The outcome and predictive factors of sunitinib therapy in advanced gastrointestinal stromal tumors (GIST) after imatinib failure - one institution study
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- 作者：Piotr Rutkowski (1)
El?bieta Bylina (1)
Anna Klimczak (1)
Tomasz ?witaj (1)
S?awomir Falkowski (1)
Jacek Kroc (2)
Iwona ?ugowska (1)
Magdalena Brzeskwiniewicz (3)
Wojciech Melerowicz (4)
Czes?aw Osuch (5)
Ewa Mierzejewska (6)
Kacper Wasielewski (3)
Agnieszka Wo?niak (7)
Urszula Grzesiakowska (8)
Zbigniew I Nowecki (9)
Janusz A Siedlecki (10)
Janusz Limon (3) - 关键词：Sunitinib ; Genotype ; GIST ; Prognosis ; Predictive factors ; Arterial hypertension
- 刊名：BMC Cancer
- 出版年：2012
- 出版时间：December 2012
- 年：2012
- 卷：12
- 期：1
- 全文大小：248KB
- 参考文献：1. Demetri GD, von Mehren M, Blanke CD, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, Heinrich MC, Tuveson DA, Singer S, Janicek M, Fletcher JA, Silverman SG, Silberman SL, Capdeville R, Kiese B, Peng B, Dimitrijevic S, Druker BJ, Corless C, Fletcher CD, Joensuu H: Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. / New Engl J Med 2002, 347:472-80. CrossRef
2. Verweij J, Casali PG, Zalcberg J, LeCesne A, Reichardt P, Blay JY, Issels R, van Oosterom A, Hogendoorn PC, Van Glabbeke M, Bertulli R, Judson I: Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. / Lancet 2004, 364:1127-134. CrossRef
3. Joensuu H: Gastrointestinal stromal tumor (GIST). / Ann Oncol 2006,17(Suppl 10):x280-x286. CrossRef
4. Rutkowski P, Debiec-Rychter M, Ruka W: Gastrointestinal stromal tumors: key to diagnosis and choice of therapy. / Mol Diagn Ther 2008,12(3):131-43.
5. Rutkowski P, Nowecki ZI, D?biec-Rychter M, Grzesiakowska U, Michej W, Wo?niak A, Siedlecki JA, Limon J, Jerzak vel Dobosz A, K?kol M, Osuch C, Ruka W: Predictive factors for long term effects of imatinib therapy in patients with inoperable/metastatic CD117(+) gastrointestinal stromal tumors (GISTs). / J Canc Res Clin Oncol 2007, 133:589-97. CrossRef
6. Abrams TJ, Lee LB, Murray LJ, Pryer NK, Cherrington JM: SU11248 inhibits KIT and platelet-derived growth factor receptor beta in preclinical models of human small cell lung cancer. / Mol Cancer Ther 2003, 2:471-78.
7. O'Farrell AM, Abrams TJ, Yuen HA, Ngai TJ, Louie SG, Yee KW, Wong LM, Hong W, Lee LB, Town A, Smolich BD, Manning WC, Murray LJ, Heinrich MC, Cherrington JM: SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. / Blood 2003, 101:3597-605. CrossRef
8. Murray LJ, Abrams TJ, Long KR, Ngai TJ, Olson LM, Hong W, Keast PK, Brassard JA, O'Farrell AM, Cherrington JM, Pryer NK: SU11248 inhibits tumor growth and CSF-1R-dependent osteolysis in an experimental breast cancer bone metastasis model. / Clin Exp Metastasis 2003, 20:757-66. CrossRef
9. Mendel DB, Laird AD, Xin X, Louie SG, Christensen JG, Li G, Schreck RE, Abrams TJ, Ngai TJ, Lee LB, Murray LJ, Carver J, Chan E, Moss KG, Haznedar JO, Sukbuntherng J, Blake RA, Sun L, Tang C, Miller T, Shirazian S, McMahon G, Cherrington JM: In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. / Clin Cancer Res 2003, 9:327-37.
