Repeated Complete Response With Intermittent Oral S‐1 Monotherapy for Cutaneous Apocrine Carcinoma: A Case Report

Cutaneous apocrine carcinoma (CAC) is a rare form of cutaneous adenocarcinoma. Achieving a complete response (CR) in cases with metastatic CAC remains uncommon. Here, we report a case of advanced CAC, in which intermittent S-1 (a well-tolerated oral antitumor agent [1]) monotherapy was effective over a prolonged period, achieving repeated CR. A 77-year-old woman presented with a slowly growing plaque over the sternoclavicular joint region, which had initially developed two years before. Physical examination revealed a reddish, firm plaque (Figure 1a). Skin biopsy revealed diffuse infiltration of atypical tumor cells with abundant eosinophilic cytoplasm in the dermis (Figure 1b). The tumor cells were positive for CK7 and GCDFP-15 (Figure 1c), but negative for human epidermal growth factor receptor 2 (HER2), estrogen receptor, and progesterone receptor. Based on these findings, the lesion was diagnosed as CAC. Computed tomography (CT) revealed multiple enlarged lymph nodes (LNs) in the cervical regions, suggesting metastases (Figure 2a). Combination therapy with epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) was initiated; however, radiotherapy was declined by the patient. After two cycles of the combination therapy, both the plaque and lymphadenopathy regressed (Figure 2b). However, the patient developed grade 4 neutropenia and grade 2 nausea. Considering her preference for oral therapy, oral S-1 (100 mg/body/day) was initiated after discontinuation of the combination therapy. S-1 was administered for 2 weeks, followed by a one-week rest interval. Two months after S-1 initiation, both lesions had completely regressed, indicating a CR (Figure 2c). S-1 was continued for 6 months after achieving CR but was then discontinued at the patient's request. However, 1 year after cessation, erythema at the primary site and lymphadenopathy reappeared, indicating locoregional recurrence (Figure 2d). S-1 was restarted, and CR was achieved 2 months later (Figure 2e). This cycle of S-1 administration until CR, followed by cessation and subsequent recurrence, was repeated multiple times. During S-1 monotherapy, the patient developed grade 2 hand-foot syndrome, which was effectively managed with topical steroid ointments. S-1 remained effective for over 8 years after the initial administration, achieving a total of six CRs following episodes of locoregional recurrence. However, S-1 eventually lost efficacy, with enlargement of the primary lesion and cervical LNs. The patient declined further treatment. While HER2 inhibitors may be effective for HER2-positive CAC, a range of conventional chemotherapies can be considered for HER2-negative disease [2]. Nevertheless, CR to chemotherapy in CAC has been reported only rarely [2]. A remarkable response to combined paclitaxel and carboplatin has been reported in one case [3]. Additionally, CR was reported in two CAC cases: one with oral S-1 monotherapy and the other with epirubicin plus cyclophosphamide (EC) followed by S-1 monotherapy [4, 5]. In the present case, EC was discontinued due to adverse events despite a partial response. As the patient subsequently preferred oral therapy, S-1 monotherapy was administered, and CR was successfully achieved. Therefore, both EC and S-1 monotherapy may constitute feasible treatment options for CAC. In the present case, S-1 was administered intermittently until CR was achieved, followed by treatment cessation. As a result, S-1 remained effective for over 8 years following initial administration, achieving CR six times over that period. This indicates the potent and long-term antitumor effect of S-1. Despite the prolonged treatment course, the only observed adverse event was grade 2 hand-foot syndrome. In contrast, during EC therapy, the patient developed grade 4 neutropenia, posing a significant risk of fatal infection, particularly in older adults. Given its favorable safety profile and potent antitumor effect, we propose that S-1 monotherapy should be actively considered as a treatment option for metastatic CAC, particularly for older adult patients, as demonstrated in this case. We thank Thomas D. Mayer (Medical English Communications Center, Faculty of Medicine, University of Tsukuba) for useful comments. The authors have nothing to report. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.