Outcome of third‑line sunitinib after sequential therapy with cytokines and sorafenib in metastatic renal cell carcinoma

Fujita,Tetsuo; Hirayama,Takahiro; Nishi,Morihiro; Matsumoto,Kazumasa; Yoshida,Kazunari; Iwamura,Masatsugu

doi:10.3892/mco.2019.1924

Outcome of third‑line sunitinib after sequential therapy with cytokines and sorafenib in metastatic renal cell carcinoma

Authors:
- Tetsuo Fujita
- Takahiro Hirayama
- Morihiro Nishi
- Kazumasa Matsumoto
- Kazunari Yoshida
- Masatsugu Iwamura
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Affiliations: Department of Urology, Kitasato University School of Medicine, Sagamihara, Kanagawa 252‑0374, Japan
Published online on: September 18, 2019 https://doi.org/10.3892/mco.2019.1924
Pages: 505-510

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Abstract

Third‑line sunitinib is occasionally used for selected patients with metastatic renal cell carcinoma (mRCC). The aim of the present study was to evaluate the clinical significance of third‑line sunitinib after failure of first‑line cytokine therapy and second‑line sorafenib in patients with clear‑cell mRCC. A total of 14 consecutive patients with clear‑cell mRCC treated with third‑line sunitinib between December 2008 and February 2012 were enrolled in the present study. Disease control rate (DCR), progression‑free survival (PFS), overall survival (OS), and relative dose intensity (RDI) were compared with those of first‑line (n=20) and second‑line (n=14) sunitinib treatment. The DCR was 42.9%, the median PFS was 12.0 months, and the median OS was 20.0 months for third‑line sunitinib; there were no statistically significant differences compared with first‑line and second‑line sunitinib. The mean RDI was significantly lower for third‑line sunitinib compared with first‑ and second‑line sunitinib (P=0.0003 and 0.0109, respectively). Therefore, third‑line sunitinib is an effective treatment option for selected patients with mRCC, as optimized therapeutic efficacy was obtained with a relatively low dose of sunitinib.

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1	Garcia JA and Rini BI: Recent progress in the management of advanced renal cell carcinoma. CA Cancer J Clin. 57:112–125. 2007. View Article : Google Scholar : PubMed/NCBI
2	Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, et al: Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 356:115–124. 2007. View Article : Google Scholar : PubMed/NCBI
3	Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Oudard S, Negrier S, Szczylik C, Pili R, Bjarnason GA, et al: Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol. 27:3584–3590. 2009. View Article : Google Scholar : PubMed/NCBI
4	Naito S, Yamamoto N, Takayama T, Muramoto M, Shinohara N, Nishiyama K, Takahashi A, Maruyama R, Saika T, Hoshi S, et al: Prognosis of Japanese metastatic renal cell carcinoma patients in the cytokine era: A cooperative group report of 1463 patients. Eur Urol. 57:317–326. 2010. View Article : Google Scholar : PubMed/NCBI
5	Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, et al: Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 356:125–134. 2007. View Article : Google Scholar : PubMed/NCBI
6	General rule for clinical and pathological studies on renal cell carcinoma, the 4th edition, . The Japanese Urological Association, The Japanese Society of Pathology, Japan Radiological Society. 2011.
7	Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, 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 : PubMed/NCBI
8	National Cancer Institute, . Cancer Therapy Evaluation Program. https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40July 5–2019
9	Eichelberg C, Heuer R, Chun FK, Hinrichs K, Zacharias M, Huland H and Heinzer H: Sequential use of the tyrosine kinase inhibitors sorafenib and sunitinib in metastatic renal cell carcinoma: A retrospective outcome analysis. Eur Urol. 54:1373–1378. 2008. View Article : Google Scholar : PubMed/NCBI
10	Dudek AZ, Zolnierek J, Dham A, Lindgren BR and Szczylik C: Sequential therapy with sorafenib and sunitinib in renal cell carcinoma. Cancer. 115:61–67. 2009. View Article : Google Scholar : PubMed/NCBI
11	Sablin MP, Negrier S, Ravaud A, Oudard S, Balleyguier C, Gautier J, Celier C, Medioni J and Escudier B: Sequential sorafenib and sunitinib for renal cell carcinoma. J Urol. 182:29–34. 2009. View Article : Google Scholar : PubMed/NCBI
12	Miyake H, Kusuda Y, Harada K, Sakai I and Fujisawa M: 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. View Article : Google Scholar : PubMed/NCBI
13	Mizukami Y, Kohgo Y and Chung DC: Hypoxia inducible factor-1 independent pathways in tumor angiogenesis. Clin Cancer Res. 13:5670–5674. 2007. View Article : Google Scholar : PubMed/NCBI
14	Motzer RJ, Bacik J, Murphy BA, Russo P and Mazumdar M: Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol. 20:289–296. 2002. View Article : Google Scholar : PubMed/NCBI
15	Fujita T, Iwamura M, Ishii D, Tabata K, Matsumoto K, Yoshida K and Baba S: C-reactive protein as a prognostic marker for advanced renal cell carcinoma treated with sunitinib. Int J Urol. 19:908–913. 2012. View Article : Google Scholar : PubMed/NCBI
16	Gore ME, Szczylik C, Porta C, Bracarda S, Bjamason GA, Oudard S, Hariharan S, Lee SH, Haanen J, Castellano D, et al: Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: An expanded-access trial. Lancet Oncol. 10:757–763. 2009. View Article : Google Scholar : PubMed/NCBI
17	Kawashima A, Tsujimura A, Takayama H, Arai Y, Nin M, Tanigawa G, Yasunaga Y, Mukai M, Uemura M, Nakai Y, et al: Importance of continuing therapy and maintaining one-month relative dose intensity in sunitinib therapy for metastatic renal cell carcinoma. Med Oncol. 29:3298–3305. 2012. View Article : Google Scholar : PubMed/NCBI
18	Porta C, Procopio G, Cartenì G, Sabbatini R, Bearz A, Chiappino I, Ruggeri EM, Re GL, Ricotta R, Zustovich F, et al: Sequential use of sorafenib and sunitinib in advanced renal-cell carcinoma (RCC): An Italian multicentre retrospective analysis of 189 patient cases. BJU Int. 108:E250–E257. 2011. View Article : Google Scholar : PubMed/NCBI
19	Stenner F, Chastonay R, Liewen H, Haile SR, Cathomas R, Rothermundt C, Siciliano RD, Stoll S, Knuth A, Buchler T, et al: A pooled analysis of sequential therapies with sorafenib and sunitinib in metastatic renal cell carcinoma. Oncology. 82:333–340. 2012. View Article : Google Scholar : PubMed/NCBI