Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 3/2007

01-03-2007

Kinase Mutations and Imatinib Mesylate Response for 64 Taiwanese with Advanced GIST: Preliminary Experience from Chang Gung Memorial Hospital

Authors: Chun-Nan Yeh, MD, Tsung-Wen Chen, MD, Hsiang-Lin Lee, MD, Yu-Yin Liu, MD, Tzu-Chieh Chao, MD, PhD, Tsann-Long Hwang, MD, FACS, Yi-Yin Jan, MD, FACS, Miin-Fu Chen, MD, FACS

Published in: Annals of Surgical Oncology | Issue 3/2007

Login to get access

Abstract

Purpose

Most gastrointestinal stromal tumors (GISTs) express constitutively activated mutation of kit or platelet-derived growth factor receptor alpha (PDGFRA), which are therapeutic targets for imatinib. Results of 64 Taiwanese with advanced GIST treated with imatinib were reported.

Method and materials

Between 2001 and May 2006, a prospective, non-randomized, and a single center trial containing 64 Taiwanese patients with advanced GIST treated with imatinib was conducted. Each tumor was investigated for mutations of kit or PDGFRA.

Results

The median follow-up time after imatinib administration was 16.1 months. 12 patients (18.8%) had complete response (CR), 24 (37.5%) had a partial response (PR), 12 stationary disease (18.8%), 16 progressive disease (25.0%). The 64 Taiwanese with advanced GIST had an estimated median survival of 48.0 months and 4-year survival rate for 76.1%. Kit mutation was found in 49 of 54 (90.7%) test patients and five of them had no mutation (9.3%). No PDGFRA mutant was identified. In 40 patients harboring kit exon 11 mutations, the CR and PR rates (ORR) were 57.5% , nine patients with tumors containing kit exon 9 mutation had ORR rates of 22.2%, and five patients with no mutation had ORR rates of 60.0% (not significant; P = 0.149).

