Electrochemotherapy in advanced skin tumors and cutaneous metastases - a retrospective multicenter analysis.

BACKGROUND AND OBJECTIVES: Once classic treatments such as chemotherapy or radiation therapy have been exhausted, only few therapeutic options remain for extensive skin tumors or cutaneous metastases. In such cases, electrochemotherapy may be considered as alternative therapy. PATIENTS AND METHODS: In this retrospective study, clinical features, treatment response, and adverse effects were evaluated in 56 patients treated with electrochemotherapy at six German dermatology departments. RESULTS: The mean age of the patient cohort (14 men, 42 women) was 69.3 years. Included were 20 patients with skin metastasis of advanced malignant melanoma, 13 patients with breast cancer metastases, 15 patients with primary squamous cell carcinoma of the skin or cutaneous metastases of other carcinoma types, and 8 patients with cutaneous lymphoma or sarcoma. The overall response rate was 44.6% (10.7% complete response; 33.9% partial response). By contrast, 31 (55.4%) patients did not respond (12.5% had stable disease; 42.9%, tumor progression). Patients with melanoma and cutaneous lymphoma or sarcoma responded significantly better than those with carcinoma. Roughly one quarter of patients showed an improvement in tumor-related exudation, fetor, and chronic bleeding. CONCLUSION: Showing only few adverse effects, electrochemotherapy was effective in about one half of the patients with advanced tumors. Treatment response appears to depend on the tumor entity.

Evaluation of real-world treatment outcomes in patients with distant metastatic Merkel cell carcinoma following second-line chemotherapy in Europe.

BACKGROUND AND AIMS: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer; few treatments exist for patients with advanced disease. Once tumors metastasize to distant sites, patients generally receive chemotherapy, but response duration and progression-free survival (PFS) are typically short. Few studies have assessed the efficacy of second-line chemotherapy for metastatic MCC. Here, we studied outcomes in patients who received ≥ 2 lines of chemotherapy for metastatic MCC. MATERIALS AND METHODS: Patients in an MCC-specific registry diagnosed with stage IV MCC between November 1, 2004, and September 15, 2015, and treated with second-line or later chemotherapy were analyzed retrospectively. Patient records, including baseline characteristics, immunocompetent status, and responses to prior chemotherapy, were evaluated. Patients meeting eligibility criteria were followed through December 31, 2015. RESULTS: Of 29 patients with metastatic MCC and immunocompetent status who had received ≥ 2 lines of chemotherapy, 3 achieved a partial response, for an objective response rate (ORR) of 10.3% (95% CI, 2.2-27.4). In the overall population including patients with immunocompetent and immunocompromised status (n = 34), the ORR was 8.8% (95% CI, 1.9-23.7). The median duration of response was 1.9 months (range, 1.3-2.1 months; 95% CI, 1.3-2.1). In the immunocompetent population, median PFS and overall survival were 3.0 months (95% CI, 2.5-6.0) and 5.3 months (95% CI, 4.3-6.0), respectively. CONCLUSIONS: The low response rates and limited durability confirm previous reports of the ineffectiveness of second-line or later chemotherapy in patients with metastatic MCC and provide a benchmark for assessing clinical benefit of new treatments.

Neoadjuvant imatinib in advanced primary or locally recurrent dermatofibrosarcoma protuberans: a multicenter phase II DeCOG trial with long-term follow-up.

PURPOSE: Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous tumor. COL1A1-PDGFB gene fusion is frequent in DFSP, rendering tumor cell proliferation and survival dependent on PDGFRß (platelet-derived growth factor receptor ß) signaling. This trial investigated imatinib as neoadjuvant treatment of DFSP, including long-term follow-up. EXPERIMENTAL DESIGN: The primary endpoint of this multicenter phase II trial was response; secondary endpoints were safety, tumor relapse, and response biomarkers. Patients with advanced primary or locally recurrent DFSP and measurable disease by RECIST (response evaluation criteria in solid tumors) were eligible and received imatinib 600 mg/d until definitive surgery with histopathologic proof of tumor-free margins. RESULTS: Sixteen patients received imatinib, and 14 patients were evaluable for all endpoints. Median treatment duration was 3.1 months; median tumor shrinkage was 31.5%. Best overall response was 7.1% complete response (CR), 50.0% partial response (PR), 35.7% stable disease, and 7.1% progressive disease (PD). Toxicity was moderate with 25.0% grade 3 and 4 events. During a median follow-up of 6.4 years, one patient developed secondary resistance to imatinib but responded to second-line sunitinib. This patient also presented local recurrence, distant metastasis, and death from DFSP. Exploratory analysis showed that response to imatinib was associated with decreased tumor cellularity and formation of strong hyalinic fibrosis. Weak PDGFRB phosphorylation and pigmented-type DFSP were associated with nonresponse. Additional to PDGFRB, the kinases EGFR and insulin receptor were found activated in a high percentage of DFSPs. CONCLUSION: The neoadjuvant use of imatinib 600 mg/d in DFSP is efficacious and well tolerated. Long-term follow-up results do not definitely support smaller surgical margins after successful imatinib pretreatment, and presume that secondary resistance to imatinib might promote accelerated disease progression.