Efficacy of sorafenib in patients with gastrointestinal stromal tumors in the third‑ or fourth‑line treatment: A retrospective multicenter experience

Kefeli,Umut; Benekli,Mustafa; Sevinc,Alper; Yildiz,Ramazan; Kaplan,Muhammed   Ali; Ciltas,Aydin; Balakan,Ozan; Isikdogan,Abdurrahman; Coskun,Ugur; Dane,Faysal; Harputluoglu,Hakan; Karaca,Halit; Yazilitas,Dogan; Durnali,Ayse; Kaya,Ali  Osman; Demirci,Umut; Gumus,Mahmut; Buyukberber,Suleyman

doi:10.3892/ol.2013.1408

Efficacy of sorafenib in patients with gastrointestinal stromal tumors in the third‑ or fourth‑line treatment: A retrospective multicenter experience

Authors:
- Umut Kefeli
- Mustafa Benekli
- Alper Sevinc
- Ramazan Yildiz
- Muhammed Ali Kaplan
- Aydin Ciltas
- Ozan Balakan
- Abdurrahman Isikdogan
- Ugur Coskun
- Faysal Dane
- Hakan Harputluoglu
- Halit Karaca
- Dogan Yazilitas
- Ayse Durnali
- Ali Osman Kaya
- Umut Demirci
- Mahmut Gumus
- Suleyman Buyukberber
View Affiliations

Affiliations: Department of Medical Oncology, Medeniyet University Goztepe Training and Research Hospital, Istanbul, Turkey, Department of Medical Oncology, Gazi University Faculty of Medicine, Ankara, Turkey, Department of Medical Oncology, Gaziantep University Faculty of Medicine, Gaziantep, Turkey, Department of Medical Oncology, Dr. Lutfi Kirdar Kartal Education and Research Hospital, Istanbul, Turkey, Department of Medical Oncology, Dicle University Faculty of Medicine, Diyarbakir, Turkey, Department of Medical Oncology, Marmara University Faculty of Medicine, Istanbul, Turkey, Department of Medical Oncology, Inonu University Faculty of Medicine, Malatya, Turkey, Department of Medical Oncology, Erciyes University Faculty of Medicine, Kayseri, Turkey, Department of Medical Oncology, Konya Education and Research Hospital, Konya, Turkey, Department of Medical Oncology, Dr. A.Y. Ankara Oncology Education and Research Hospital, Ankara, Turkey, Department of Medical Oncology, Medicana Bahcelievler Hospital, Istanbul, Turkey, Department of Medical Oncology, Ataturk Education and Research Hospital, Ankara, Turkey
Published online on: June 17, 2013 https://doi.org/10.3892/ol.2013.1408
Pages: 605-611

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Sorafenib is a multi‑targeted tyrosine kinase receptor inhibitor used to treat patients with advanced gastrointestinal stromal tumors (GISTs). The present study evaluated the efficacy and tolerability of sorafenib therapy for patients with GISTs. Between January 2001 and November 2012, 25 patients, from multiple centers, who had received sorafenib as the third‑ or fourth‑line treatment for GISTs were investigated retrospectively. In total, 17 patients were male and eight were female. The median age was 54.0 years (range, 16‑82 years). From the patients, 21 received imatinib for longer than six months and four received it for less than six months. The clinical benefit rate of sorafenib was 40.0%. Treatment‑related adverse events were reported in 72% of patients. These adverse events were generally mild to moderate in intensity. The median progression‑free survival (PFS) and overall survival (OS) times of the patients who received sorafenib were 7.2 and 15.2 months, respectively. The duration of imatinib usage was an independent prognostic factor for PFS and OS. Sorafenib is an effective treatment in patients with GISTs showing a clinical benefit rate of 40.0% and an acceptable tolerability.

