Abstract
Background
The aim of this study was to evaluate the use of sunitinib as third-line therapy for metastatic renal cell carcinoma (mRCC).
Methods
This study included a total of 35 consecutive Japanese patients with mRCC who were treated with third-line sunitinib after sequential use of cytokine therapy (interferon-α and/or interleukin-2) and sorafenib between September 2008 and December 2010. The clinical outcomes of third-line sunitinib in these patients were retrospectively reviewed.
Results
Of the 35 patients, 3 (8.6%), 28 (80.0%) and 4 (11.4%) were judged to have a partial response, stable disease and progressive disease, respectively, as the best response to sunitinib. The median progression-free survival (PFS) and overall survival (OS) of these patients following the introduction of sunitinib were 10.9 and 14.2 months, respectively. Of several factors examined, response to sorafenib and performance status appeared to be independently associated with PFS and OS, respectively, on multivariate analyses. The common grade 3–4 adverse events related to third-line sunitinib were thrombocytopenia (51.4%), neutropenia (42.9%) and hypertension (14.3%).
Conclusion
Despite the low response rate, third-line sunitinib is well tolerated and could provide comparatively favorable prognostic outcomes in Japanese patients with mRCC after first-line cytokine therapy and second-line sorafenib; therefore, treatment with sunitinib could be one on the therapeutic options for patients with mRCC even after the failure of sequentially performed systemic therapies, such as cytokine therapy and sorafenib.
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References
Parton M, Gore M, Eisen T (2006) Role of cytokine therapy in 2006 and beyond for metastatic renal cell cancer. J Clin Oncol 24:5584–5592
Bellmunt J, Montagut C, Albiol S et al (2007) Present strategies in the treatment of metastatic renal cell carcinoma: an update on molecular targeting agents. BJU Int 99:274–280
Lane BR, Rini BI, Novick AC et al (2007) Targeted molecular therapy for renal cell carcinoma. Urology 69:3–10
Hutson TE, Figlin RA, Kuhn JG et al (2008) Targeted therapies for metastatic renal cell carcinoma: an overview of toxicity and dosing strategies. Oncologist 13:1084–1096
Naito S, Yamamoto N, Takayama T et al (2010) Prognosis of Japanese metastatic renal cell carcinoma patients in the cytokine era: a cooperative group report of 1463 patients. Eur Urol 57:317–325
Akaza H, Kawai K, Tsukamoto T et al (2010) Successful outcomes using combination therapy of interleukin-2 and interferon-alpha for renal cell carcinoma patients with lung metastasis. Jpn J Clin Oncol 40:684–689
Miyake H, Kurahashi T, Takenaka A et al (2009) Clinical outcome of combined immunotherapy with interferon-alpha and low-dose interleukine-2 for Japanese patients with metastatic renal cell carcinoma. Urol Oncol 27:598–603
Motzer RJ, Bacik J, Murphy BA et al (2002) Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol 20:289–296
Reeves DJ, Liu CY (2009) Treatment of metastatic renal cell carcinoma. Cancer Chemother Pharmacol 64:11–25
Mendel DB, Laird AD, Xin X et al (2003) 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
Motzer RJ, Hutson TE, Tomczak P et al (2009) Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol 27:3584–3590
Escudier B, Eisen T, Stadler WM et al (2007) Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356:125–134
Naito S, Tsukamoto T, Murai M (2011) Overall survival and good tolerability of long-term use of sorafenib after cytokine treatment: final results of a phase II trial of sorafenib in Japanese patients with metastatic renal cell carcinoma. BJU Int (in press). doi:10.1111/j.1464-410X.2011.10281.x
Dudek AZ, Zolnierek J, Dham A et al (2009) Sequential therapy with sorafenib and sunitinib in renal cell carcinoma. Cancer 115:61–67
Sablin MP, Negrier S, Ravaud A et al (2009) Sequential sorafenib and sunitinib for renal cell carcinoma. J Urol 182:29–34
Elfiky AA, Cho DC, McDermott DF et al (2010) Predictors of response to sequential sunitinib and the impact of prior VEGF-targeted drug washout in patients with metastatic clear-cell renal cell carcinoma. Urol Oncol (in press). doi:10.1016/j.urolonc.2010.01.008
Uemura H, Shinohara N, Yuasa T et al (2010) A phase II study of sunitinib in Japanese patients with metastatic renal cell carcinoma: insights into the treatment, efficacy and safety. Jpn J Clin Oncol 40:194–202
Rini BI (2010) New strategies in kidney cancer: therapeutic advances through understanding the molecular basis of response and resistance. Clin Cancer Res 16:1348–1354
Di Lorenzo G, Buonerba C, Federico P et al (2010) Third-line sorafenib after sequential therapy with sunitinib and mTOR inhibitors in metastatic renal cell carcinoma. Eur Urol 58:906–911
Mackenzie MJ, Rini BI, Elson P et al (2011) Temsirolimus in VEGF-refractory metastatic renal cell carcinoma. Ann Oncol 22:145–148
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Miyake, H., Kusuda, Y., Harada, Ki. et al. Third-line sunitinib following sequential use of cytokine therapy and sorafenib in Japanese patients with metastatic renal cell carcinoma. Int J Clin Oncol 18, 81–86 (2013). https://doi.org/10.1007/s10147-011-0347-7
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DOI: https://doi.org/10.1007/s10147-011-0347-7