Oral therapy for nonmelanoma skin cancer in patients with advanced disease and large tumor burden: a review of the literature with focus on a new generation of targeted therapies

Abstract

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.

Neoplastic Multifocal Skin Lesions: Biology, Etiology, and Targeted Therapies for Nonmelanoma Skin Cancers

“…Oral therapy in NMSC is helpful in high-risk patients with recurrent and aggressive illness, who may not tolerate other systemic therapies [5]. Oral therapies which have shown at least partial efficacy include retinoids (isotretinoin, etretinate, acitretin, retinoic acid in combination with interferon-α, and cisplatin), 5-fluorouracil (5-FU), capecitabine, nonsteroidal anti-inflammatory drugs (NSAIDs), difluoromethylornithine, epigallocatechin gallate, sylimarin, curcumin, and lycopene.…”

“…However, further studies are needed in order to discriminate the differences in tumor response between locally invasive and metastatic BCCs. This concern is extremely important if other hedgehog inhibitors show increased efficacy in metastatic disease or if other different pathways could be explored for metastatic disease targeting [5]. …”

“…It has demonstrated comparative results to vismodegib for locally advanced BCC [64]. It is suggested that commercial sonidegib capsules should be formulated by wet granulation in order to increase its absorption [5]. …”

“…BCCs and SCCs constitute the vast majority and occur in a ratio of 4:1 [4]. Other pathologies represent a relatively small proportion of diagnoses compared to BCCs and SCCs [5]. BCCs do not proliferate rapidly and most of the times do not metastasize, but, if ignored, they are prone to destroy local underlying tissues [6].…”

Anti-Proliferative Effects of Piroxicam and Nimesulide on A431 Human Squamous Carcinoma Cell Line

“…Treatments used for SCC include surgical excision, topical and systemic chemotherapy (4). Some chemotherapeutic agents have been used to treat SCC such as cisplatin, doxorubicin, 5-fluorouracil, vincristine and bleomycin.…”