Metastatic Alveolar Soft Part Sarcoma Responsive to Pazopanib after Progression through Sunitinib and Bevacizumab: Two Cases

Read, William; Williams, Cecilia

doi:10.1159/000450545

Cited by 12 publications

(15 citation statements)

References 17 publications

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“…Therefore, due to the pathophysiology and vascular nature of this tumor, novel therapeutic agents such as tyrosine kinase receptor inhibitors or antiangiogenic therapy are considered a rational approach for this disease . Recently, agents such as cediranib, sunitinib, dasatinib, pazopanib, and tivantinib have been used in ASPS with promising results. In Table , we summarize the results of reports regarding targeted therapy for ASPS including the current series .…”

Section: Discussionmentioning

confidence: 99%

“…It is difficult to assess clinical benefit in ASPS as the rate of tumor growth is variable, and patients may have prolonged periods of SD without any treatment. There are reports of multiple targeted agents used one at a time in the same patient following each disease progression to achieve increased survival . Cediranib, a potent inhibitor of all three VEGFRs, may be considered a reasonable first choice for patients with metastatic disease as it has the greatest adult experience and best‐documented outcome.…”

Section: Discussionmentioning

confidence: 99%

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Alveolar soft part sarcoma in children and young adults: A report of 69 cases

Flores

Harrison

Federman³

et al. 2018

Pediatric Blood & Cancer

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Alveolar soft part sarcoma in children and young adults: A report of 69 cases

Flores

Harrison

Federman³

et al. 2018

Pediatric Blood & Cancer

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“…Pazopanib shares many tyrosine kinase targets with sunitinib, including those in the VEGF and platelet-derived growth factor (PDGF) pathways. William, et al reported on two metastatic ASPS patients for whom sunitinib treatment resulted in stable disease lasting more than one year [ 38 ]. Following subsequent disease progression (after sunitinib and second-line bevacizumab), both patients again achieved disease stabilization with pazopanib treatment.…”

Section: Discussionmentioning

confidence: 99%

Advanced alveolar soft part sarcoma responds to apatinib

et al. 2017

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Alveolar soft part sarcoma (ASPS) is a rare, hypervascular soft tissue sarcoma with a low chemotherapy response rate. Here, we report an ASPS case with multiple lung metastases on initial presentation. The primary tumor, a hypervascular soft tissue mass 4.1×3.2×2.0 cm, located in the right thigh, was resected prior to chemotherapy. The patient suffered disease progression after two cycles of gemcitabine-docetaxel treatment. Immunohistochemical examination of the tumor tissue revealed strong positive staining for vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2). The patient was subsequently treated with apatinib (500 mg/day), a specific VEGFR-2 inhibitor. Treatment was well tolerated, and the patient exhibited a partial response, with the lung metastases reduced in size and number after one month of therapy. To date, 12-month progression-free survival has been achieved. Apatinib may provide an additional treatment option for metastatic ASPS, particularly in cases resistant to other chemotherapeutic options. Furtherstudies with more cases with longer follow-up times will be necessary to determine the clinical efficacy of apatinib for treatment of ASPS.

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“…Pazopanib was recently approved by the U.S. Food and Drug Administration (FDA) for the clinical treatment of advanced soft tissue sarcoma. Pazopanib is a novel TK inhibitor (TKI) that targets PDGFR, VEGFR, and c-kit [ 23 – 26 ]. Some published studies have reported acceptable response rates of ASPS to treatment with pazopanib, despite the low response rates observed with most types of soft tissue sarcoma (STS) [ 23 – 26 ].…”

Section: Introductionmentioning

confidence: 99%

“…Pazopanib is a novel TK inhibitor (TKI) that targets PDGFR, VEGFR, and c-kit [ 23 – 26 ]. Some published studies have reported acceptable response rates of ASPS to treatment with pazopanib, despite the low response rates observed with most types of soft tissue sarcoma (STS) [ 23 – 26 ]. However, the mechanisms of action of pazopanib and the responses to the drug in ASPS tumor cell lines have not yet been explored.…”

Section: Introductionmentioning

confidence: 99%

Cabozantinib and dastinib exert anti-tumor activity in alveolar soft part sarcoma

et al. 2017

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BackgroundAlveolar soft part sarcoma (ASPS) is an extremely rare metastatic soft tissue tumor with a poor prognosis for which no effective systemic therapies have yet been established. Therefore, the development of novel effective treatment approaches is required. Tyrosine kinases (TKs) are being increasingly used as therapeutic targets in a variety of cancers. The purpose of this study was to identify novel therapeutic target TKs and to clarify the efficacy of TK inhibitors (TKIs) in the treatment of ASPS.Experimental designTo identify novel therapeutic target TKs in ASPS, we evaluated the antitumor effects and kinase activity of three TKIs (pazopanib, dasatinib, and cabozantinib) against ASPS cells using an in vitro assay. Based on these results, we then investigated the phosphorylation activities of the identified targets using western blotting, in addition to examining antitumor activity through in vivo assays of several TKIs to determine both the efficacy of these substances and accurate targets.ResultsIn cell proliferation and invasion assays using pazopanib, cabozantinib, and dasatinib, all three TKIs inhibited the cell growth in ASPS cells. Statistical analyses of the cell proliferation and invasion assays revealed that dasatinib had a significant inhibitory effect in cell proliferation assays, and cabozantinib exhibited marked inhibitory effects on cellular functions in both assays. Through western blotting, we also confirmed that cabozantinib inhibited c-MET phosphorylation and dasatinib inhibited SRC phosphorylation in dose-dependent fashion. Mice that received cabozantinib and dasatinib had significantly smaller tumor volumes than control animals, demonstrating the in vivo antitumor activity of, these substances.ConclusionsOur findings suggest that cabozantinib and dasatinib may be more effective than pazopanib against ASPS cells. These in vitro and in vivo data suggest that c-MET may be a potential therapeutic target in ASPS, and cabozantinib may be a particularly useful therapeutic option for patients with ASPS, including those with pazopanib-resistant ASPS.

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Metastatic Alveolar Soft Part Sarcoma Responsive to Pazopanib after Progression through Sunitinib and Bevacizumab: Two Cases

Cited by 12 publications

References 17 publications

Alveolar soft part sarcoma in children and young adults: A report of 69 cases

Alveolar soft part sarcoma in children and young adults: A report of 69 cases

Advanced alveolar soft part sarcoma responds to apatinib

Cabozantinib and dastinib exert anti-tumor activity in alveolar soft part sarcoma

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