Combination chemotherapy for soft‐tissue sarcomas: A phase III study

Cruz, Anatolio B.; Thames, E. A.; Aust, J. Bradley; Metter, Gerald E.; Ramírez, Gema; Fletcher, William S.; Altman, Stanley J.; Frelick, Robert W.; Hill, George J.

doi:10.1002/jso.2930110406

Cited by 42 publications

(11 citation statements)

References 5 publications

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“…Dox is one of the oldest and most widely used antitumor drugs and has often been used in the clinic for the treatment of a broad spectrum of tumors . In addition, Dox was the first and remains the most active single chemotherapeutic agent in soft tissue sarcoma . In chondrosarcoma, systemic treatment with Dox has been shown to improve survival significantly compared with no treatment .…”

Section: Introductionmentioning

confidence: 99%

Basic fibroblast growth factor promotes doxorubicin resistance in chondrosarcoma cells by affecting XRCC5 expression

Hsieh

Huang

Lin

et al. 2020

Molecular Carcinogenesis

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Chondrosarcoma is the second most common form of bone cancer and is characterized by its ability to produce an extracellular matrix of the cartilage. High‐grade chondrosarcoma is highly aggressive and can metastasize to other parts of the body. Chondrosarcoma is resistant to both conventional chemotherapy and radiotherapy; hence, the current main treatment is still surgical resection. Doxorubicin (Dox) has been shown to significantly improve patient survival compared with untreated chondrosarcoma. However, for patients with metastasis, surgical resection alone can hardly treat them. In addition, drug resistance is one of the leading causes of death in patients with chondrosarcoma. Secreted proteins can mediate cell‐cell interactions in the cancer microenvironment, which may be associated with the development of drug resistance. In the present study, chondrosarcoma cells were treated with Dox, the conditioned medium was then collected and changes in secreted proteins were analyzed using the antibody array. Results showed that the Dox‐treated group had the highest secretion of basic fibroblast growth factor (bFGF), indicating the effect of bFGF on Dox sensitivity in chondrosarcoma. Furthermore, lentiviral‐mediated knockdown and treatment of exogenous recombinant protein were employed to further investigate the effect of bFGF on Dox resistance. Results demonstrated that bFGF can promote the expression of X‐ray repair cross‐complementing protein 5 (XRCC5), leading to Dox resistance. Secreted bFGF is likely to be detected in serum, in addition to being a biomarker for predicting Dox resistance, the combination of Dox and bFGF/XRCC5 blockers may be a new therapeutic strategy to improve the efficacy of Dox in future.

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Section: Introductionmentioning

confidence: 99%

Basic fibroblast growth factor promotes doxorubicin resistance in chondrosarcoma cells by affecting XRCC5 expression

Hsieh

Huang

Lin

et al. 2020

Molecular Carcinogenesis

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“…2-4 Doxorubin in combination with ifosfamide has been shown to produce higher response rates but without improvement in 1-year survival. 5 Median survival for those with metastatic disease remains poor at 8 to 12 months.…”

Section: Introductionmentioning

confidence: 99%

Phase II study of sunitinib malate, a multitargeted tyrosine kinase inhibitor in patients with relapsed or refractory soft tissue sarcomas. Focus on three prevalent histologies: Leiomyosarcoma, liposarcoma and malignant fibrous histiocytoma

Mahmood

Agresta

Vigil

et al. 2011

Intl Journal of Cancer

105

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SUMMARY Soft tissue sarcomas (STS) represent a diverse group of histologic subtypes with targetable molecular alterations, often treated as a single disease. Sunitinib malate is a multitargeted receptor tyrosine kinase inhibitor active in other solid tumors carrying similar alterations (i.e., imatinib mesylate-refractory gastrointestinal stromal tumors). This single-institution phase II study investigated the safety and efficacy of sunitinib malate in three common STS subtypes. Patients with documented unresectable or metastatic STS (liposarcoma, leiomyosarcoma, and malignant fibrous histiocytoma [MFH]), measurable disease, and 3 or less prior lines of therapy were eligible. Treatment consisted of sunitinib malate, 50 mg daily, for 4 weeks every 6 weeks. Forty-eight patients were enrolled, and 35% were heavily pretreated (≥2 prior lines of chemotherapy). The safety profile resembled previously known sunitinib malate toxicities. Median progression-free and overall survivals for liposarcoma, leiomyosarcoma, and MFH were 3.9 and 18.6, 4.2 and 10.1, and 2.5 and 13.6 months, respectively. The 3-month progression-free rates in the untreated and pretreated (chemotherapy) patients with liposarcoma, leiomyosarcoma, and MFH were 75% and 69.2%, 60%, and 62.5%, and and 25% and 44.4%, respectively. With the caveats that a minority of patients with potentially indolent or low-grade disease could have been included and the small numbers, a 3-month progression-free rate of >40% suggests activity for sunitinib malate at least in liposarcomas and leiomyosarcomas. Thus, we believe that further investigation in these susceptible STS subtypes is warranted.

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“…Five-year survival in patients with STS of all stages remains only 50%-60% [1,2]. Response rates for patients with late stage or recurrent disease are between 10% and 30%, with their median survival between 12 and 18 mo [3][4][5][6][7][8]. These patients are therefore appropriate candidates for investigational therapies.…”

Section: Introductionmentioning

confidence: 96%