Wybrane aspekty stosowania inhibitorów kinaz tyrozynowych w terapii chorych na nowotwory podścieliskowe przewodu pokarmowego Artykuł przeglądowy
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Opublikowane:
mar 30, 2012
Słowa kluczowe:
nowotwory podścieliskowe przewodu pokarmowego, GIST, inhibitory kinaz tyrozynowych, imatynib, sunitynib, ocena odpowiedzi na leczenie, długość trwania leczenia, dawkowanie, toksyczność
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Abstrakt
Nowotwory podścieliskowe przewodu pokarmowego (GIST, gastrointestinal stromal tumor) są najczęstszymi nowotworami złośliwymi pochodzenia mezenchymalnego przewodu pokarmowego. Najczęściej umiejscawiają się w żołądku i jelicie cienkim. W przeszłości nowotwory te mogły być klasyfikowane jako mięsaki gładkokomórkowe. W ostatnich latach leczenie GIST uległo znaczącej ewolucji. Historycznie leczenie chirurgiczne było jedyną efektywną metodą terapeutyczną, ponieważ nawrotowe i zaawansowane GIST charakteryzowały się opornością na klasyczną chemioterapię i radioterapię. W większości przypadków do rozwoju GIST dochodzi w wyniku wystąpienia mutacji w domenie kinazy tyrozynowej receptora KIT bądź PDGFRα. Wprowadzenie do praktyki klinicznej imatynibu – inhibitora KIT i PDGFRα – spowodowało fundamentalne zmiany nie tylko w leczeniu wczesnych i zaawansowanych GIST, ale także w myśleniu o terapii celowanej nowotworów złośliwych. Obecnie imatynib jest wskazany w terapii I linii uogólnionych GIST oraz w leczeniu uzupełniającym chorych na GIST z wysokim ryzykiem nawrotu choroby. Sunitynib jest obecnie jedynym lekiem zarejestrowanym w leczeniu uogólnionych GIST po niepowodzeniu terapii imatynibem lub w przypadku jego nietolerancji, jednak wiele leków – głównie inhibitorów kinaz tyrozynowych – jest poddawanych ocenie w kontrolowanych badaniach klinicznych. Jednakże ich wprowadzenie do praktyki klinicznej wywołało także dyskusje i kontrowersje związane z oceną odpowiedzi na leczenie, długością trwania leczenia i właściwym dawkowaniem. Niektóre z tych aspektów stosowania inhibitorów kinaz tyrozynowych w leczeniu GIST i historia wprowadzenia tej grupy do praktyki klinicznej zostały przedstawione w naszej pracy.
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Czartoryska-Arłukowicz B, Tokajuk P, Wojtukiewicz MZ. Wybrane aspekty stosowania inhibitorów kinaz tyrozynowych w terapii chorych na nowotwory podścieliskowe przewodu pokarmowego. OncoReview [Internet]. 30 marzec 2012 [cytowane 4 grudzień 2024];2(1(5):8-18. Dostępne na: https://journalsmededu.pl/index.php/OncoReview/article/view/289
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Copyright: © Medical Education sp. z o.o. This is an Open Access article distributed under the terms of the Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). License (https://creativecommons.org/licenses/by-nc/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
Address reprint requests to: Medical Education, Marcin Kuźma (marcin.kuzma@mededu.pl)
Bibliografia
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21. Zalcberg J.R., Verweij J., Casali P.G. et al.: Outcome of patients with advanced gastrointestinal stromal tumours crossing over to a daily imatinib dose of 800 mg after progression on 400 mg. Eur. J. Cancer 2005; 41: 1751-1757.
22. Heinrich M.C.: Imatinib treatment of metastatic GIST: don’t stop (believing). Lancet Oncol. 2010; 11: 910-911.
23. Le Cesne A., Ray-Coquard I., Bui B.N. et al.: Discontinuation of imatinib in patients with advanced gastrointestinal stromal tumours after 3 years of treatment: an open-label multicentre randomised phase 3 trial. Lancet Oncol. 2010; 11: 942-949.
24. Rutkowski P., Kulig J., Krzakowski M. et al.: Zasady postępowania diagnostyczno-terapeutycznego u chorych na nowotwory podścieliskowe przewodu pokarmowego (GIST) w 2010 roku. Onkologia w Praktyce Klinicznej 2010; 6: 181-194.
25. Gastrointestinal Stromal Tumor Meta-Analysis Group (MetaGIST). Comparison of Two Doses of Imatinib for the Treatment of Unresectable or Metastatic Gastrointestinal Stromal Tumors: A Meta-Analysis of 1,640 Patients. J. Clin. Oncol. 2010; 28: 1247-1253.