10. Kim DW, Jo YS, Jung HS, Chung HK, Song JH, Park KC, Park SH, Hwang JH, Rha SY, Kweon GR, Lee SJ, Jo KW, Shong M: An orally administered multitarget tyrosine kinase inhibitor, SU11248, is a novel potent inhibitor of thyroid oncogenic RET/papillary thyroid cancer kinases. / J Clin Endocrinol Metab 2006, 91:4070-076. CrossRef
11. Maki RG, Fletcher JA, Heinrich MC, Morgan JA, George S, Desai J, Scheu K, Fletcher CD, Baum C, Demetri GD: Results from a continuation trial of SU11248 in patients (pts) with imatinib (IM)-resistant gastrointestinal stromal tumor (GIST). / J Clin Oncol 2005,23(16S):Abs 9011..
12. Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, McArthur G, Judson IR, Heinrich MC, Morgan JA, Desai J, Fletcher CD, George S, Bello CL, Huang X, Baum CM, Casali PG: Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: A randomised controlled trial. / Lancet 2006, 368:1329-338. CrossRef
13. George S, Blay JY, Casali PG, Le Cesne A, Morgan JA, Pokela J, Quigley MT, Tassell V, Baum CM, Demetri GD: Continuous daily dosing (CDD) of sunitinib malate (SU) compares favorably with intermittent dosing in pts with advanced GIST. / J Clin Oncol 2007,25(18S):Abs 10015..
14. Reichardt P, Kang YK, Ruka W, Seddon B, Baum CM, Demetri GD: Subpopulation analyses in a worldwide treatment-use trial of sunitinib (SU) in GIST patients (pts) with resistance or intolerance to prior imatinib (IM) therapy. / J Clin Oncol 2007,25(18S):Abs 10022..
15. Levy BI: Blood pressure as a potential biomarker of the efficacy angiogenesis inhibitor. / Ann Oncol 2009, 20:200-03. CrossRef
16. Rini BI, Cohen DP, Lu DR, Chen I, Hariharan S, Gore ME, Figlin RA, Baum MS, Motzer RJ: Hypertension as a Biomarker of Efficacy in Patients With Metastatic Renal Cell Carcinoma Treated With Sunitinib. / J Natl Cancer Inst 2011, 103:763-73. CrossRef
17. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG: New guidelines to evaluate the response to treatment in solid tumors. / J Natl Cancer Inst 2000, 92:205-16. CrossRef
18. Cancer therapy evaluation program: / Common terminology criteria for adverse events version 3.0 (CTCAE). Bethesda, MD: National Cancer Institute; 2003.
19. Wozniak A, Rutkowski P, Piskorz A, Ciwoniuk M, Osuch C, Bylina E, Sygut J, Chosia M, Rys J, Urbanczyk K, Kruszewski W, Sowa P, Siedlecki J, Debiec-Rychter M, Limon J, on behalf of Polish Clinical GIST Registry: Prognostic value of KIT/PDGFRA mutations in gastrointestinal stromal tumours (GIST): Polish Clinical GIST Registry experience. / Ann Oncol 2011, in press.
