• dermatology
• dermatological tumors
• oncology
• chemotherapy
• adverse effects

Advanced cutaneous squamous cell carcinoma (cSCC) with nodal and/or distal metastases or large local spreading is inoperable, and treatment options for patients are usually limited to chemotherapy and radiation. The National Comprehensive Cancer Network (NCCN) Guidelines include some regimens of cisplatin- (CDDP) based systemic therapies, but no chemotherapy has yet been established for advanced cSCC.1 Peplomycin sulfate, bleomycin, and irinotecan are licensed for cSCC in Japan but are not commonly used in actual clinical practice because of their low efficacy and severe side effects (such as interstitial pneumonia, myelosuppression, and adverse digestive symptoms). CA regimen, the combination of CDDP and adriamycin (ADM), has been reported to show a response rate of about 60% for advanced cSCC,2 whereas other regimens, such as CDDP plus 5-fluorouracil or CDDP plus cetuximab, have shown a response rate of less than 20%.3 Suzuki et al 4 and Nakamura et al 5 previously reported a C’A’ regimen, modified from the CA regimen, using carboplatin (CBDCA) and epirubicin (EPI). This regimen is preferable for older people and patients with underlying disorders, because it reduces the nephrotoxicity of CDDP and the cardiac toxicity of ADM.4 Nevertheless, as the number of reported cases treated with this regimen remains scant, further validation is required. Here, we report three cases of advanced cSCC treated with a combination of CBDCA and EPI.

Clinical profiles of the patients are summarised in table 1. The patients had past histories of burn scar, lichen sclerosus et atrophicus, and external injury, respectively. Case three was complicated with mild kidney failure. In all cases, primary cSCC lesions were surgically resected, aiming for local control. The patients then received chemotherapies with an area under the curve (AUC) 5 dose of CBDCA and 60 mg/m² of EPI, because of the high-risk characteristics of the primary lesions mentioned in the NCCN Guidelines (such as potential nodal metastases or distal metastases). As the tumour of case two transformed into a granulocyte colony-stimulating factor- (G-CSF) producing tumour and rapidly progressed shortly after the initial course of the chemotherapy, it was impossible for the patient to receive a second treatment course. The patients in the other two cases received four courses of the regimen, and their progression-free survival periods were 4 and 6 months, respectively. Neutropenia (over grade 3) was observed in every treatment course and in all cases.

Although the risk of nodal metastases and distal metastases in cSCC is relatively low, currently licensed cSCC chemotherapies and radiation therapy are unsatisfactory in terms of both efficacy and safety. Two out of the three patients treated with C’A’ regimen considered in this report achieved a progression-free period of several months, without serious adverse events (except for haematological toxicity). Notably, all three cases avoided death from the C’A’ regimen, in spite of their poor Eastern Cooperative Oncology Group (ECOG)-Performance Status (PS) (from Score 2 to 3), suggesting a good tolerability of this regimen. Further documentation of cases of cSCC treated with C’A’ regimen is warranted to establish this regimen as an option for the treatment of advanced cSCC.