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      Efficacy of pazopanib monotherapy in patients who had been heavily pretreated for metastatic soft tissue sarcoma: a retrospective case series

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          Abstract

          Background

          We retrospectively reviewed outcomes of treatment with pazopanib, an oral multi-tyrosine kinase angiogenesis inhibitor, in patients with advanced soft tissue sarcoma, a rare and heterogeneous tumor group with limited treatment options.

          Methods

          Between 2009 and 2013, 43 patients with metastatic soft tissue sarcoma received pazopanib as salvage chemotherapy after one or more cytotoxic regimens. Response rate, progression-free survival, and overall survival were analyzed according to histological subtype, Eastern Cooperative Oncology Group performance status, and metastatic site.

          Results

          Common histological subtypes included leiomyosarcoma (n = 9), angiosarcoma (n = 6), malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma (MFH/UPS, n = 5), malignant peripheral nerve sheath tumor (MPNST, n = 5), and synovial sarcoma (n = 4). Nineteen patients (44.2%) received more than two chemotherapy regimens before pazopanib. At the time of analysis, 208 treatment cycles of pazopanib had been administered (median, 4.8 cycles per patient), and no treatment-related mortality occurred. The disease control rate was 61.0% (95% confidence interval [CI], 46.1–75.9%), and the overall response rate was 17.1% (partial response, n = 7; complete response, n = 0). Partial response was achieved in two patients with synovial sarcoma, two with MFH/UPS, one with MPNST, one with leiomyosarcoma, and one with angiosarcoma. The median lengths of progression-free survival and overall survival were 5.0 months (95% CI, 3.6–6.4 months) and 8.2 months (95% CI, 5.8–10.6 months), respectively. Progression-free survival was shorter in the patients with liposarcoma and rhabdomyosarcoma (1.3 and 0.9 months, respectively) than in those with leiomyosarcoma, MPNST, MFH/UPS, and synovial sarcoma (5.6, 6.5, 7.1, and 7.7 months, respectively).

          Conclusions

          Pazopanib demonstrated acceptable antitumor activity in the Asian patients who had been heavily pretreated for sarcoma, with seemingly more favorable results in the patients with leiomyosarcoma, MPNST, MFH/UPS, and synovial sarcoma than in those with liposarcoma and rhabdomyosarcoma.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12885-015-1160-x) contains supplementary material, which is available to authorized users.

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          Most cited references16

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          Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial.

          Effective targeted treatment is unavailable for most sarcomas and doxorubicin and ifosfamide-which have been used to treat soft-tissue sarcoma for more than 30 years-still have an important role. Whether doxorubicin alone or the combination of doxorubicin and ifosfamide should be used routinely is still controversial. We assessed whether dose intensification of doxorubicin with ifosfamide improves survival of patients with advanced soft-tissue sarcoma compared with doxorubicin alone.
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            Soft-tissue sarcomas in adults.

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              Phase II trial of weekly paclitaxel for unresectable angiosarcoma: the ANGIOTAX Study.

              The objective of this phase II trial was to assess the efficacy and toxicity of weekly paclitaxel for patients with metastatic or unresectable angiosarcoma. Thirty patients were entered onto the study from April 2005 through October 2006. Paclitaxel was administered intravenously as a 60-minute infusion at a dose of 80 mg/m(2) on days 1, 8, and 15 of a 4-week cycle. The primary end point was the nonprogression rate after two cycles. The progression-free survival rates after 2 and 4 months were 74% and 45%, respectively. With a median follow-up of 8 months, the median time to progression was 4 months and the median overall survival was 8 months. The progression-free survival rate was similar in patients pretreated with chemotherapy and in chemotherapy-naïve patients (77% v 71%). Three patients with locally advanced breast angiosarcoma presented partial response, which enabled a secondary curative-intent surgery with complete histologic response in two cases. One toxic death occurred as a result of a thrombocytopenia episode. Six patients presented with grade 3 toxicities and one patient presented with a grade 4 toxicity. Anemia and fatigue were the most frequently reported toxicities. Weekly paclitaxel at the dose schedule used in the current study was well tolerated and demonstrated clinical benefit.
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                Author and article information

                Contributors
                dr.kyleu@gmail.com
                HYOSONG77@yuhs.ac
                ssjj.lee@samsung.com
                sh1767.park@samsung.com
                kimhyj.kim@samsung.com
                KSHPATH@yuhs.ac
                yla.choi@samsung.com
                qshin@yuhs.ac
                CHOISIDORU@yuhs.ac
                jyunlee@skku.edu
                rha7655@yuhs.ac
                Journal
                BMC Cancer
                BMC Cancer
                BMC Cancer
                BioMed Central (London )
                1471-2407
                19 March 2015
                19 March 2015
                2015
                : 15
                : 154
                Affiliations
                [ ]Division of Hematology and Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 135-710 Republic of Korea
                [ ]Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-Gu, Seoul 120-752 Republic of Korea
                [ ]Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
                [ ]Department of Pathology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
                [ ]Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
                [ ]Department of Orthopedic Surgery, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
                Article
                1160
                10.1186/s12885-015-1160-x
                4438639
                25885855
                a87162c3-eebb-4c10-8b2e-600e0f974dc9
                © Yoo et al.; licensee BioMed Central. 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 16 October 2014
                : 4 March 2015
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2015

                Oncology & Radiotherapy
                histological type,pazopanib,soft tissue sarcoma
                Oncology & Radiotherapy
                histological type, pazopanib, soft tissue sarcoma

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