Treatment
Current Options
Surgery Is Standard of Care for Resectable Primary GIST
Surgery remains the treatment of choice for primary resectable GIST. However, primary GISTs have a high risk of metastatic relapse after initial surgery for localised disease.1Surgery for metastatic or recurrent GIST is not curative: as at this stage the cancer has become a systemic disease. More than half of all GIST patients present with advanced GIST. Surgery alone is generally not curative: the 5-year survival rate after complete resection is variable and ranges from 50% to 65% for localised primary GIST and decreases to approximately 35% for advanced GIST.2
Several surgical principles apply to the management of patients with primary GIST. These principles include:2,3
- Complete gross resection of the tumour and pseudocapsule
- Thorough inspection of the peritoneal surfaces and liver to identify metastasis
- En bloc resection of adjacent tissue should GIST become adherent to nearby structures
- Wide margins are not necessary for disease clearance, but achievement of clear margins may require consideration of complete or partial organ sacrifice2,3
- Lymphadenectomy is generally not necessary because regional lymph node involvement is rare1
Surgery continues to be the therapy of choice in patients with resectable GIST. However, the curative potential of surgery is seldom realised due to a high rate of recurrence and a 5-year survival rate of approximately 54%.4
Glivec: Effective Systemic Therapy Becomes the Standard of Care for Advanced GIST
The management of patients with GIST has evolved dramatically since the introduction of Glivec® (imatinib) in 2002. Before this, nonspecific chemotherapy, surgery, and radiation therapy were the only modalities available. While surgery remains the therapy of choice in resectable tumours, the role of chemotherapy and radiation therapy has been limited by a lack of efficacy and intolerable toxicity.
Glivec is a potent inhibitor of several tyrosine kinases that are commonly associated with GIST, such as KIT and PDGFR. Clinical trial results have shown Glivec to be effective and safe in the management of unresectable and/or malignant metastatic GIST. At 52-month follow-up of the pivotal phase 2 B2222 trial, 84% of patients had a best response of stable disease or better: 2 patients (1%) achieved complete response, 98 patients (67%) achieved partial response, and 23 patients (16%) achieved stable disease.5,6 Current guidelines recommend continued use of Glivec until progression, intolerance, or patient refusal1. A treatment algorithm for patients diagnosed with GIST delineates optimal management of patients with GIST and Glivec7, including:
- Initial treatment of metastatic or inoperable GIST with 400 mg or 600 mg Glivec
- Potential dose escalation of Glivec to 800 mg upon disease progression
- Clinical trials of Glivec as adjuvant or neoadjuvant treatment for GIST
- Clinical trials of Glivec therapy as part of a combination regimen or newer targeted agents upon disease progression at 800 mg dose of Glivec
Figure 1. Treatment Algorithm for Patients Diagnosed With Confirmed GIST7
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References:
1. Blay JY, Bonvalot S, Casali P, et al. Consensus meeting for the management of gastrointestinal stromal tumors. Report of the GIST Consensus Conference of 20-21 March 2004, under the auspices of European Society for Medical Oncology. Ann Oncol. 2005;16:566-578.
2. Eisenberg BL, Judson I. Surgery and imatinib in the management of GIST: emerging approaches to adjuvant and neoadjuvant therapy. Ann Surg Oncol. 2004;11:464-475.
3. Demetri G, Benjamin R, Blanke CD, et al. NCCN Task Force Report: optimal management of patients with gastrointestinal stromal tumor (GIST)--expansion and update of NCCN Clinical Practice Guidelines. J Natl Compr Canc Netw. 2004;2(suppl 1):S1-S26.
4. DeMatteo RP, Lewis JJ, Leung D, Mudan SS, Woodruff JM, Brennan MF. Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann Surg. 2000;231:51-58.
5. Demetri G, von Mehren M, Joensuu H, et al. Long-term clinical outcomes of imatinib treatment in patients with advanced gastrointestinal stromal tumors. J Clin Oncol. Manuscript submitted.
6. Blanke CD, Demetri G, von Mehren M, et al. Long-term follow-up of a phase II randomized trial in advanced gastrointestinal stromal tumor (GIST) patients (pts) treated with imatinib mesylate [abstract]. J Clin Oncol. 2006;24:526s. Abstract 9528.
7. Reichardt P. Optimising therapy for GIST patients. Eur J Cancer. 2006;4(suppl 1):19-26.