Abstract
Sunitinib is an oral multitargeted tyrosine kinase inhibitor of VEGF receptors and PDGF receptors and is approved for the treatments of advanced renal cell carcinoma and gastrointestinal stromal tumors. However, only few studies were conducted to investigate the effectiveness of the use of sunitinib in NSCLC. This study evaluated the clinical activity and tolerability of sunitinib in previously treated advanced NSCLC in Asian population, which, to our knowledge, has not previously been studied. We conducted an open-label, non-randomized phase II trial for Asian patients with advanced NSCLC. Patients 18 years of age or older had histologically proven stage IIIB or IV NSCLC which had progressed during or after treatment with at least one platinum-based combination chemotherapy regimen were included in this study. In all, 22 patients were enrolled in this study. Two patients achieved a confirmed PR, giving an ORR of 9% (95% CI 0.1–20.9%). An additional 7 patients achieved SD for at least 8 weeks. The median PFS was 11.8 weeks (95% CI 8.2–15.3).The median OS was 23.4 weeks (95% CI 14.7–32.1). Treatments were generally well tolerated. Sunitinib, as a single agent, had a substantial activity for Asian patients who had pretreated advanced NSCLC. The toxicity profile was favorable. However, large population and high-quality prospective clinical trials are needed to be conducted.
Similar content being viewed by others
References
Jemal A, Siegel R, Ward E, Hao Y, Xu J, et al. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–49.
Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003;9:669–76.
Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57–70.
O’Byrne KJ, Koukourakis MI, Giatromanolaki A, Cox G, Turley H, et al. Vascular endothelial growth factor, platelet-derived endothelial cell growth factor and angiogenesis in non-small-cell lung cancer. Br J Cancer. 2000;82:1427–32.
Shikada Y, Yonemitsu Y, Koga T, Onimaru M, Nakano T, et al. Platelet-derived growth factor-AA is an essential and autocrine regulator of vascular endothelial growth factor expression in non-small cell lung carcinomas. Cancer Res. 2005;65:7241–8.
Mendel DB, Laird AD, Xin X, Louie SG, Christensen JG, 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. 2003;9:327–37.
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;2:471–8.
O’Farrell AM, Abrams TJ, Yuen HA, Ngai TJ, Louie SG, et al. SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood. 2003;101:3597–605.
Potapova O, Laird AD, Nannini MA, Barone A, Li G, et al. Contribution of individual targets to the antitumor efficacy of the multitargeted receptor tyrosine kinase inhibitor SU11248. Mol Cancer Ther. 2006;5:1280–9.
Cella D, Michaelson MD, Bushmakin AG, Cappelleri JC, Charbonneau C, et al. Health-related quality of life in patients with metastatic renal cell carcinoma treated with sunitinib vs interferon-alpha in a phase III trial: final results and geographical analysis. Br J Cancer. 2010.
Castellano D, del Muro XG, Perez-Gracia JL, Gonzalez-Larriba JL, Abrio MV, et al. Patient-reported outcomes in a phase III, randomized study of sunitinib versus interferon-{alpha} as first-line systemic therapy for patients with metastatic renal cell carcinoma in a European population. Ann Oncol. 2009;20:1803–12.
Shirao K, Nishida T, Doi T, Komatsu Y, Muro K, et al. Phase I/II study of sunitinib malate in Japanese patients with gastrointestinal stromal tumor after failure of prior treatment with imatinib mesylate. Invest New Drugs. 2009.
Novello S, Scagliotti GV, Rosell R, Socinski MA, Brahmer J, et al. Phase II study of continuous daily sunitinib dosing in patients with previously treated advanced non-small cell lung cancer. Br J Cancer. 2009;101:1543–8.
Socinski MA, Novello S, Brahmer JR, Rosell R, Sanchez JM, et al. Multicenter, phase II trial of sunitinib in previously treated, advanced non-small-cell lung cancer. J Clin Oncol. 2008;26:650–6.
Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, 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;92:205–16.
Hotta K, Fujiwara Y, Kiura K, Takigawa N, Tabata M, et al. Relationship between response and survival in more than 50,000 patients with advanced non-small cell lung cancer treated with systemic chemotherapy in 143 phase III trials. J Thorac Oncol. 2007;2:402–7.
Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350:2129–39.
Conflict of interest statement
We disclose any financial and personal relationships with other people or organizations that could inappropriately influence our work. There is no conflict of interest related to the article or the research described.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ping, G., Hui-Min, W., Wei-Min, W. et al. Sunitinib in pretreated advanced non-small-cell lung carcinoma: a primary result from Asian population. Med Oncol 28, 578–583 (2011). https://doi.org/10.1007/s12032-010-9500-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12032-010-9500-9