20. Blay J-Y: Pharmacological management of gastrointestinal stromal tumours: an update on the role of sunitinib. / Ann Oncol 2010, 21:208-15. CrossRef
21. Dudeck O, Zeile M, Reichardt P, Pink D: Comparison of RECIST and Choi criteria for computed tomographic response evaluation in patients with advanced gastrointestinal stromal tumor treated with sunitinib. / Ann Oncol 2011,22(8):1828-833. CrossRef
22. Yoon DH, Ryu M-H, Ryoo B-Y, Beck M, Choi D-R, Cho Y, Lee Y-L, Chang H-M, Kim TW, Kang Y-K: Sunitinib as a second-line therapy for advanced GISTs after failure of imatinib: relationship between efficacy and tumor genotype in Korean patients. / Invest New Drugs 2011. doi 10.1007/s10637-10-593- S2
23. Heinrich MC, Maki RG, Corless CL, Antonescu CR, Harlow A, Griffith D, Town A, McKinley A, Ou W-B, Fletcher JA, Fletcher CDM, Huang X, Cohen DP, Baum CM, Demetri GD: Primary and Secondary Kinase Genotypes Correlate With the Biological and Clinical Activity of Sunitinib in Imatinib-Resistant Gastrointestinal Stromal Tumor. / J Clin Oncol 2008, 26:5352-359. CrossRef
24. Demetri GD, Heinrich MC, Fletcher JA, Fletcher CDM, Van den Abbeele AD, Corless CL, Antonescu CR, George S, Morgan JA, Chen MH, Bello CL, Huang X, Cohen DP, Baum CM, Maki RG: Molecular target modulation, imaging, and clinical evaluation of gastrointestinal stromal tumor patients treated with sunitinib malate after imatinib failure. / Clin Cancer Res 2009,15(18):5902-909. CrossRef
25. Guo T, Hajdu M, Agaram NP, Shinoda H, Veach D, Clarkson BD, Maki RG, Singer S, Dematteo RP, Besmer P, Antonescu CR: Mechanisms of sunitinib resistance in gastrointestinal stromal tumors harboring KITAY502-ins mutation: an in vitro mutagenesis screen for drug resistance. / Clin Cancer Res 2009,15(22):6862-870. CrossRef
26. Nishida T, Takahashi T, Nishitani A, Doi T, Shirao K, Komatsu Y, Nakajima K, Hirota S: Sunitinib-resistant gastrointestinal stromal tumors harbor cis-mutations in the activation loop of the KIT gene. / Int J Clin Oncol 2009,14(2):143-49. CrossRef
27. DiNitto JP, Deshmukh GD, Zhang Y, Jacques SL, Coli R, Worrall JW, Diehl W, English JM, Wu JC: Function of activation loop tyrosine phosphorylation in the mechanism of c-Kit auto-activation and its implication in sunitinib resistance. / J Biochem 2010,147(4):601-09. CrossRef
28. Gajiwala KS, Wu JC, Christensen J, Deshmukh GD, Diehl W, DiNitto JP, English JM, Greig MJ, He YA, Jacques SL, Lunney EA, McTigue M, Molina D, Quenzer T, Wells PA, Yu X, Zhang Y, Zou A, Emmett MR, Marshall AG, Zhang HM, Demetri GD: KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients. / Proc Natl Acad Sci USA 2009,106(5):1542-547. CrossRef
29. Antonescu CR, Besmer P, Guo T, Arkun K, Hom G, Koryotowski B, Leversha MA, JeVrey PD, Desantis D, Singer S, Brennan MF, Maki RG, DeMatteo RP: Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation. / Clin Cancer Res 2005,11(11):4182-190. CrossRef
30. Wardelmann E, Merkelbach-Bruse S, Pauls K, Thomas N, Schildhaus HU, Heinicke T, Speidel N, Pietsch T, Buettner R, Pink D, Reichardt P, Hohenberger P: Polyclonal evolution of multiple secondary KIT mutations in gastrointestinal stromal tumors under treatment with imatinib mesylate. / Clin Cancer Res 2006,12(6):1743-749. CrossRef
31. Desai J, Yassa L, Marqusee E, George S, Frates MC, Chen MH, Morgan JA, Dychter SS, Larsen PR, Demetri GD, Alexander EK: Hypothyroidism after sunitinib treatment for patients with gastrointestinal stromal tumors. / Ann Intern Med 2006,145(9):660-64.