View Figures

View References

1.	Rubin BP, Heinrich MC and Corless CL: Gastrointestinal stromal tumour. Lancet. 369:1731–1741. 2007. View Article : Google Scholar : PubMed/NCBI
2.	Miettinen M and Lasota J: Gastrointestinal stromal tumors: review on morphology, molecular pathology, prognosis, and differential diagnosis. Arch Pathol Lab Med. 130:1466–1478. 2006.PubMed/NCBI
3.	Hirota S, Isozaki K, Moriyama Y, et al: Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. 279:577–580. 1998. View Article : Google Scholar : PubMed/NCBI
4.	Heinrich MC, Corless CL, Demetri GD, et al: Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol. 21:4342–4349. 2003. View Article : Google Scholar : PubMed/NCBI
5.	Heinrich MC, Corless CL, Duensing A, et al: PDGFRA activating mutations in gastrointestinal stromal tumors. Science. 299:708–710. 2003. View Article : Google Scholar : PubMed/NCBI
6.	Tran T, Davila JA and El-Serag HB: The epidemiology of malignant gastrointestinal stromal tumors: an analysis of 1,458 cases from 1992 to 2000. Am J Gastroenterol. 100:162–168. 2005. View Article : Google Scholar : PubMed/NCBI
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. 347:472–480. 2002. View Article : Google Scholar : PubMed/NCBI
8.	Akwari OE, Dozois RR, Weiland LH and Beahrs OH: Leiomyosarcoma of the small and large bowel. Cancer. 42:1375–1384. 1978. View Article : Google Scholar : PubMed/NCBI
9.	Shiu MH, Farr GH, Papachristou DN and Hajdu SI: Myosarcomas of the stomach: natural history, prognostic factors and management. Cancer. 49:177–187. 1982. View Article : Google Scholar : PubMed/NCBI
10.	McGrath PC, Neifeld JP, Lawrence W Jr, Kay S, Horsley JS 3rd and Parker GA: Gastrointestinal sarcomas. Analysis of prognostic factors. Ann Surg. 206:706–710. 1987. View Article : Google Scholar : PubMed/NCBI
11.	Ng EH, Pollock RE, Munsell MF, Atkinson EN and Romsdahl MM: Prognostic factors influencing survival in gastrointestinal leiomyosarcomas. Implications for surgical management and staging. Ann Surg. 215:68–77. 1992. View Article : Google Scholar
12.	Druker BJ, Tamura S, Buchdunger E, et al: Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med. 2:561–566. 1996. View Article : Google Scholar : PubMed/NCBI
13.	Buchdunger E, Cioffi CL, 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 Ther. 295:139–145. 2000.
14.	Heinrich MC, Griffith DJ, Druker BJ, Wait CL, Ott KA and Zigler AJ: Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor. Blood. 96:925–932. 2000.PubMed/NCBI
15.	Wang WL, Healy ME, Sattler 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. 19:3521–3528. 2000. View Article : Google Scholar : PubMed/NCBI
16.	Yeh CN, Chen TW, Wu TJ, Hsueh S and Jan YY: Treatment of patients with advanced gastrointestinal stromal tumor of small bowel: implications of imatinib mesylate. World J Gastroenterol. 12:3760–3765. 2006.PubMed/NCBI
17.	Yeh CN, Chen TW, Lee HL, et al: Kinase mutations and imatinib mesylate response for 64 Taiwanese with advanced GIST: preliminary experience from Chang Gung Memorial Hospital. Ann Surg Oncol. 14:1123–1128. 2007. View Article : Google Scholar : PubMed/NCBI
18.	Chen YY, Yeh CN, Cheng CT, et al: Sunitinib for Taiwanese patients with gastrointestinal stromal tumor after imatinib treatment failure or intolerance. World J Gastroenterol. 17:2113–2119. 2011. View Article : Google Scholar : PubMed/NCBI
19.	Rutkowski P, Debiec-Rychter M and Ruka W: Gastrointestinal stromal tumors: key to diagnosis and choice of therapy. Mol Diagn Ther. 12:131–143. 2008. View Article : Google Scholar : PubMed/NCBI
20.	Osusky KL, Hallahan DE, Fu A, et al: The receptor tyrosine kinase inhibitor SU11248 impedes endothelial cell migration, tubule formation, and blood vessel formation in vivo, but has little effect on existing tumor vessels. Angiogenesis. 7:225–233. 2004. View Article : Google Scholar