Conclusions

Activated mutation of kit constituted 90.7% genetic alteration of Taiwanese with advanced GIST and no PDGFRA mutation was detected. Imatinib induced a sustained objective response in more than half of Taiwan advanced GIST patients. ORR did not differ between patients whose GISTs had no mutation, kit exon 9, and 11 mutations.
Literature
1.
Lewis JJ, Brennan MF. Soft tissue sarcoma. Curr Prob Surg 1996; 33(10):817–72CrossRef
2.
Rossi CR, Mocellin S, Mencarelli R, et al. Gastrointestinal stromal tumors: from a surgical to a molecular approach. Int J Cancer 2003; 107:171PubMedCrossRef
3.
DeMatteo RP, Lewis JJ, Leung D, et al. Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann Surg 2000; 231:51PubMedCrossRef
4.
Kindblom LG, Remotti HE, Aldenborg F, et al. Gastrointestinal pacemaker cell tumor (GIPACT): Gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal. Am J Pathol 1998; 152:1259–69PubMed
5.
Sircar K, Hewlett BR, Huizinga JD, et al. Interstitial cells of Cajal as precursors of gastrointestinal stromal tumors. Am J Surg Pathol 1999; 23:377–89PubMedCrossRef
6.
Joensuu H, Roberts PJ, Sarlomo-Rikala M, et al. Effect of tyrosine kinase inhibitor DTI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med 2001; 344:1052–56PubMedCrossRef
7.
Demetri GD, von Mehren M, Blanke CD, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 2002; 347 (7):472–80PubMedCrossRef
8.
Yeh CN, Chen TW, Wu TJ, Jan YY, Chen MF. Treatment of patients with advanced gastrointestinal stromal tumor (GIST) of small bowel: Implications of imatinib mesylate. World J Gastroenterol 2006; 12(23):3760–5PubMed
9.
Akwari OE, Dozois RR, Weiland LH, Bearhrs OH. Leiomyosarcoma of the small and large bowel. Cancer 1978; 42:1375–84PubMedCrossRef
10.
Shiu MH, Farr GH, Papchristou DN, et al. Myosarcoma of the stomach: nature history, prognostic factors and management. Cancer 1982; 49:177–87PubMedCrossRef
11.
McGrath PC, Neifeld JP, Lawrence WJ, et al. Gastrointestinal sarcomas. Analysis of prognostic factors. Ann Surg 1987; 206:706–10PubMedCrossRef
12.
Ng EH, Pollock RE, Munsell MF, et al. Prognostic factors influencing survival in gastrointestinal leiomyosarcoma. Implications for surgical management and staging. Ann Surg 1992; 215:68–77PubMedCrossRef
13.
Druker BJ, Tamura S, Buchdunger E, et al. Effects of a selective inhibitor of the Abl tyrosin kinase on the growth of Bcr-Abl positive cells. Nat Med 1996; 2:561–6PubMedCrossRef
14.
Buchdunger E, Cioffi C, Law N, et al. Abl protein-tyrosine kinase inhibitor STI571 inhibits in vitro signal transduction mediated by c-kit and platelet-derived growth factor receptors. J Pharmacol Exp Ther2000; 295:139–45PubMed
15.
Heinrich MC, Griffith DJ, Druker BJ, et al. Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor. Blood 2000; 96:925–32PubMed
16.
Wang WL, Healy ME, Satter M, et al. Growth inhibition and modulation of kinase pathways of small cell lung cancer cell lines by the novel tyrosine kinase inhibitor STI 571. Oncogene 2000; 19:3521–8PubMedCrossRef
17.
Green S, Weiss GR Southwest Oncology Group standard response criteria, end point definitions and toxicity criteria. Invest New Drugs 1992; 10:239–53PubMedCrossRef
18.
Heinrich MC, Corless CL, Demetri GD, et al. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol 2003; 21(23):4342–49PubMedCrossRef
19.
Langer C, Gunawan B, Schuler P, Huber W, Fuzesi L, Becker H. Prognostic factors influencing surgical management and outcome of gastrointestinal stromal tumors. Br J Surg 2003; 90:332–9PubMedCrossRef
20.
Pierie JP, Choudry U, Muzikansky A, Yeap BY, Souba WW, Ott MJ. The effect of surgery and grade on outcome of gastrointestinal tumors. Arch Surg 2001; 136:383–9PubMedCrossRef
21.
Plaat BE, Hollema H, Molenaar WM, et al. Soft tissue leiomyosarcomas and malignant gastrointestinal stromal tumors: differences in clinical outcome and expression of multidrug resistant proteins. J Clin Oncol 2000; 18:3211–20PubMed
22.
Rankin C, von Mehren M, Blanke C, et al. Continued prologation of survival by imatinib in patients with metastatic GIST. Update of results from North American Intergroup phase III study S0033. Proc Am Soc Clin Oncol 2004; 23:815–84 (Abstr 9005)
23.
Zalcberg J. Proc Am Soc Clin Oncol 2004; 23:815. (Abstr 9004)
24.
Heinrich MC, Corless CL, Duensing A, et al. PDGFRA activating mutations in gastrointestinal tumors. Science 2003; 299:708–10PubMedCrossRef
25.
Miettinen M, Sarlomo-Rikala M, Lasota J. Gastrointestinal stromal tumors: recent advances in understanding of their biology. Hum Pathol 1999; 30:1213–1220PubMedCrossRef
Metadata
Title
Kinase Mutations and Imatinib Mesylate Response for 64 Taiwanese with Advanced GIST: Preliminary Experience from Chang Gung Memorial Hospital
Authors
Chun-Nan Yeh, MD
Tsung-Wen Chen, MD
Hsiang-Lin Lee, MD
Yu-Yin Liu, MD
Tzu-Chieh Chao, MD, PhD
Tsann-Long Hwang, MD, FACS
Yi-Yin Jan, MD, FACS
Miin-Fu Chen, MD, FACS
Publication date
01-03-2007
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 3/2007
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-006-9288-1

Other articles of this Issue 3/2007

Annals of Surgical Oncology 3/2007 Go to the issue

OriginalPaper

Distal Bile Duct Carcinoma: Prognostic Factors After Curative Surgery. A Series of 112 Cases

OriginalPaper

Results of MRI Screening for Breast Cancer in High-Risk Patients with LCIS and Atypical Hyperplasia

OriginalPaper

Resection of Isolated Pelvic Recurrences After Colorectal Surgery: Long-Term Results and Predictors of Improved Clinical Outcome

Gastrointestinal Oncology

Emergency Room Presentation of Colorectal Cancer: A Consecutive Cohort Study

OriginalPaper

Tumor Location of the Lower-Inner Quadrant Is Associated with an Impaired Survival for Women With Early-Stage Breast Cancer

EditorialNotes

Monitoring Health Outcomes Following Cytoreductive Surgery Plus Intraperitoneal Hyperthermic Chemotherapy for Peritoneal Carcinomatosis