lde225 and Carcinoma--Squamous-Cell

Although surgical intervention remains the standard of care for nonmelanoma skin cancer, other treatment modalities have been studied and used. Nonsurgical treatment methods include cryotherapy, topical medications, photodynamic therapy, radiation therapy, Hedgehog pathway inhibitors, programmed cell death protein 1 inhibitors, and active nonintervention. Despite the favorable efficacy of surgical treatment methods, many factors, including but not limited to patient age, preference, and severity of disease, must be taken into consideration when choosing the most appropriate, patient-centered treatment approach.

Topics: Administration, Cutaneous; Anilides; Antineoplastic Agents; Antineoplastic Agents, Immunological; Biphenyl Compounds; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cryosurgery; Cyclooxygenase Inhibitors; Diclofenac; Diterpenes; Fluorouracil; Humans; Imiquimod; Photochemotherapy; Programmed Cell Death 1 Receptor; Pyridines; Radiotherapy; Skin Neoplasms; Watchful Waiting

Locally advanced and metastatic nonmelanoma skin cancer (NMSC) not amenable to surgical resection requires a different approach to therapy.. To review the efficacy and adverse effects of emerging treatment options for locally advanced and metastatic NMSC.. A comprehensive search on PubMed was conducted to identify relevant literature investigating the role of program cell death 1 (PD-1) inhibitor, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor, epidermal growth factor receptor (EGFR) inhibitor, and Hedgehog pathway inhibitors in the treatment of NMSC.. PD-1 inhibitor and CTLA-4 inhibitor have shown promising efficacy with tolerable side-effect profiles in the treatment of NMSC, although the number of cases reported is limited. Currently, 3 larger-scale clinical trials are investigating PD-1 inhibitor therapy for NMSC. Similarly, EGFR inhibitor demonstrated marginal success in unresectable cutaneous squamous cell carcinomas. Hedgehog pathway inhibitors were approved by the US FDA for treatment of locally advanced and metastatic basal cell carcinomas and have shown favorable efficacy. Common adverse effects included muscle spasm, alopecia, and dysgeusia.. Systemic therapies including PD-1 inhibitors and CTLA-4 inhibitors have demonstrated early promising results for difficult-to-treat NMSC. Future studies are necessary to optimize treatment outcome.

Topics: Anilides; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Biphenyl Compounds; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cetuximab; CTLA-4 Antigen; ErbB Receptors; Hedgehog Proteins; Humans; Ipilimumab; Nivolumab; Programmed Cell Death 1 Receptor; Pyridines; Skin Neoplasms

Nonmelanoma skin cancer (NMSC) is the most common cancer in patients and includes basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Treatments useful for SCC and BCC include surgical, topical, and in advanced cases systemic chemo-radiation. This review of the literature aims to describe previous and current treatment options for oral therapy in locally advanced and metastatic NMSC otherwise unamenable to standard treatment. Oral Smoothened (Smo) inhibitors Vismodegib, Sonidegib, and Taladegib have shown to be effective in several trials. Oral tyrosine kinase inhibitors Erlotinib and Gefitinib, which target epidermal growth factor receptor (EGFR), have early supporting data and are currently undergoing large multicenter trials. Other less studied oral therapies which have shown at least partial efficacy include 5-Fluorouracil, capecitabine, and picropodophyllin. In vitro studies have elucidated new targets for dual combination oral therapy targeting both EGFR and insulin-like growth factor 1 receptor (IGF-1R). It is important to stratify treatment options based on patient risk of advanced disease, failure of conservative treatment, and ill-tolerated intravenous chemotherapy adverse events. Oral therapy in NMSC is useful in high risk patients with recurrent and aggressive disease who may not tolerate other systemic therapies.

Topics: Administration, Oral; Anilides; Antineoplastic Agents; Biphenyl Compounds; Capecitabine; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; ErbB Receptors; Erlotinib Hydrochloride; Fluorouracil; Gefitinib; Hedgehog Proteins; Molecular Targeted Therapy; Phthalazines; Podophyllotoxin; Pyridines; Quinazolines; Receptor, IGF Type 1; Retinoids; Skin Neoplasms; Tumor Burden

A 78-year-old woman was referred to our skin cancer centre with three previous incomplete resections in the left cavum conchae of a deep-infiltrating locally advanced, but still asymptomatic basal cell carcinoma (BCC). The patient noted furthermore two rapidly growing exophytic lesions in the left preauricular and cervical area in the last weeks. The clinical and histological distinction of locally advanced from metastatic cutaneous squamous cell carcinoma (CSCC) lesions was challenging. Imaging analysis with CT scans showed, however, an involvement of the parotid gland as well as multiple small lymph node metastases. The interdisciplinary tumour board decision at our institution recommended a systemic treatment with the PD1-antibody cemiplimab. After 13 cycles with cemiplimab at a dose of 350 mg intravenously every 3-weeks, the patient showed a complete response of the two CSCC lesions with histological confirmation. However, the BCC of the left ear appeared to be unchanged and still asymptomatic. The interdisciplinary tumour board considered this tumour to be no candidate for a curative resection or irradiation. Therefore, the patient was exposed to the hedgehog inhibitor sonidegib with a conventional dose of 200 mg orally per day. After 3 months of treatment, the tumour showed a markable regression and a complete response was confirmed by 3-punch biopsies from this preoperated lesion. Both cemiplimab and sonidegib were excellently tolerated with almost no adverse events apart from a mild fatigue (CTC grade 1) over the first 3 weeks of the cemiplimab therapy. There were no laboratory abnormalities found.

Topics: Aged; Antibodies, Monoclonal, Humanized; Biphenyl Compounds; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Epithelial Cells; Female; Hedgehog Proteins; Humans; Pyridines; Skin Neoplasms

Topics: Anilides; Antineoplastic Agents; Antineoplastic Agents, Immunological; Biphenyl Compounds; Carcinoma, Squamous Cell; Clinical Trials as Topic; Drugs, Investigational; Humans; Molecular Targeted Therapy; Pyridines; Skin Neoplasms