Skip to main content
Top
Published in: BMC Urology 1/2014

Open Access 01-12-2014 | Research article

Organ-specific and tumor-size-dependent responses to sunitinib in clear cell renal cell carcinoma

Authors: Norihiko Tsuchiya, Takeshi Yuasa, Shinya Maita, Shintaro Narita, Takamitsu Inoue, Kazuyuki Numakura, Mitsuru Saito, Shigeru Satoh, Junji Yonese, Tomonori Habuchi

Published in: BMC Urology | Issue 1/2014

Login to get access

Abstract

Background

Tyrosine kinase inhibitors (TKIs) have been used as standard therapy for patients with advanced renal cell carcinoma (RCC). However, information on factors predicting response to treatment with TKIs is lacking. This study aimed to assess the association between initial tumor size, involved organs, pre-treatment C-reactive protein (CRP) levels, and reduction in tumor size in patients with clear cell RCC (CCRCC) treated with sunitinib.

Methods

Patients with advanced CCRCC with target lesions with a maximum diameter ≥ 10 mm treated with sunitinib were evaluated. The tumor diameter representing the best overall response was designated as the post-treatment tumor diameter.

Results

A total of 179 lesions in 38 patients were analyzed. Organ-specific analysis demonstrated that pre-treatment diameter of lung metastatic lesions had a moderate inverse association with percent reduction in post-treatment tumor diameter (R = 0.341). Lung lesions showed significantly greater percent reductions in diameter than liver and kidney lesions (P = 0.007 and 0.002, respectively). Furthermore, based on a CRP cut-off level of 2.0 mg/dl, mean tumor size reduction was significantly greater in patients with low CRP levels than in patients with high CRP levels in lesions with diameters < 20 mm (P = 0.002). CRP level had no effect on mean size reduction in lesions with a diameter ≥ 20 mm.