26. Heinrich M.C., Rubin B.P., Longley B.J., Fletcher J.A.: Biology and genetic aspects of gastrointestinal stromal tumors: KIT activation and cytogenetic alterations. Hum. Pathol. 2002; 33: 484-495.
27. Corless C.L.: Assessing the prognosis of gastrointestinal stromal tumors: a growing role for molecular testing. Am. J. Clin. Pathol. 2004; 122: 11-13.
28. Heinrich M.C., Corless C.L., Demetri G.D. et al.: Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J. Clin. Oncol. 2003; 21: 4342-4349.
29. Corless C.L., Schroeder A., Griffith D. et al.: PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib. J. Clin. Oncol. 2005; 23: 5357-5364.
30. Debiec-Rychter M., Sciot R., Le Cesne A. et al.: KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. Eur. J. Cancer 2006; 42: 1093-1103.
31. Casali P.G., Blay J.Y.: Gastrointestinal stromal tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2008; 21(Suppl. 5): v98-102.
32. Casali P.G., Blay J.Y. on behalf of the ECECPoE. Gastrointestinal stromal tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2010; 21: v98-v102.
33. Demetri G.D., Wang Y., Wehrle E. et al.: Imatinib plasma levels are correlated with clinical benefit in patients with unresectable/metastatic gastrointestinal stromal tumors. J. Clin. Oncol. 2009; 27: 3141-3147.
34. Joensuu H., Trent J.C., Reichardt P.: Practical management of tyrosine kinase inhibitor-associated side effects in GIST. Cancer Treat. Rev. 2011 Feb; 37(1): 75-88.
35. Harrison M.L., Goldstein D.: Management of metastatic gastrointestinal stromal tumour in the Glivec era: a practical case-based approach. Internal Medicine Journal 2006; 36: 367-377.
36. Therasse P., Arbuck S.G., Eisenhauer E.A. et al.: New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J. Natl. Cancer Inst. 2000; 92: 205-216.
37. Shankar S., van Sonnenberg E., Desai J. et al.: Gastrointestinal stromal tumor: new nodule-within-a-mass pattern of recurrence after partial response to imatinib mesylate. Radiology 2005; 235: 892-898.
38. Choi H., Charnsangavej C., Faria S.C. et al.: Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: proposal of new computed tomography response criteria. J. Clin. Oncol. 2007; 25: 1753-1759.
39. Holdsworth C.H., Badawi R.D., Manola J.B. et al.: CT and PET: Early Prognostic Indicators of Response to Imatinib Mesylate in Patients with Gastrointestinal Stromal Tumor. Am. J. Roentgenol. 2007; 189: W324-330.
40. van den Abbeele A.D.: The Lessons of GIST - PET and PET/CT: A New Paradigm for Imaging. Oncologist 2008; 13: 8-13.
41. Prior J.O., Montemurro M., Orcurto M.V. et al.: Early Prediction of Response to Sunitinib After Imatinib Failure by 18F-Fluorodeoxyglucose Positron Emission Tomography in Patients With Gastrointestinal Stromal Tumor. J. Clin. Oncol. 2009; 27: 439-445.
42. Stroobants S., Goeminne J., Seegers M. et al.: 18FDG-Positron emission tomography for the early prediction of response in advanced soft tissue sarcoma treated with imatinib mesylate (Glivec). Eur. J. Cancer 2003; 39: 2012-2020.
43. Choi H., Charnsangavej C., Faria S.C. et al.: CT Evaluation of the Response of Gastrointestinal Stromal Tumors After Imatinib Mesylate Treatment: A Quantitative Analysis Correlated with FDG PET Findings. Am. J. Roentgenol. 2004; 183: 1619-1628.
44. Judson I., Ma P., Peng B. et al.: Imatinib pharmacokinetics in patients with gastrointestinal stromal tumour: a retrospective population pharmacokinetic study over time. EORTC Soft Tissue and Bone Sarcoma Group. Cancer Chemother. Pharmacol. 2005; 55: 379-386.
45. Heinrich M.C., Maki R.G., Corless C.L. et al.: Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor. J. Clin. Oncol. 2008; 26: 5352-5359.
46. Antonescu C.R., Besmer P., Guo T. et al.: Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation. Clin. Cancer Res. 2005; 11: 4182-4190.
47. Raut C.P., Posner M., Desai J. et al.: Surgical management of advanced gastrointestinal stromal tumors after treatment with targeted systemic therapy using kinase inhibitors. J. Clin. Oncol. 2006; 24: 2325-2331.
