Efficacy of posaconazole for treatment of basal cell carcinoma

Abstract

Background: Basal cell carcinoma (BCC) is the most commonly diagnosed skin cancer, with increasing incidence each year. Although the treatment of BCC is typically surgical, a non-surgical approach is highly desirable for patients with non-aggressive BCC recurrence, multiple tumors, poor general health, or with lesions in vulnerable areas. In the last few years, advanced cancer treatment options have targeted the Hedgehog pathway, known to regulate the proliferation of cancer stem cells and increase tumor invasiveness. Itraconazole, a triazole antifungal that inhibits ergosterol synthesis in fungi, have also proven a clinically significant tumor size reduction in BCC via inhibition of this pathway. However, serious adverse effects might preclude itraconazole use in broader population where multiple medications or comorbidities might be present. Preliminary studies demonstrate posaconazole, another member of the triazole family, may present a safer clinical alternative to the currently used pharmacological methods utilised in the management of BCC. Therefore, this phase II study aims to analyze the efficacy of posaconazole as a safe therapeutic option for nodular BCC lesions. Methods: This is a study protocol designed as a single center, randomized, double-blinded, placebo-controlled trial. Patients over 18 years of age, diagnosed with at least 2 nodular BCC lesions and that are awaiting to undergo surgery are eligible to participate in this phase II study. Before undergoing surgical excision, 170 patients (1:1 allocation) will be randomized to receive 800 mg daily of posaconazole or placebo for four weeks. Discussion: The main strengths of this study are the potential to increase general understanding of the therapeutic and metabolic impact of posaconazole. The results from this trial may also provide valuable insights to guide a larger clinical trial of posaconazole for inoperable BCC. The main limitations of the study consist of the limited intervention time frame of four weeks and the sample representativeness since it is a single-center study of patients with nodular BCC.

Skin Cancer Pathobiology at a Glance: A Focus on Imaging Techniques and Their Potential for Improved Diagnosis and Surveillance in Clinical Cohorts

“…On the basis of the aforementioned features, a prediction model was established with accuracies of 84.0% and 76.7%, respectively, in the pilot and validation cohorts, suggesting that HFUS may be a valuable tool for the differentiation of the BCCs subtypes in the clinical management of this disease [ 119 ]. In addition, HFUS may be also used to evaluate the vascularization and blood flow of BCC tumors [ 115 ] as well as in monitoring the therapeutic responses to high-dose ionizing radiation therapy [ 46 ] and Hedgehog inhibitors [ 120 ] in a non-invasive manner.…”