Conclusions

Patients with CCRCC with smaller lung metastatic lesions and lower CRP levels may achieve greater percent reductions in tumor size with sunitinib therapy than patients with extra-pulmonary lesions, large lung lesions, and/or higher CRP levels.
Appendix
Available only for authorised users
Literature
1.
go back to reference Akaza H, Kawai K, Tsukamoto T, Fujioka T, Tomita Y, Kitamura T, Ozono S, Miki T, Naito S, Zembutsu H: Successful outcomes using combination therapy of interleukin-2 and interferon-alpha for renal cell carcinoma patients with lung metastasis. Jpn J Clin Oncol. 2010, 40 (7): 684-689. 10.1093/jjco/hyq027.CrossRefPubMed Akaza H, Kawai K, Tsukamoto T, Fujioka T, Tomita Y, Kitamura T, Ozono S, Miki T, Naito S, Zembutsu H: Successful outcomes using combination therapy of interleukin-2 and interferon-alpha for renal cell carcinoma patients with lung metastasis. Jpn J Clin Oncol. 2010, 40 (7): 684-689. 10.1093/jjco/hyq027.CrossRefPubMed
2.
go back to reference Flanigan RC, Salmon SE, Blumenstein BA, Bearman SI, Roy V, McGrath PC, Caton JR, Munshi N, Crawford ED: Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med. 2001, 345 (23): 1655-1659. 10.1056/NEJMoa003013.CrossRefPubMed Flanigan RC, Salmon SE, Blumenstein BA, Bearman SI, Roy V, McGrath PC, Caton JR, Munshi N, Crawford ED: Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med. 2001, 345 (23): 1655-1659. 10.1056/NEJMoa003013.CrossRefPubMed
3.
go back to reference Albiges L, Oudard S, Negrier S, Caty A, Gravis G, Joly F, Duclos B, Geoffrois L, Rolland F, Guillot A, Laguerre B, Legouffe E, Kohser F, Dietrich PY, Theodore CA, Escudier B: Complete remission with tyrosine kinase inhibitors in renal cell carcinoma. J Clin Oncol. 2012, 30 (5): 482-487. 10.1200/JCO.2011.37.2516.CrossRefPubMed Albiges L, Oudard S, Negrier S, Caty A, Gravis G, Joly F, Duclos B, Geoffrois L, Rolland F, Guillot A, Laguerre B, Legouffe E, Kohser F, Dietrich PY, Theodore CA, Escudier B: Complete remission with tyrosine kinase inhibitors in renal cell carcinoma. J Clin Oncol. 2012, 30 (5): 482-487. 10.1200/JCO.2011.37.2516.CrossRefPubMed
4.
go back to reference Staehler M, Haseke N, Zilinberg E, Stadler T, Karl A, Siebels M, Durr HR, Siegert S, Jauch KW, Bruns CJ, Stief CG: Complete remission achieved with angiogenic therapy in metastatic renal cell carcinoma including surgical intervention. Urol Oncol. 2010, 28 (2): 139-144. 10.1016/j.urolonc.2009.03.033.CrossRefPubMed Staehler M, Haseke N, Zilinberg E, Stadler T, Karl A, Siebels M, Durr HR, Siegert S, Jauch KW, Bruns CJ, Stief CG: Complete remission achieved with angiogenic therapy in metastatic renal cell carcinoma including surgical intervention. Urol Oncol. 2010, 28 (2): 139-144. 10.1016/j.urolonc.2009.03.033.CrossRefPubMed
5.
go back to reference Krajewski KM, Guo M, Van den Abbeele AD, Yap J, Ramaiya N, Jagannathan J, Heng DY, Atkins MB, McDermott DF, Schutz FA, Pedrosa I, Choueiri TK: Comparison of four early posttherapy imaging changes (EPTIC; RECIST 1.0, tumor shrinkage, computed tomography tumor density, Choi criteria) in assessing outcome to vascular endothelial growth factor-targeted therapy in patients with advanced renal cell carcinoma. Eur Urol. 2011, 59 (5): 856-862. 10.1016/j.eururo.2011.01.038.CrossRefPubMed Krajewski KM, Guo M, Van den Abbeele AD, Yap J, Ramaiya N, Jagannathan J, Heng DY, Atkins MB, McDermott DF, Schutz FA, Pedrosa I, Choueiri TK: Comparison of four early posttherapy imaging changes (EPTIC; RECIST 1.0, tumor shrinkage, computed tomography tumor density, Choi criteria) in assessing outcome to vascular endothelial growth factor-targeted therapy in patients with advanced renal cell carcinoma. Eur Urol. 2011, 59 (5): 856-862. 10.1016/j.eururo.2011.01.038.CrossRefPubMed
6.