48. Prenen H., Cools J., Mentens N. et al.: Efficacy of the kinase inhibitor SU11248 against gastrointestinal stromal tumor mutants refractory to imatinib mesylate. Clin. Cancer Res. 2006; 12: 2622-2627.
49. Demetri G.D., van Oosterom A.T., Garrett C.R. et al.: Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 2006; 368: 1329-1338.
50. George S., Blay J.Y., Casali P.G. et al.: Clinical evaluation of continuous daily dosing of sunitinib malate in patients with advanced gastrointestinal stromal tumour after imatinib failure. Eur. J. Cancer 2009; 45: 1959-1968.
51. DeMatteo R.P., Lewis J.J., Leung D. et al.: Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann. Surg. 2000; 231: 51-58.
52. Eisenberg B.L., Judson I.: Surgery and imatinib in the management of GIST: emerging approaches to adjuvant and neoadjuvant therapy. Ann. Surg. Oncol. 2004; 11: 465-475.
53. Dematteo R.P., Ballman K.V., Antonescu C.R. et al.: Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet 2009; 373: 1097-1104.
54. Corless C.L., Ballman K.V., Antonescu C. et al.: Relation of tumor pathologic and molecular features to outcome after surgical resection of localized primary gastrointestinal stromal tumor (GIST): Results of the intergroup phase III trial ACOSOG Z9001. ASCO Meeting Abstracts 2010; 28: 10006.
55. Blesius A., Cassier P.A., Bertucci F. et al.: Neoadjuvant imatinib in patients with locally advanced non metastatic GIST in the prospective BFR14 trial. BMC Cancer 2011; 11: 72.
56. Eisenberg B.L., Smith K.D.: Adjuvant and neoadjuvant therapy for primary GIST. Cancer Chemother. Pharmacol. 2011; 67(Suppl. 1): S3-8.
57. Reynoso D., Trent J.C.: Neoadjuvant and adjuvant imatinib treatment in gastrointestinal stromal tumor: current status and recent developments. Curr. Opin. Oncol. 2010; 22: 330-335.
58. DeMatteo R.P., Maki R.G., Singer S. et al.: Results of tyrosine kinase inhibitor therapy followed by surgical resection for metastatic gastrointestinal stromal tumor. Ann. Surg. 2007; 245: 347-352.
59. Rutkowski P., Nowecki Z., Nyckowski P. et al.: Surgical treatment of patients with initially inoperable and/or metastatic gastrointestinal stromal tumors (GIST) during therapy with imatinib mesylate. J. Surg. Oncol. 2006; 93: 304-311.
60. Ruka W., Rutkowski P., Szawlowski A. et al.: Surgical resection of residual disease in initially inoperable imatinib-resistant/intolerant gastrointestinal stromal tumor treated with sunitinib. Eur. J. Surg. Oncol. 2009; 35: 87-91.
61. Eisenberg B.L., Harris J., Blanke C.D. et al.: Phase II trial of neoadjuvant/adjuvant imatinib mesylate (IM) for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumor (GIST): early results of RTOG 0132/ACRIN 6665. J. Surg. Oncol. 2009; 99: 42-47.
2. Plager C., Papadopoulos N.E., Salem P. et al.: Adriamycin based chemotherapy for leiomyosarcoma of the stomach and small bowel. Proc. Am. Soc. Clin. Oncol. 1991; 10: 352 (A1251).
3. Patel S.R., Legha S.S., Salem P.A. et al.: Evaluation of ifosfamide in metastatic leiomyosarcoma of gastrointestinal origin. Proc. Am. Soc. Clin. Oncol. 1991; 10: 352 (abstr. 1252).
4. Edmonson J.H., Marks R.S., Buckner J.C., Mahoney M.R.: Contrast of response to dacarbazine, mitomycin, doxorubicin, and cisplatin (DMAP) plus GM-CSF between patients with advanced malignant gastrointestinal stromal tumors and patients with other advanced leiomyosarcomas. Cancer Invest. 2002; 20: 605-612.
5. Heinrich M.C., Blanke C.D., Druker B.J., Corless C.L.: Inhibition of KIT tyrosine kinase activity: a novel molecular approach to the treatment of KIT-positive malignancies. J. Clin. Oncol. 2002; 20: 1692-1703.
6. Tuveson D.A., Willis N.A., Jacks T. et al.: STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: biological and clinical implications. Oncogene 2001; 20: 5054-5058.
7. Croom K.F., Perry C.M.: Imatinib mesylate: in the treatment of gastrointestinal stromal tumours. Drugs 2003; 63: 513-522.
