Imatinib mesylate in soft tissue and bone sarcomas: Interim results of a Sarcoma Alliance for Research thru Collaboration (SARC) phase II trial

Chugh, Rashmi; Thomas, Dominic; Wathen, K.; Thall, Peter F.; Benjamin, Robert S.; Maki, Robert G.; Samuels, Brian L.; Keohan, Mary Louise; Priebat, Dennis A.; Baker, Laurence H.

doi:10.1200/jco.2004.22.14_suppl.9001

Cited by 12 publications

(10 citation statements)

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“…Chugh et al [35] presented interim results of a Sarcoma Alliance for Research through Collaboration (SARC) phase II trial earlier this year. After prior therapy, 181 patients with nine sarcoma subtypes and progressive disease were enrolled and received imatinib mesylate at doses 100 to 300 mg twice daily (BID [35]. The 20% progression-free interval in leiomyosarcoma suggests that further study in this uterine malignancy is warranted.…”

Section: Imatinib Mesylate In Sarcomamentioning

confidence: 97%

“…Of 104 evaluable patient responses, 0 complete responses (CRs), two partial responses (PRs), 23 patients with stable disease (SD), and 79 patients with progressive disease (PD) were noted [34]. Chugh et al [35] presented interim results of a Sarcoma Alliance for Research through Collaboration (SARC) phase II trial earlier this year. After prior therapy, 181 patients with nine sarcoma subtypes and progressive disease were enrolled and received imatinib mesylate at doses 100 to 300 mg twice daily (BID [35].…”

Section: Imatinib Mesylate In Sarcomamentioning

confidence: 99%

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Imatinib mesylate and its potential implications for gynecologic cancers

Dushkin¹,

Schilder

2005

Curr. Treat. Options in Oncol.

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Among gynecologic malignancies, ovarian carcinoma is the most frequent cause of death, with the majority of patients presenting at advanced stage. There is a high rate of recurrence despite first-line chemotherapy. Sarcoma of the uterus, while accounting for a small percent of uterine cancers, is also associated with a high-recurrence rate and poor overall survival. Therefore, the development of novel treatment strategies is paramount. Imatinib mesylate (Gleevec; Novartis Pharmaceuticals Corp., East Hanover, NJ) is a tyrosine kinase inhibitor with activity against abl, c-kit, and platelet derived growth factor receptor (PDGFR), and is approved for the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumor. Preclinical data provides evidence for c-kit and PDGFR expression in ovarian epithelial carcinomas and uterine sarcomas and have led to clinical trials evaluating the use of imatinib in these malignancies. Additionally, inhibition of PDGFR signaling has been proposed as an effective mechanism of chemotherapy by lowering tumor interstitial fluid pressure. Recent data have also suggested benefit with metronomic scheduling of cytotoxic agents at lower doses at more frequent dosing intervals, in combination with other targeted therapies. While activity of this agent remains to be established, further studies of imatinib in gynecologic malignancies are warranted, to demonstrate not only single-agent activity and the enhancement of cytotoxicity of other antineoplastic agents.

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Section: Imatinib Mesylate In Sarcomamentioning

confidence: 97%

Section: Imatinib Mesylate In Sarcomamentioning

confidence: 99%

Imatinib mesylate and its potential implications for gynecologic cancers

Dushkin¹,

Schilder

2005

Curr. Treat. Options in Oncol.

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“…SARC investigated also the activity of imatinib against unresectable or difficult to resect desmoid tumors. Two and four months progression-free survival in 22 evaluable patients were 91% and 78%, respectively; polymorphisms/mutations of the platelet-derived growth factor receptor (PDGFR) alpha exon 18 were found and responsiveness might be a function of the alteration of that gene or other downstream effectors [87]. Imatinib has produced also responses in chemotherapy-resistant locally advanced or metastatic dermatofibrosarcoma protuberans, due to its inhibition of the PDGFR tyrosine kinase.…”

Section: Imatinibmentioning

confidence: 98%

New emerging drugs in soft tissue sarcoma

Milano

Apice

Ferrari

et al. 2006

Critical Reviews in Oncology/Hematology

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“…20 In this light, the existing data, suggesting that imatinib, when applied alone, is not effective in ESFT patients 21 should be reevaluated.…”

Section: Discussionmentioning

confidence: 99%

Evidence for activation of KIT, PDGFRα, and PDGFRβ receptors in the Ewing sarcoma family of tumors

Bozzi

Tamborini

Negri

et al. 2007

Cancer

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BACKGROUND. The Ewing sarcoma family of tumors (ESFT) is one of the most common malignant neoplasms of children and adolescents, characterized by nonrandom translocations involving the Ewing sarcoma (EWS) gene. Over the years the adoption of intensive multimodality treatment approaches has led to a gradual improvement in the survival of patients with ESFT. The prognosis is still unsatisfactory for high‐risk patients, however, and novel therapeutic approaches are desirable. The aim of the study was to investigate the expression/activation of KIT, PDGFRα, and PDGFRβ receptor tyrosine kinases (RTKs) as potential therapeutic targets in ESFT. METHODS. RNA and proteins were extracted from 20 frozen ESFT specimens to ascertain the state activation of KIT, PDGFRα, and PDGFRβ. RESULTS. No mutations were found, whereas the cognate ligands were detected in all cases by polymerase chain reaction (PCR). The expression and activation of KIT, PDGFRα, and PDGFRβ were confirmed by quantitative PCR, immunohistochemistry, and immunoprecipitation and/or Western blot analysis. In particular, when compared with a protein pool obtained from normal adult tissues, PDGFRβ showed a greater protein expression and/or a stronger phosphorylation signal. CONCLUSIONS. The results are consistent with an autocrine/paracrine loop activation of the KIT, PDGFRα, and PDGFRβ receptors and suggest a rationale for the use of RTK inhibitors, either alone or in combination with chemotherapy. Cancer 2007. © 2007 American Cancer Society.

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Imatinib mesylate in soft tissue and bone sarcomas: Interim results of a Sarcoma Alliance for Research thru Collaboration (SARC) phase II trial

Cited by 12 publications

References 0 publications

Imatinib mesylate and its potential implications for gynecologic cancers

Imatinib mesylate and its potential implications for gynecologic cancers

New emerging drugs in soft tissue sarcoma

Evidence for activation of KIT, PDGFRα, and PDGFRβ receptors in the Ewing sarcoma family of tumors

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