go back to reference Yuasa T, Urakami S, Yamamoto S, Yonese J, Nakano K, Kodaira M, Takahashi S, Hatake K, Inamura K, Ishikwa Y, Fukui I: Tumor size is a potential predictor of response to tyrosine kinase inhibitors in renal cell cancer. Urology. 2011, 77 (4): 831-835. 10.1016/j.urology.2010.12.008.CrossRefPubMed Yuasa T, Urakami S, Yamamoto S, Yonese J, Nakano K, Kodaira M, Takahashi S, Hatake K, Inamura K, Ishikwa Y, Fukui I: Tumor size is a potential predictor of response to tyrosine kinase inhibitors in renal cell cancer. Urology. 2011, 77 (4): 831-835. 10.1016/j.urology.2010.12.008.CrossRefPubMed
7.
go back to reference Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, Chen I, Bycott PW, Baum CM, Figlin RA: Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007, 356 (2): 115-124. 10.1056/NEJMoa065044.CrossRefPubMed Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, Chen I, Bycott PW, Baum CM, Figlin RA: Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007, 356 (2): 115-124. 10.1056/NEJMoa065044.CrossRefPubMed
8.
go back to reference Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Freeman S, Schwartz B, Shan M, Simantov R, Bukowski RM: Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007, 356 (2): 125-134. 10.1056/NEJMoa060655.CrossRefPubMed Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Freeman S, Schwartz B, Shan M, Simantov R, Bukowski RM: Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007, 356 (2): 125-134. 10.1056/NEJMoa060655.CrossRefPubMed
9.
go back to reference Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, Michaelson MD, Gorbunova VA, Gore ME, Rusakov IG, Negrier S, Ou YC, Castellano D, Lim HY, Uemura H, Tarazi J, Cella D, Chen C, Roosbrook B, Kim S, Motzer RJ: Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011, 378 (9807): 1931-1939. 10.1016/S0140-6736(11)61613-9.CrossRefPubMed Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, Michaelson MD, Gorbunova VA, Gore ME, Rusakov IG, Negrier S, Ou YC, Castellano D, Lim HY, Uemura H, Tarazi J, Cella D, Chen C, Roosbrook B, Kim S, Motzer RJ: Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011, 378 (9807): 1931-1939. 10.1016/S0140-6736(11)61613-9.CrossRefPubMed
10.
go back to reference Tannir NM, Plimack E, Ng C, Tamboli P, Bekele NB, Xiao L, Smith L, Lim Z, Pagliaro L, Araujo J, Aparicio A, Matin S, Wood CG, Jonasch E: A phase 2 trial of sunitinib in patients with advanced Non-clear cell renal cell carcinoma. Eur Urol. 2012, 62 (6): 1013-1019. 10.1016/j.eururo.2012.06.043.CrossRefPubMed Tannir NM, Plimack E, Ng C, Tamboli P, Bekele NB, Xiao L, Smith L, Lim Z, Pagliaro L, Araujo J, Aparicio A, Matin S, Wood CG, Jonasch E: A phase 2 trial of sunitinib in patients with advanced Non-clear cell renal cell carcinoma. Eur Urol. 2012, 62 (6): 1013-1019. 10.1016/j.eururo.2012.06.043.CrossRefPubMed
11.
go back to reference Chin AI, Lam JS, Figlin RA, Belldegrun AS: Surveillance strategies for renal cell carcinoma patients following nephrectomy. Rev Urol. 2006, 8 (1): 1-7.PubMedPubMedCentral Chin AI, Lam JS, Figlin RA, Belldegrun AS: Surveillance strategies for renal cell carcinoma patients following nephrectomy. Rev Urol. 2006, 8 (1): 1-7.PubMedPubMedCentral
12.
go back to reference Fujioka T, Obara W: Evidence-based clinical practice guideline for renal cell carcinoma: the Japanese Urological Association 2011 update. Int J Urol. 2012, 19 (6): 496-503. 10.1111/j.1442-2042.2012.03031.x.CrossRefPubMed Fujioka T, Obara W: Evidence-based clinical practice guideline for renal cell carcinoma: the Japanese Urological Association 2011 update. Int J Urol. 2012, 19 (6): 496-503. 10.1111/j.1442-2042.2012.03031.x.CrossRefPubMed
13.
go back to reference van der Veldt AA, Meijerink MR, van den Eertwegh AJ, Bex A, de Gast G, Haanen JB, Boven E: Sunitinib for treatment of advanced renal cell cancer: primary tumor response. Clin Cancer Res. 2008, 14 (8): 2431-2436. 10.1158/1078-0432.CCR-07-4089.CrossRefPubMed van der Veldt AA, Meijerink MR, van den Eertwegh AJ, Bex A, de Gast G, Haanen JB, Boven E: Sunitinib for treatment of advanced renal cell cancer: primary tumor response. Clin Cancer Res. 2008, 14 (8): 2431-2436. 10.1158/1078-0432.CCR-07-4089.CrossRefPubMed
