Intestinal Leiomyosarcoma Medication

  • Chief Editor: Julian Katz, MD   more...
 
Updated: Jan 7, 2010
 

Medication Summary

Imatinib mesylate (Gleevec), a 2-phenylaminopyridine that functions as a tyrosine kinase inhibitor, targets the c-kit domain expressed by some GISTs.[10] It has been shown to improve disease-free intervals in patients after resection of the tumor. A similar compound, sunitinib (Sutent), has been shown to be effective in patients with mutant GIST cells that are resistant to imatinib mesylate.[11]

Clinical trials are currently investigating agents, such as AP13573 and ET743, in patients with advanced leiomyosarcomas, liposarcomas, or osteosarcomas.

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Tyrosine kinase inhibitors

Class Summary

These agents inhibit the signal transduction pathway regulated by receptor tyrosine kinase.

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Imatinib mesylate (Gleevec)

 

Specifically designed to inhibit tyrosine kinase activity of bcr-abl kinase in GISTs. GISTs are characterized by expression of the product of the proto-oncogene c-kit and often harbor gain-of-function kit mutations, leading to ligand-independent kinase activation. Inhibits abl, kit, and platelet-derived growth factor receptor (PDGFR) tyrosine kinase.

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Sunitinib (Sutent)

 

Mulitkinase inhibitor that targets several tyrosine kinase inhibitors implicated in tumor growth, pathologic angiogenesis, and metastatic progression. Inhibits PDGFRs (ie, PDGFR-alpha, PDGFR-beta), vascular endothelial growth factor receptors (ie, VEGFR1, VEGFR2, VEGFR3), stem cell factor receptor (kit), Fms-like tyrosine kinase-3 (FLT3), colony-stimulating factor receptor type 1 (CSF-1R), and the glial cell-line–derived neurotrophic factor receptor (RET). Indicated for persons with GISTs whose disease has progressed or who are unable to tolerate treatment with imatinib mesylate (Gleevec). Delays median time to tumor progression.

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Contributor Information and Disclosures
Coauthor(s)

George Brasinikas, MD  Staff Physician, Department of Pathology, Birmingham Baptist Medical Center

George Brasinikas, MD is a member of the following medical societies: American Medical Association, College of American Pathologists, and Medical Association of the State of Alabama

Disclosure: Nothing to disclose.

Specialty Editor Board

Rajeev Vasudeva, MD, FACG  Clinical Professor of Medicine, Consultants in Gastroenterology, University of South Carolina School of Medicine

Rajeev Vasudeva, MD, FACG is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy, Columbia Medical Society, South Carolina Gastroenterology Association, and South Carolina Medical Association

Disclosure: Pricara Honoraria Speaking and teaching; UCB Consulting fee Consulting

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Noel Williams, MD  Professor Emeritus, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada; Professor, Department of Internal Medicine, Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada

Noel Williams, MD is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Alex J Mechaber, MD, FACP  Senior Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine

Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine

Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD  Clinical Professor of Medicine, Drexel University College of Medicine; Consulting Staff, Department of Medicine, Section of Gastroenterology and Hepatology, Hospital of the Medical College of Pennsylvania

Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law, Medicine & Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility

Disclosure: Nothing to disclose.

References

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  8. Yoshida S, Yamashita K, Yokozawa M, et al. Diagnostic findings of ultrasound-guided fine-needle aspiration cytology for gastrointestinal stromal tumors: proposal of a combined cytology with newly defined features and histology diagnosis. Pathol Int. Oct 2009;59(10):712-9. [Medline].

  9. Tien YW, Lee CY, Huang CC, Hu RH, Lee PH. Surgery for gastrointestinal stromal tumors of the duodenum. Ann Surg Oncol. Oct 20 2009;epub ahead of print. [Medline].

  10. D'Adamo D. Advances in the treatment of gastrointestinal stromal tumor. Adv Ther. Oct 2 2009;epub ahead of print. [Medline].

  11. Guo T, Hajdu M, Agaram NP, et al. Mechanisms of sunitinib resistance in gastrointestinal stromal tumors harboring KITAY502-3ins mutation: an in vitro mutagenesis screen for drug resistance. Clin Cancer Res. Nov 15 2009;15(22):6862-70. [Medline].

  12. Miki Y, Kurokawa Y, Hirao M, et al. Survival analysis of patients with duodenal gastrointestinal stromal tumors. J Clin Gastroenterol. Oct 3 2009;epub ahead of print. [Medline].

  13. Artigau Nieto E, Luna Aufroy A, et al. Gastrointestinal stromal tumors: experience in 49 patients. Clin Transl Oncol. Aug 2006;8(8):594-8. [Medline].

  14. Demetri GD, van Oosterom AT, Garrett CR, et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet. Oct 14 2006;368(9544):1329-38.

  15. Hines OJ, Nelson S, Quinones-Baldrich WJ, Eilber FR. Leiomyosarcoma of the inferior vena cava: prognosis and comparison with leiomyosarcoma of other anatomic sites. Cancer. Mar 1 1999;85(5):1077-83. [Medline].

  16. Yang WL, Yu JR, Wu YJ, et al. Duodenal gastrointestinal stromal tumor: clinical, pathologic, immunohistochemical characteristics, and surgical prognosis. J Surg Oncol. Dec 1 2009;100(7):606-10. [Medline].

  17. Zhan WH, Wang PZ, Shao YF, et al. [Efficacy and safety of adjuvant post-surgical therapy with imatinib in gastrointestinal stromal tumor patients with high risk of recurrence: interim analysis from a multicenter prospective clinical trial] [Chinese]. Zhonghua Wei Chang Wai Ke Za Zhi. Sep 2006;9(5):383-7. [Medline].

 
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Colonic mucosa with gastrointestinal stromal tumor (GIST) involving adjacent submucosa (hematoxylin and eosin [H&E] stain, medium power).
Clusters of tumor cells separated by a hyaline and mucin-rich stroma (hematoxylin and eosin [H&E] stain, medium power).
Oval- to spindle-shaped cells forming a fascicle (hematoxylin and eosin [H&E] stain, high power).
CD-34 stain showing a tumor (medium power). CD-34 is a myeloid progenitor cell antigen.
High-power magnification with CD-34 antigen immunohistochemical stain showing membrane positivity of tumor cells.
 
 
 
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