8. Heinrich M.C., Corless C.L.: Targeting mutant kinases in gastrointestinal stromal tumors: a paradigm for molecular therapy of other sarcomas. Cancer Treat. Res. 2004; 120: 129-150.
9. Heinrich M.C., Griffith D.J., Druker B.J. et al.: Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor. Blood 2000; 96: 925-932.
10. Miettinen M., Lasota J.: Gastrointestinal stromal tumors: review on morphology, molecular pathology, prognosis, and differential diagnosis. Arch. Pathol. Lab. Med. 2006; 130: 1466-1478.
11. Corless C.L., Heinrich M.C.: Molecular pathobiology of gastrointestinal stromal sarcomas. Annu. Rev. Pathol. 2008; 3: 557-586.
12. Heinrich M.C., Corless C.L., Duensing A. et al.: PDGFRA activating mutations in gastrointestinal stromal tumors. Science 2003; 299: 708-710.
13. Corless C.L., Fletcher J.A., Heinrich M.C.: Biology of gastrointestinal stromal tumors. J. Clin. Oncol. 2004; 22: 3813-3825.
14. Trent J.C., Benjamin R.S.: New developments in gastrointestinal stromal tumor. Curr. Opin. Oncol. 2006; 18: 386-395.
15. Joensuu H., Roberts P.J., Sarlomo-Rikala M. et al.: Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N. Engl. J. Med. 2001; 344: 1052-1056.
16. van Oosterom A.T., Judson I., Verweij J. et al.: Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study. Lancet 2001; 358: 1421-1423.
17. Demetri G.D., von Mehren M., Blanke C.D. et al.: Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N. Engl. J. Med. 2002; 347: 472-480.
18. Blanke C.D., Demetri G.D., von Mehren M. et al.: Long-term results from a randomized phase II trial of standard- versus higher-dose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT. J. Clin. Oncol. 2008; 26: 620-625.
19. Verweij J., Casali P.G., Zalcberg J. et al.: Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet 2004; 364: 1127-1134.
20. Blanke C.D., Rankin C., Demetri G.D. et al.: Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033. J. Clin. Oncol. 2008; 26: 626-632.
21. Zalcberg J.R., Verweij J., Casali P.G. et al.: Outcome of patients with advanced gastrointestinal stromal tumours crossing over to a daily imatinib dose of 800 mg after progression on 400 mg. Eur. J. Cancer 2005; 41: 1751-1757.
22. Heinrich M.C.: Imatinib treatment of metastatic GIST: don’t stop (believing). Lancet Oncol. 2010; 11: 910-911.
23. Le Cesne A., Ray-Coquard I., Bui B.N. et al.: Discontinuation of imatinib in patients with advanced gastrointestinal stromal tumours after 3 years of treatment: an open-label multicentre randomised phase 3 trial. Lancet Oncol. 2010; 11: 942-949.
24. Rutkowski P., Kulig J., Krzakowski M. et al.: Zasady postępowania diagnostyczno-terapeutycznego u chorych na nowotwory podścieliskowe przewodu pokarmowego (GIST) w 2010 roku. Onkologia w Praktyce Klinicznej 2010; 6: 181-194.
25. Gastrointestinal Stromal Tumor Meta-Analysis Group (MetaGIST). Comparison of Two Doses of Imatinib for the Treatment of Unresectable or Metastatic Gastrointestinal Stromal Tumors: A Meta-Analysis of 1,640 Patients. J. Clin. Oncol. 2010; 28: 1247-1253.
26. Heinrich M.C., Rubin B.P., Longley B.J., Fletcher J.A.: Biology and genetic aspects of gastrointestinal stromal tumors: KIT activation and cytogenetic alterations. Hum. Pathol. 2002; 33: 484-495.
27. Corless C.L.: Assessing the prognosis of gastrointestinal stromal tumors: a growing role for molecular testing. Am. J. Clin. Pathol. 2004; 122: 11-13.
28. Heinrich M.C., Corless C.L., Demetri G.D. et al.: Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J. Clin. Oncol. 2003; 21: 4342-4349.
29. Corless C.L., Schroeder A., Griffith D. et al.: PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib. J. Clin. Oncol. 2005; 23: 5357-5364.
30. Debiec-Rychter M., Sciot R., Le Cesne A. et al.: KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. Eur. J. Cancer 2006; 42: 1093-1103.
31. Casali P.G., Blay J.Y.: Gastrointestinal stromal tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2008; 21(Suppl. 5): v98-102.