14.
go back to reference Kroon BK, de Bruijn R, Prevoo W, Horenblas S, Powles T, Bex A: Probability of downsizing primary tumors of renal cell carcinoma by targeted therapies is related to size at presentation. Urology. 2012, 81 (1): 111-115.CrossRefPubMed Kroon BK, de Bruijn R, Prevoo W, Horenblas S, Powles T, Bex A: Probability of downsizing primary tumors of renal cell carcinoma by targeted therapies is related to size at presentation. Urology. 2012, 81 (1): 111-115.CrossRefPubMed
15.
go back to reference Abel EJ, Culp SH, Tannir NM, Tamboli P, Matin SF, Wood CG: Early primary tumor size reduction is an independent predictor of improved overall survival in metastatic renal cell carcinoma patients treated with sunitinib. Eur Urol. 2011, 60 (6): 1273-1279. 10.1016/j.eururo.2011.07.008.CrossRefPubMedPubMedCentral Abel EJ, Culp SH, Tannir NM, Tamboli P, Matin SF, Wood CG: Early primary tumor size reduction is an independent predictor of improved overall survival in metastatic renal cell carcinoma patients treated with sunitinib. Eur Urol. 2011, 60 (6): 1273-1279. 10.1016/j.eururo.2011.07.008.CrossRefPubMedPubMedCentral
16.
go back to reference Gabay C, Kushner I: Acute-phase proteins and other systemic responses to inflammation. N Engl J Med. 1999, 340 (6): 448-454. 10.1056/NEJM199902113400607.CrossRefPubMed Gabay C, Kushner I: Acute-phase proteins and other systemic responses to inflammation. N Engl J Med. 1999, 340 (6): 448-454. 10.1056/NEJM199902113400607.CrossRefPubMed
17.
go back to reference Bromwich E, McMillan DC, Lamb GW, Vasey PA, Aitchison M: The systemic inflammatory response, performance status and survival in patients undergoing alpha-interferon treatment for advanced renal cancer. Br J Cancer. 2004, 91 (7): 1236-1238. 10.1038/sj.bjc.6602152.CrossRefPubMedPubMedCentral Bromwich E, McMillan DC, Lamb GW, Vasey PA, Aitchison M: The systemic inflammatory response, performance status and survival in patients undergoing alpha-interferon treatment for advanced renal cancer. Br J Cancer. 2004, 91 (7): 1236-1238. 10.1038/sj.bjc.6602152.CrossRefPubMedPubMedCentral
18.
go back to reference Casamassima A, Picciariello M, Quaranta M, Berardino R, Ranieri C, Paradiso A, Lorusso V, Guida M: C-reactive protein: a biomarker of survival in patients with metastatic renal cell carcinoma treated with subcutaneous interleukin-2 based immunotherapy. J Urol. 2005, 173 (1): 52-55. 10.1097/01.ju.0000146713.50673.e5.CrossRefPubMed Casamassima A, Picciariello M, Quaranta M, Berardino R, Ranieri C, Paradiso A, Lorusso V, Guida M: C-reactive protein: a biomarker of survival in patients with metastatic renal cell carcinoma treated with subcutaneous interleukin-2 based immunotherapy. J Urol. 2005, 173 (1): 52-55. 10.1097/01.ju.0000146713.50673.e5.CrossRefPubMed
19.
go back to reference Ramsey S, Lamb GW, Aitchison M, Graham J, McMillan DC: Evaluation of an inflammation-based prognostic score in patients with metastatic renal cancer. Cancer. 2007, 109 (2): 205-212. 10.1002/cncr.22400.CrossRefPubMed Ramsey S, Lamb GW, Aitchison M, Graham J, McMillan DC: Evaluation of an inflammation-based prognostic score in patients with metastatic renal cancer. Cancer. 2007, 109 (2): 205-212. 10.1002/cncr.22400.CrossRefPubMed
20.
go back to reference Yasuda Y, Saito K, Yuasa T, Kitsukawa S, Urakami S, Yamamoto S, Yonese J, Takahashi S, Fukui I: Prognostic impact of pretreatment C-reactive protein for patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors. Int J Clin Oncol. 2012, 18 (5): 884-889.CrossRefPubMed Yasuda Y, Saito K, Yuasa T, Kitsukawa S, Urakami S, Yamamoto S, Yonese J, Takahashi S, Fukui I: Prognostic impact of pretreatment C-reactive protein for patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors. Int J Clin Oncol. 2012, 18 (5): 884-889.CrossRefPubMed