21.	Abrams TJ, Lee LB, Murray LJ, Pryer NK and Cherrington JM: SU11248 inhibits KIT and platelet-derived growth factor receptor beta in preclinical models of human small cell lung cancer. Mol Cancer Ther. 2:471–478. 2003.PubMed/NCBI
22.	Mendel DB, Laird AD, Xin X, et al: 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. 9:327–337. 2003.
23.	Murray LJ, Abrams TJ, Long KR, et al: SU11248 inhibits tumor growth and CSF-1R-dependent osteolysis in an experimental breast cancer bone metastasis model. Clin Exp Metastasis. 20:757–766. 2003. View Article : Google Scholar : PubMed/NCBI
24.	O’Farrell AM, Abrams TJ, Yuen HA, et al: SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood. 101:3597–3605. 2003.PubMed/NCBI
25.	Schueneman AJ, Himmelfarb E, Geng L, et al: SU11248 maintenance therapy prevents tumor regrowth after fractionated irradiation of murine tumor models. Cancer Res. 63:4009–4016. 2003.PubMed/NCBI
26.	Heinrich MC, Marino-Enriquez A, Presnell A, et al: Sorafenib inhibits many kinase mutations associated with drug-resistant gastrointestinal stromal tumors. Mol Cancer Ther. 11:1770–1780. 2012. View Article : Google Scholar : PubMed/NCBI
27.	Kindler HL, Campbell NP, Wroblewski K, et al: Sorafenib (SOR) in patients (pts) with imatinib (IM) and sunitinib (SU)-resistant (RES) gastrointestinal stromal tumors (GIST): Final results of a University of Chicago Phase II Consortium trial. J Clin Oncol (ASCO Meeting Proceedings). 29:100092011.
28.	Reichardt P, Montemurro M, Gelderblom H, et al: Sorafenib fourth-line treatment in imatinib-, sunitinib-, and nilotinib-resistant metastatic GIST: A retrospective analysis. J Clin Oncol (2009 ASCO Annual Meeting). 27(15 Suppl): Abstract 10564,. 2009.
29.	National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Soft Tissue Sarcoma. Version 2. 2012.www.NCCN.orghttps://www.NCCN.org. Accessed June 17, 2012.
30.	Eisenhauer EA, Therasse P, Bogaerts J, et al: New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 45:228–247. 2009. View Article : Google Scholar
31.	Miettinen M and Lasota J: Gastrointestinal stromal tumors - definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Arch. 438:1–12. 2001. View Article : Google Scholar
32.	Fletcher CD, Berman JJ, Corless C, et al: Diagnosis of gastrointestinal stromal tumors: A consensus approach. Hum Pathol. 33:459–465. 2002. View Article : Google Scholar : PubMed/NCBI
33.	Verweij J, Casali PG, Zalcberg J, et al: Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet. 364:1127–1134. 2004. View Article : Google Scholar : PubMed/NCBI
34.	Italiano A, Cioffi A, Coco P, et al: Patterns of care, prognosis, and survival in patients with metastatic gastrointestinal stromal tumors (GIST) refractory to first-line imatinib and second-line sunitinib. Ann Surg Oncol. 19:1551–1559. 2012. View Article : Google Scholar : PubMed/NCBI
35.	Miettinen M, El-Rifai W, Sobin LH and Lasota J: Evaluation of malignancy and prognosis of gastrointestinal stromal tumors: a review. Hum Pathol. 33:478–483. 2002. View Article : Google Scholar : PubMed/NCBI
36.	Nilsson B, Bümming P, Meis-Kindblom JM, et al: Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era - a population-based study in western Sweden. Cancer. 103:821–829. 2005. View Article : Google Scholar
37.	Cao H, Zhang Y, Wang M, et al: Prognostic analysis of patients with gastrointestinal stromal tumors: a single unit experience with surgical treatment of primary disease. Chin Med J (Engl). 123:131–136. 2010.PubMed/NCBI
38.	Keohan M, D’Adamo D, Qin L, et al: Analysis of toxicity in a phase II study of sorafenib in soft tissue sarcoma (STS). J Clin Oncol 2007 ASCO Annual Meeting Proceedings (Post-Meeting Edition). 25(18 Suppl): 100612007.