32. Wolter P, Stefan C, Decallonne B, Dumez H, Bex M, Carmeliet P, Schoeffski P: The clinical implications of sunitinib-induced hypothyroidism: a prospective evaluation. / Br J Cancer 2008, 99:448-54. CrossRef
33. Ruka W, Rutkowski P, Nowecki Z, Dziewirski W: Emergency surgery due to complications during molecular targeted therapy in advanced gastrointestinal stromal tumors (GIST). / Ann Surg Oncol 2008,15(Suppl 2):27. abstr 82
34. Rutkowski P, Ruka W: Emergency surgery in the era of molecular treatment of solid tumors. / Lancet Oncol 2009,10(2):157-63. CrossRef
35. Van Der Graaf WT, Blay JY, Chawla SP, Kim D, Nguyen BB, Casali PG, Sch?ffski P, Aglietta M, Staddon AP, Beppu Y, Le Cesne A, Gelderblom H, Judson IR, Araki N, Ouali M, Marreaud S, Hodge R, Dewji M, Dei Tos AP, Hohenberger P: PALETTE: A randomized, double-blind, phase III trial of pazopanib versus placebo in patients (pts) with soft-tissue sarcoma (STS) whose disease has progressed during or following prior chemotherapy-An EORTC STBSG Global Network Study (EORTC 62072). / J Clin Oncol 2011, (Suppl):29. abstr LBA10002
36. Zhu X, Stergiopoulos K, Wu S: Risk of hypertension and renal dysfunction with an angiogenesis inhibitor sunitinib: systematic review and meta-analysis. / Acta Oncol 2009,48(1):9-7. CrossRef
37. Ravaud A, Sire M: Arterial hypertension and clinical benefit of sunitinib, sorafenib and bevacizumab in first and second-line treatment of metastatic renal cell cancer. / Ann Oncol 2009, 20:966-67. CrossRef
38. Szmit S, Langiewicz P, Zo?nierek J, Nurzyński P, Zaborowska M, Filipiak KJ, Opolski G, Szczylik C: Hypertension as a predictive factor for survival outcomes in patients with metastatic renal cell carcinoma treated with sunitinib after progression on cytokines. / Kidney Blood Press Res 2011, in press.
39. Bono P, Rautiola J, Utriainen T, Joensuu H: Hypertension as predictor of sunitinib treatment outcome in metastatic renal cell carcinoma. / Acta Oncol 2011,50(4):569-3. Epub 2011 Jan 5 CrossRef
40. Hood JD, Meininger CJ, Ziche M, Granger HJ: VEGF upregulates ecNOS message, protein, and NO production in human endothelial cells. / Am J Physiol 1998,274(3, pt 2):H1054-H1058.
41. van der Veldt AA, de Boer MP, Boven E, Eringa EC, van der Eertwegh AJ, van Hinsbergh VW, Smudlers YM, Serne EH: Reduction in skin microvascular density and changes in vessel morphology in patients treated with sunitinib. / Anticancer Drugs 2010,21(4):439-46. CrossRef
42. Vaziri SA, Kim J, Ganapathi MK, Ganapathi R: Vascular endothelial growth factor polymorphisms: role in response and toxicity of tyrosine kinase inhibitors. / Curr Oncol Rep 2010, 12:102-08. CrossRef
43. Kim JJ, Vaziri SA, Rini BI, Elson P, Garcia JA, Wirka R, Dreicer R, Ganapathi MK, Ganapathi R: Association of VEGF and VEGFR2 single nucleotide polymorphisms with hypertension and clinical outcome in metastatic clear cell renal cell carcinoma patients treated with sunitinib. / Cancer 2011, in press. doi: 10.1002/cncr.26491
44. Schneider BP, Radovich M, Miller KD: The role of vascular endothelial growth factor genetic variability in cancer. / Clin Cancer Res 2009, 15:5297-302. CrossRef
45. Jain L, Vargo CA, Danesi R, Sissung TM, Price DK, Venzon D, Venitz J, Figg WD: The role of vascular endothelial growth factor SNPs as predictive and prognostic markers for major solid tumors. / Mol Cancer Ther 2009, 8:2496-508. CrossRef
46. Schneider BP, Wang M, Radovich M, Sledge GW, Badve S, Thor A, Flockhart DA, Hancock B, Davidson N, Gralow J, Dickler M, Perez EA, Cobleigh M, Shenkier T, Edgerton S, Miller KD, ECOG 2100: Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100. / J Clin Oncol 2008, 26:4672-678. CrossRef
47. Baffert F, Le T, Sennino B, Thurston G, Kuo CJ, Hu-Lowe D, McDonald DM: Cellular changes in normal blood capillaries undergoing regression after inhibition of VEGF signaling. / Am J Physiol Heart Circ Physiol 2006, 290:H547-H559. CrossRef