21.
go back to reference Slaviero KA, Clarke SJ, Rivory LP: Inflammatory response: an unrecognised source of variability in the pharmacokinetics and pharmacodynamics of cancer chemotherapy. Lancet Oncol. 2003, 4 (4): 224-232. 10.1016/S1470-2045(03)01034-9.CrossRefPubMed Slaviero KA, Clarke SJ, Rivory LP: Inflammatory response: an unrecognised source of variability in the pharmacokinetics and pharmacodynamics of cancer chemotherapy. Lancet Oncol. 2003, 4 (4): 224-232. 10.1016/S1470-2045(03)01034-9.CrossRefPubMed
22.
go back to reference Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J: New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009, 45 (2): 228-247. 10.1016/j.ejca.2008.10.026.CrossRefPubMed Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J: New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009, 45 (2): 228-247. 10.1016/j.ejca.2008.10.026.CrossRefPubMed
23.
go back to reference Han KS, Jung DC, Choi HJ, Jeong MS, Cho KS, Joung JY, Seo HK, Lee KH, Chung J: Pretreatment assessment of tumor enhancement on contrast-enhanced computed tomography as a potential predictor of treatment outcome in metastatic renal cell carcinoma patients receiving antiangiogenic therapy. Cancer. 2010, 116 (10): 2332-2342.PubMed Han KS, Jung DC, Choi HJ, Jeong MS, Cho KS, Joung JY, Seo HK, Lee KH, Chung J: Pretreatment assessment of tumor enhancement on contrast-enhanced computed tomography as a potential predictor of treatment outcome in metastatic renal cell carcinoma patients receiving antiangiogenic therapy. Cancer. 2010, 116 (10): 2332-2342.PubMed
24.
go back to reference Nathan PD, Vinayan A, Stott D, Juttla J, Goh V: CT response assessment combining reduction in both size and arterial phase density correlates with time to progression in metastatic renal cancer patients treated with targeted therapies. Cancer Biol Ther. 2010, 9 (1): 15-19. 10.4161/cbt.9.1.10340.CrossRefPubMed Nathan PD, Vinayan A, Stott D, Juttla J, Goh V: CT response assessment combining reduction in both size and arterial phase density correlates with time to progression in metastatic renal cancer patients treated with targeted therapies. Cancer Biol Ther. 2010, 9 (1): 15-19. 10.4161/cbt.9.1.10340.CrossRefPubMed
25.
go back to reference Hittinger M, Staehler M, Schramm N, Ubleis C, Becker C, Reiser M, Berger F: Course of size and density of metastatic renal cell carcinoma lesions in the early follow-up of molecular targeted therapy. Urol Oncol. 2012, 30 (5): 695-703. 10.1016/j.urolonc.2010.10.011.CrossRefPubMed Hittinger M, Staehler M, Schramm N, Ubleis C, Becker C, Reiser M, Berger F: Course of size and density of metastatic renal cell carcinoma lesions in the early follow-up of molecular targeted therapy. Urol Oncol. 2012, 30 (5): 695-703. 10.1016/j.urolonc.2010.10.011.CrossRefPubMed
26.
go back to reference Choi H, Charnsangavej C, Faria SC, Macapinlac HA, Burgess MA, Patel SR, Chen LL, Podoloff DA, Benjamin RS: Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: proposal of new computed tomography response criteria. J Clin Oncol. 2007, 25 (13): 1753-1759. 10.1200/JCO.2006.07.3049.CrossRefPubMed Choi H, Charnsangavej C, Faria SC, Macapinlac HA, Burgess MA, Patel SR, Chen LL, Podoloff DA, Benjamin RS: Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: proposal of new computed tomography response criteria. J Clin Oncol. 2007, 25 (13): 1753-1759. 10.1200/JCO.2006.07.3049.CrossRefPubMed
Metadata
Title
Organ-specific and tumor-size-dependent responses to sunitinib in clear cell renal cell carcinoma
Authors
Norihiko Tsuchiya
Takeshi Yuasa
Shinya Maita
Shintaro Narita
Takamitsu Inoue
Kazuyuki Numakura
Mitsuru Saito
Shigeru Satoh
Junji Yonese
Tomonori Habuchi
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Urology / Issue 1/2014
Electronic ISSN: 1471-2490
DOI
https://doi.org/10.1186/1471-2490-14-26

Other articles of this Issue 1/2014

BMC Urology 1/2014 Go to the issue