Therapy of Advanced Squamous Cell Carcinoma of the Skin

Abstract

Advanced unresectable squamous cell carcinoma of the skin (SCCS) is a rare condition, which is difficult to treat. Because of its rarity, few therapeutic trials are available. Moreover, SCCS often occur in elderly. Conventional treatment options for advanced SCCS are chemotherapy mainly with cisplatin-based regimens. Immunotherapy with interferon alpha and retinoids combination was also shown to be efficient. Toxicity of these treatments limits, however, their use in elderly patients and an initial work up for a global assessment is needed in order to adapt the choice. More recently, epithelial growth factor receptor (EGFR) targeted therapies have been developed and induced interesting response rates in small series of patients with unresectable SCCS. Their efficacy in SCCS must be confirmed by larger phase III trials and the identification of predictive biological factors of response is warranted. New therapeutic approaches combining EGFR inhibitors either with IGFR inhibitors, or immunomodulators or inhibitors of the PI3K/AKT/mTOR pathway are currently under evaluation in head and neck carcinomas and might represent valuable therapeutic approaches for unresectable SCCS. Moreover, there are several new molecular candidate treatment targets for unresectable SCCS including somatic NOTCH1 or NOTCH2 inactivating mutations, ALK1, which could be a good candidate for antiangiogenic therapy and matrix metallopeptidase 7, which enhances proliferation, migration, and invasion of cancer cells. Organ transplant recipients often develop SCCS and in some patients, SCCS are rapidly progressing. Management of SCCS in this subgroup of patients includes both carcinologic treatment and modification of immunosuppression. Specific treatment is generally the same as in immunocompetent patients. Switching from calcineurin inhibitors to sirolimus or reducing immunosuppression has to be considered.

Pharmacologic treatment options for advanced epithelial skin cancer

“…Similar to BCCs, aSCCs are defined as tumours that are unresectable due to their location around critical structures, that is, ear, nose, orbital area, due to deep invasion of underlying structures such as bone, nerve or muscle or due to metastasis in regional lymph nodes or other distant areas [60]. Staging criteria of SCCs are summarized in Table 2.…”

“…Cisplatin has been used in a number of combinations with mixed results. These include combinations with bleomycin, doxorubicin, 5-FU and bleomycin, and a combination of chemoradiation with 5-FU [60]. Guthrie et al reported encouraging results in two different studies, where a combination of cisplatin and doxorubicin was used [61,62].…”

“…These results might not be applicable to cSCC, but may demonstrate the importance of finding alternate routes or schedules of administration for conventional therapies [64]. Other studies where bleomycin and 5-FU were used as monotherapy yielded disappointing results [60]. Doclitaxel and paclitaxel have also been used alone or in combination with other medications in the treatment of aSCC with mixed results [60].…”

“…Other studies where bleomycin and 5-FU were used as monotherapy yielded disappointing results [60]. Doclitaxel and paclitaxel have also been used alone or in combination with other medications in the treatment of aSCC with mixed results [60].…”

“…These medications fall under two main categories: monoclonal antibodies that competitively inhibit EGFR and other, smaller, molecules that selectively inhibit the tyrosine kinase domain of EGFR. None of these therapies is currently approved for the treatment of cutaneous aSCC, however, data from Phase I and II trials show promising results [60].…”