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Purpose Angiosarcoma is a highly aggressive mesenchymal tumor. Although systemic chemotherapy is often considered for the inoperable or metastatic angiosarcoma, the outcome of such treatment is unsatisfactory and poorly delineated. Materials and Methods We reviewed electronic medical records of 75 patients with angiosarcoma who were treated with systemic chemotherapy for inoperable or metastatic disease. Patients were classified as having liver involvement if they had either primary or metastatic hepatic lesions. Results Among the patients evaluated, 51 patients (68%) were male and 24 patients (32%) had primary cutaneous angiosarcoma. Liver involvement was present in 28 patients (37.3%). A total of 59 patients received first-line weekly paclitaxel (wPac) and showed an objective response rate (ORR) of 23.7% (n=14), a median progression-free survival (mPFS) of 4.0 months (95% confidence interval [CI], 3.0 to 6.1), and a median overall survival (mOS) of 10.2 months (95% CI, 7.0 to 14.6). Among patients without liver involvement, patients receiving wPac (n=35) had significantly prolonged mPFS (5.8 months vs. 3.2 months, respectively; p=0.014) with a tendency for prolonged mOS (13.8 months vs. 11.6 months, respectively; p=0.13) than those receiving other regimens (n=12). A total of 24 patients received second- or later-line pazopanib monotherapy and showed an ORR of 16.7% (n=4), a mPFS of 2.4 months (95% CI, 1.8 to 4.3) and a mOS of 5.4 months (95% CI, 3.5 to not available). Conclusion Treatment with first-line wPac and later-line pazopanib seems to provide survival benefit, especially for patients with advanced angiosarcoma without liver involvement.