL lesions with smaller size, pink to red color, epithelial dysplasia, or thinner surface keratin layer. Moreover, the thicker surface keratin layer on the OL lesions is responsible for the relatively poorer PDT outcomes for OL lesions. In addition, both light emitting diode light- and laser light-mediated topical ALA-PDTs are comparative treatment modalities for OVH and OEL lesions. Methotrexate- or vitamin D3-preconditioned prostate or skin carcinoma cells can accumulate more intracellular protoporphyrin IX, resulting in an increased killing of these preconditioned cells by subsequent ALA-PDT. Because chemotherapy can help destroy carcinoma cells and tumor-associated vasculatures and cryotherapy pretreatment may help the diffusion of ALA into lesional epithelial cells, the chemotherapy or cryotherapy-combined topical ALA-PDT may be a new effective PDT alternative for treatment of oral precancers and cancers. It is concluded that topical ALA-PDT using either light emitting diode or laser light is very effective for OVH and OEL lesions but is relatively less effective for OL lesions. If OVC or early-invasive OSCC has no concurrent regional or distant metastasis, regular or enhanced topical ALA-PDT may have a high potential to treat these two particular kinds of oral cancer. A large-scale human clinical trial is needed to evaluate the efficacies of drug-preconditioned topical ALA-PDT and chemotherapy or cryotherapy-combined topical ALA-PDT on oral precancers, OVC and early-invasive OSCC in the near future.