Phase II study of sunitinib malate (SM) in subjects with metastatic and/or surgically unresectable non-GIST soft tissue sarcomas

Vigil, C. E.; Chiappori, Alberto; Williams, C. A.; Shrager, H. H.; Murray, Bronwyn; Letson, Douglas; Sullivan, Dan M.; Garrett, Christopher R.; D’Amato, Gina Z.; Agresta, Samuel V.

doi:10.1200/jco.2008.26.15_suppl.10535

Cited by 14 publications

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“…In phase 2 trials, sunitinib yielded low ORR (2-3%), but stabilized disease in 20% of patients in one study and 80.6% in the other [99,100]. Interestingly, one of these studies compared ORR according to Response Evaluation Criteria in Solid Tumors (RECIST) with metabolic criteria.…”

Section: Targeted Therapiesmentioning

confidence: 99%

Systematic Therapy for Unresectable or Metastatic Soft-Tissue Sarcomas: Past, Present, and Future

Morgan

Cranmer

2011

Curr Oncol Rep

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Unresectable or metastatic disease occurs in 40% to 60% of soft-tissue sarcoma (STS) patients and portends a poor prognosis. For decades, doxorubicin has formed the backbone of systemic treatment, with response rates of approximately 26%. Patients progressing following first-line therapy were left with few proven options. No other cytotoxic chemotherapy agent or combination has demonstrated superiority to doxorubicin. Advances in targeted therapy of STS have been hindered by STS heterogeneity and poorly understood disease biology. Despite challenges, progress has been made in specific STS subtypes. Here, we highlight the challenges, progress, and lessons learned from STS trials published in the last 20 to 25 years.

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Section: Targeted Therapiesmentioning

confidence: 99%

Systematic Therapy for Unresectable or Metastatic Soft-Tissue Sarcomas: Past, Present, and Future

Morgan

Cranmer

2011

Curr Oncol Rep

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“…This property is not shared by imatinib. The RR to sunitinib has been evaluated in 36 patients with nongastroinstestinal stromal tumor (non‐GIST) STS (12 LMS, 12 LPS, 11 MFH, 1 fibrosarcoma) 19. The drug was well tolerated, although 1 patient developed congestive heart failure, and 1 patient developed pulmonary emboli.…”

Section: Inhibitors Of Angiogenesismentioning

confidence: 99%

Antiangiogenesis agents in the treatment of soft tissue sarcomas

Ganjoo

Jacobs

2010

Cancer

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Soft tissue sarcomas (STSs) are a heterogeneous group of malignancies that includes >50 different subtypes, each with unique clinical and pathologic qualities. In general, there is a 50% cure rate, and most cures are achieved with complete surgical resection with or without radiation therapy. The results from chemotherapeutic agents for unresectable or metastatic disease have been disappointing with minimal long-term benefit. New targeted and novel agents are needed to improve response and survival. Tumor angiogenesis has been an intense focus in cancer therapy over the past decade. Several of numerous antiangiogenesis agents have been developed, and many already have been approved for the treatment of both solid and liquid tumors. Certain STSs are highly vascular tumors that often demonstrate angiogenesis markers. The objective of this review was to evaluate these angiogenesis markers in defining the role of angiogenesis in the treatment of patients with STS. In addition, the authors conducted an indepth review of the results from using key antiangiogenesis agents in the treatment of STS. Cancer 2010;116:1177-83. V C 2010 American Cancer Society.KEYWORDS: soft tissue sarcoma, angiogenesis, vascular endothelial growth factor, microvessel density, bevacizumab.Soft tissue sarcomas (STSs) are tumors of mesenchymal origin with more than 50 different subtypes. These tumors are uncommon, and the mainstay of treatment is complete surgical resection, with or without radiation therapy, which results in a 50% cure rate. The outcome for patients with unresectable or metastatic disease, however, is unacceptably poor. Chemotherapeutic agents result in short-lived responses and generally do not improve survival. Novel and targeted agents are needed to improve the outcome of these patients.It has been demonstrated that angiogenesis plays an important role in the growth and metastasis of several solid tumors. The response rates (RRs) to single-agent angiogenesis inhibitors generally are low; however, in combination with chemotherapy, these agents have produced improvements in overall survival in several solid tumors, including colon cancer and lung cancer.1,2 Several of these agents have been approved for the treatment of cancer over the past decade. Angiogenesis markers can aid in defining the importance of angiogenesis in each tumor type, and several surrogate markers of angiogenesis have been evaluated extensively.3 In this report, we update implications of these markers for outcome and review current clinical trials with antiangiogenesis agents. Tumor VascularityMicrovessel density (MVD) is 1 of the first markers of angiogenesis that seem to correlate with outcome in some solid tumors. However, the value of MVD as a prognostic factor in STS is controversial. Comandone and colleagues correlated MVD and survival in 45 patients with extremity STS, mostly liposarcoma (LPS) and malignant fibrous histiocytoma (MFH).4 At a median follow-up of 23 months, patients who had low MVD had improved median disease-free survival (DFS) (24 m...

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“…Some preliminary results from Phase II clini cal trials evaluating other TKIs, sunitinib [58][59][60] and sorafenib [61,62], in advanced STS found a disappointing low response rate by the Response Evaluation Criteria In Solid Tumors (RECIST) but interesting rates of stable disease by RECIST and responses following Choi's criteria, especially for some subgroups, such as leiomyosarcoma and angiosarcoma.…”

Section: Phase II Monotherapymentioning

confidence: 99%

Pazopanib: An Antiangiogenic Drug in Perspective

Castañeda

Gómez

2009

Future Oncol.

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Pazopanib, a tyrosine kinase inhibitor targeted to angiogenesis, has been tested in preclinical and clinical trials and has shown promising activity against a variety of solid tumors, such as renal cancer, all of which are related to the angiogenic pathway. It has a safety profile related to this mechanism of action. Diarrhea, hypertension, hair depigmentation and nausea are the most common side effects. Pazopanib is currently under evaluation as monotherapy and in combination with some potentially synergistic agents of proven activity.

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Phase II study of sunitinib malate (SM) in subjects with metastatic and/or surgically unresectable non-GIST soft tissue sarcomas

Cited by 14 publications

References 0 publications

Systematic Therapy for Unresectable or Metastatic Soft-Tissue Sarcomas: Past, Present, and Future

Systematic Therapy for Unresectable or Metastatic Soft-Tissue Sarcomas: Past, Present, and Future

Antiangiogenesis agents in the treatment of soft tissue sarcomas

Pazopanib: An Antiangiogenic Drug in Perspective

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