48. Kamba T, Tam BY, Hashizume H, Haskell A, Sennino B, Mancuso MR, Norberg SM, O'Brien SM, Davis RB, Gowen LC, Anderson KD, Thurston G, Joho S, Springer ML, Kuo CJ, McDonald DM: VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature. / Am J Physiol Heart Circ Physiol 2006, 290:H560-H576. CrossRef
49. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/12/107/prepub - 作者单位：Piotr Rutkowski (1)
El?bieta Bylina (1)
Anna Klimczak (1)
Tomasz ?witaj (1)
S?awomir Falkowski (1)
Jacek Kroc (2)
Iwona ?ugowska (1)
Magdalena Brzeskwiniewicz (3)
Wojciech Melerowicz (4)
Czes?aw Osuch (5)
Ewa Mierzejewska (6)
Kacper Wasielewski (3)
Agnieszka Wo?niak (7)
Urszula Grzesiakowska (8)
Zbigniew I Nowecki (9)
Janusz A Siedlecki (10)
Janusz Limon (3)
1. Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
2. Pfizer Poland, Warsaw, Poland
3. Department of Biology and Genetics, Medical University of Gdansk, Gdansk, Poland
4. GreaterPoland Oncological Center, Poznan, Poland
5. Department of General Surgery, Jagiellonian University, Medical Faculty, Cracow, Poland
6. Department of Biostatistics, Institute of Mother and Child, Warsaw, Poland
7. Laboratory of Experimental Oncology and Department of General Medical Oncology, KU Leuven and University Hospital, Leuven, Belgium
8. Department of Radiology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
9. Department of Gastrointestinal Tumors, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
10. Department of Molecular Biology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland - ISSN：1471-2407
文摘
Background Gastrointestinal stromal tumors (GIST) mutational status is recognized factor related to the results of tyrosine kinase inhibitors therapy such as imatinib (IM) or sunitinib (SU). Arterial hypertension (AH) is common adverse event related to SU, reported as predictive factor in renal cell carcinoma. The aim of the study was to analyze the outcomes and factors predicting results of SU therapy in inoperable/metastatic CD117(+) GIST patients after IM failure. Methods We identified 137 consecutive patients with advanced inoperable/metastatic GIST treated in one center with SU (2nd line treatment). Median follow-up time was 23 months. Additionally, in 39 patients there were analyzed selected constitutive single nucleotide polymorphisms (SNPs) of VEGFA and VEGFR2 genes. Results One year progression-free survival (PFS; calculated from the start of SU) rate was 42% and median PFS was 43 weeks. The estimated overall survival (OS, calculated both from start of SU or IM) was 74 weeks and 51 months, respectively. One-year PFS was 65% (median 74 weeks) in 55 patients with AH vs. 22% (median 17 weeks) in patients without AH. Patients with primary tumors carrying mutations in KIT exon 9 or wild-type had substantially better 1-year PFS (68% and 57%; median 65.5 and 50.5 weeks, respectively) than patients having tumors with KIT exon 11 or PDGFRA mutations (34% and 15%; median 36.8 and 9 weeks, respectively). We identified two independent factors with significant impact on PFS and OS in univariate and multivariate analysis: primary tumor genotype and presence of AH. The most common adverse events during therapy were: fatigue, AH, hypothyroidism, hand and foot syndrome, mucositis, skin reactions, dyspepsia, and diarrhea. Two deaths were assessed as related to tumor rupture caused by reaction to SU therapy. The presence of C-allele in rs833061 and the T-allele in rs3025039 polymorphism of VEGFA were associated with significantly higher risk of hypothyroidism (OR: 10.0 p = 0.041 and OR: 10.5; p = 0.015, respectively). Conclusions We confirmed that many advanced GIST patients benefit from SU therapy with OS > 1.5 year. Primary tumor KIT/PDGFRA genotype and SU-induced AH, as surrogate of its antiangiogenic activity are two independent factors influencing both PFS and OS. Note The preliminary data of this study were presented during Annual Meeting of American Society of Clinical Oncology, 4-8 June 2011 and Connective Tissue Oncology Society Meeting, 26-28 October 2011 in Chicago, IL.