eMedicine Specialties > Gastroenterology > Intestine

Intestinal Leiomyosarcoma: Treatment & Medication

Author: Richard K Spence, MD, Senior Vice President for Clinical Affairs, Infonale
Coauthor(s): George Brasinikas, MD, Staff Physician, Department of Pathology, Birmingham Baptist Medical Center
Contributor Information and Disclosures

Updated: Nov 9, 2006

Treatment

Medical Care

Chemotherapy and radiation have shown only limited benefit in the treatment of leiomyosarcomas. Response rates to various chemotherapeutic regiments generally have been below 40%.

Surgical Care

Resection of the tumor is the only hope for cure. Remove associated lymph nodes, but extended lymphadenectomy is not necessary because these tumors rarely metastasize to lymph nodes (see Pathophysiology).

Consultations

  • A gastroenterologist probably will be involved in most of these cases because patients generally present with gastrointestinal bleeding.
    • Endoscopic ultrasound may be of some benefit for diagnosing the more proximal tumors.
    • Also, if ulceration occurs, performing a biopsy may be possible.
  • A surgeon must be involved to provide the definitive treatment.
  • A hematologist/oncologist may be able to provide insights into the prognosis and define the grade of the tumor.

Medication

Imatinib mesylate (Gleevec), a 2-phenylaminopyridine that functions as a tyrosine kinase inhibitor, targets the c-kit domain expressed by some GIST tumors. 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.

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

Tyrosine kinase inhibitors

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


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.

Adult

400 mg PO qd with food; may increase to 800 mg/d divided bid in absence of adverse effects

Pediatric

Not established

CYP3A4 inhibitors (ketoconazole increases distribution of imatinib mesylate); CYP3A4 substrates (simvastatin increases maximum concentration of imatinib mesylate by a 2-3.5-fold factor); CYP3A4 inducers (phenytoin decreases AUC by approximately one fifth of typical AUC); likely to increase blood levels of drugs that are substrates of CYP2C9, CYP2D6, and CYP3A4/5

Pregnancy

D - Unsafe in pregnancy

Precautions

Dose must be reduced or interrupted if edema or anemia occur, transaminases or bilirubin levels become elevated, or grade 3-4 neutropenia or thrombocytopenia develop; pediatric patients commonly experience musculoskeletal pain


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.

Adult

Standard dose: 50 mg PO qd on a schedule of 4 wk on treatment, followed by 2 wk off treatment, then repeat cycle
Dose modification: Increase or reduce dose in 12.5-mg increments based on individual safety and tolerability
Coadministration with potent CYP4503A4 inhibitors: Minimum dose of 37.5 mg PO qd during treatment phase of cycle
Coadministration with CYP4503A4 inducers: Maximum dose of 87.5 mg PO qd during treatment phase of cycle

Pediatric

Not established

Potent CYP4503A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) may increase plasma concentrations; CYP4503A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, phenobarbital) may decrease plasma concentrations; St John's wort induces metabolism and decreases plasma concentrations unpredictably (do not take concurrently)

Documented hypersensitivity; concurrent administration with St John's wort

Pregnancy

D - Unsafe in pregnancy

Precautions

Common adverse effects include diarrhea, skin discoloration, mouth irritation, weakness, and altered taste; may cause fatigue, hypertension, bleeding, swelling, and hypothyroidism; in clinical trials, decreased left ventricular ejection fraction to below lower limits of normal in 15% of patients (monitor for CHF and discontinue if clinical manifestations of CHF develop); may cause hemorrhagic events that may include epistaxis or rectal, gingival, GI, genital, or wound bleeding

More on Intestinal Leiomyosarcoma

Overview: Intestinal Leiomyosarcoma
Differential Diagnoses & Workup: Intestinal Leiomyosarcoma
Treatment & Medication: Intestinal Leiomyosarcoma
Follow-up: Intestinal Leiomyosarcoma
Multimedia: Intestinal Leiomyosarcoma
References
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References

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

  2. 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.

  3. Evans HL. Smooth muscle tumors of the gastrointestinal tract. A study of 56 cases followed for a minimum of 10 years. Cancer. Nov 1 1985;56(9):2242-50. [Medline].

  4. Hill MA, Mera R, Levine EA. Leiomyosarcoma: a 45-year review at Charity Hospital, New Orleans. Am Surg. Jan 1998;64(1):53-60; discussion 60-1. [Medline].

  5. 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].

  6. Ludwig DJ, Traverso LW. Gut stromal tumors and their clinical behavior. Am J Surg. May 1997;173(5):390-4. [Medline].

  7. Martin RG. Malignant tumors of the small intestine. Surg Clin North Am. Aug 1986;66(4):779-85. [Medline].

  8. Zhan J, Xia ZS, Zhong YQ, et al. Clinical analysis of primary small intestinal disease: A report of 309 cases. World J Gastroenterol. Sep 1 2004;10(17):2585-7. [Medline].

  9. 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 [in Chinese]. Zhonghua Wei Chang Wai Ke Za Zhi. Sep 2006;9(5):383-7.

  10. Zhou PH, Yao LQ, Zhong YS, et al. Role of endoscopic miniprobe ultrasonography in diagnosis of submucosal tumor of large intestine. World J Gastroenterol. Aug 15 2004;10(16):2444-6. [Medline].

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Further Reading

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Keywords

gut stromal tumors, gastrointestinal stromal tumors, GISTs

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Contributor Information and Disclosures

Author

Richard K Spence, MD, Senior Vice President for Clinical Affairs, Infonale
Richard K Spence, MD is a member of the following medical societies: American Association of Blood Banks, American College of Physician Executives, American College of Surgeons, American Federation for Clinical Research, American Medical Association, American Medical Writers Association, American Society for Artificial Internal Organs, American Society for Parenteral and Enteral Nutrition, American Venous Forum, Association for Academic Surgery, Association for Surgical Education, Biomedical Engineering Society, Eastern Vascular Society, International College of Angiology, Medical Society of New Jersey, Medical Society of the State of New York, New York Academy of Sciences, Pan-Pacific Surgical Association, Peripheral Vascular Surgery Society, Shock Society, Society for Clinical Vascular Surgery, Society for Experimental Biology and Medicine, Society for Surgery of the Alimentary Tract, Society for Vascular Surgery, Society of Critical Care Medicine, Society of University Surgeons, Southeastern Surgical Congress, Surgical Infection Society, Transplantation Society, and Wound Healing Society
Disclosure: Nothing to disclose.

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.

Medical Editor

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, and South Carolina Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

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.

CME Editor

Alex J Mechaber, MD, FACP, Assistant Dean for Medical Curriculum, Associate Professor of Medicine, Division of General Internal 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 and Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

 
 
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