32. Casali P.G., Blay J.Y. on behalf of the ECECPoE. Gastrointestinal stromal tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2010; 21: v98-v102.
33. Demetri G.D., Wang Y., Wehrle E. et al.: Imatinib plasma levels are correlated with clinical benefit in patients with unresectable/metastatic gastrointestinal stromal tumors. J. Clin. Oncol. 2009; 27: 3141-3147.
34. Joensuu H., Trent J.C., Reichardt P.: Practical management of tyrosine kinase inhibitor-associated side effects in GIST. Cancer Treat. Rev. 2011 Feb; 37(1): 75-88.
35. Harrison M.L., Goldstein D.: Management of metastatic gastrointestinal stromal tumour in the Glivec era: a practical case-based approach. Internal Medicine Journal 2006; 36: 367-377.
36. Therasse P., Arbuck S.G., Eisenhauer E.A. et al.: New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J. Natl. Cancer Inst. 2000; 92: 205-216.
37. Shankar S., van Sonnenberg E., Desai J. et al.: Gastrointestinal stromal tumor: new nodule-within-a-mass pattern of recurrence after partial response to imatinib mesylate. Radiology 2005; 235: 892-898.
38. Choi H., Charnsangavej C., Faria S.C. et al.: Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: proposal of new computed tomography response criteria. J. Clin. Oncol. 2007; 25: 1753-1759.
39. Holdsworth C.H., Badawi R.D., Manola J.B. et al.: CT and PET: Early Prognostic Indicators of Response to Imatinib Mesylate in Patients with Gastrointestinal Stromal Tumor. Am. J. Roentgenol. 2007; 189: W324-330.
40. van den Abbeele A.D.: The Lessons of GIST - PET and PET/CT: A New Paradigm for Imaging. Oncologist 2008; 13: 8-13.
41. Prior J.O., Montemurro M., Orcurto M.V. et al.: Early Prediction of Response to Sunitinib After Imatinib Failure by 18F-Fluorodeoxyglucose Positron Emission Tomography in Patients With Gastrointestinal Stromal Tumor. J. Clin. Oncol. 2009; 27: 439-445.
42. Stroobants S., Goeminne J., Seegers M. et al.: 18FDG-Positron emission tomography for the early prediction of response in advanced soft tissue sarcoma treated with imatinib mesylate (Glivec). Eur. J. Cancer 2003; 39: 2012-2020.
43. Choi H., Charnsangavej C., Faria S.C. et al.: CT Evaluation of the Response of Gastrointestinal Stromal Tumors After Imatinib Mesylate Treatment: A Quantitative Analysis Correlated with FDG PET Findings. Am. J. Roentgenol. 2004; 183: 1619-1628.
44. Judson I., Ma P., Peng B. et al.: Imatinib pharmacokinetics in patients with gastrointestinal stromal tumour: a retrospective population pharmacokinetic study over time. EORTC Soft Tissue and Bone Sarcoma Group. Cancer Chemother. Pharmacol. 2005; 55: 379-386.
45. Heinrich M.C., Maki R.G., Corless C.L. et al.: Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor. J. Clin. Oncol. 2008; 26: 5352-5359.
46. Antonescu C.R., Besmer P., Guo T. et al.: Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation. Clin. Cancer Res. 2005; 11: 4182-4190.
47. Raut C.P., Posner M., Desai J. et al.: Surgical management of advanced gastrointestinal stromal tumors after treatment with targeted systemic therapy using kinase inhibitors. J. Clin. Oncol. 2006; 24: 2325-2331.
48. Prenen H., Cools J., Mentens N. et al.: Efficacy of the kinase inhibitor SU11248 against gastrointestinal stromal tumor mutants refractory to imatinib mesylate. Clin. Cancer Res. 2006; 12: 2622-2627.
49. Demetri G.D., van Oosterom A.T., Garrett C.R. et al.: Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 2006; 368: 1329-1338.
50. George S., Blay J.Y., Casali P.G. et al.: Clinical evaluation of continuous daily dosing of sunitinib malate in patients with advanced gastrointestinal stromal tumour after imatinib failure. Eur. J. Cancer 2009; 45: 1959-1968.
51. DeMatteo R.P., Lewis J.J., Leung D. et al.: Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann. Surg. 2000; 231: 51-58.
52. Eisenberg B.L., Judson I.: Surgery and imatinib in the management of GIST: emerging approaches to adjuvant and neoadjuvant therapy. Ann. Surg. Oncol. 2004; 11: 465-475.
53. Dematteo R.P., Ballman K.V., Antonescu C.R. et al.: Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet 2009; 373: 1097-1104.
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