Skip to main content
Top
Published in: Investigational New Drugs 6/2012

01-12-2012 | REVIEW

Predictive factors for response to treatment in patients with advanced renal cell carcinoma

Authors: Carolina Muriel López, Emilio Esteban, Aurora Astudillo, Pablo Pardo, Jose Pablo Berros, Marta Izquierdo, Guillermo Crespo, Paula J. Fonseca, Miguel Sanmamed, Pablo Martínez-Camblor

Published in: Investigational New Drugs | Issue 6/2012

Login to get access

Summary

Introduction The analysis of predictive factors of response may aid in predicting which patients with advanced renal cell carcinoma (RCC) would be good candidates for systemic treatments. Materials and methods The expression of several biomarkers was retrospectively analyzed using immunohistochemistry (IHC), as well as 2 analytical variables in 135 patients with advanced RCC treated with cytokines (CK) and/or new targeted drugs (NTD). Results 67 patients were treated solely with NTD and 68 with CK (23 also received NTD). Univariate analysis: HIF1α did not correlate significantly with response to these drugs. Overexpression of CAIX was associated with more responses (%) to NTD (64.7 vs. 21.1; p = 0.004) and CK (22.6 vs. 0; p = 0.038). PTEN demonstrated predictive value of response to sunitinib (70.8 vs. 34.1; p = 0.005). p21 was associated with a lower response to sunitinib (35.9 vs. 65.4; p = 0.025). Thrombocytosis was not significantly associated with response to NTD, although it was with CK (0 vs. 20; p = 0.017). Neutrophilia correlated with a lower response to NTD (29.6 vs. 57.5; p = 0.045), although not with CK. Multivariate analysis: Overexpression of CAIX was an independent predictor of significantly higher response to NTD and CK; OR = 8.773 (p < 0.001). Conclusions Our findings highlight the usefulness of CAIX in selecting patients with advanced RCC as candidates for systemic treatment. PTEN and p21 may be important in predicting response to sunitinib. Thrombocytosis and neutrophilia correlate well with response to CK and NTD, respectively.
Literature
2.
go back to reference Jemal A, Murria T, Ward E, Samuels A, Tiwari RC (2005) Cancer statistics. Cancer J Clin 55:10–30CrossRef Jemal A, Murria T, Ward E, Samuels A, Tiwari RC (2005) Cancer statistics. Cancer J Clin 55:10–30CrossRef
3.
go back to reference McLaughlin JK, Lipworth L (2000) Epidemiologic aspects of renal cell cancer. Semin Oncol 27:115–123PubMed McLaughlin JK, Lipworth L (2000) Epidemiologic aspects of renal cell cancer. Semin Oncol 27:115–123PubMed
4.
go back to reference Greenlee RT, Murray T, Bolden S et al (2000) Cancer statistics Cancer J Clin 50. Greenlee RT, Murray T, Bolden S et al (2000) Cancer statistics Cancer J Clin 50.
5.
go back to reference Vinels P, Alavanja M, Buffer P et al (2004) Tobacco and cancer: recent epidemiological evidence. J Natl Cancer Inst 96:99–106CrossRef Vinels P, Alavanja M, Buffer P et al (2004) Tobacco and cancer: recent epidemiological evidence. J Natl Cancer Inst 96:99–106CrossRef
6.
go back to reference Maclurem WW (1990) A case control study of diet and risk of renal adenocarcinoma. Epidemiology 1:430CrossRef Maclurem WW (1990) A case control study of diet and risk of renal adenocarcinoma. Epidemiology 1:430CrossRef
7.
go back to reference Hunt JD, van der Hel OL, McMillan GP et al (2005) Renal cell carcinoma en relation to cigarette smoking: meta-analysis of 24 studies. Int J Cancer 114:101–108PubMedCrossRef Hunt JD, van der Hel OL, McMillan GP et al (2005) Renal cell carcinoma en relation to cigarette smoking: meta-analysis of 24 studies. Int J Cancer 114:101–108PubMedCrossRef
8.
go back to reference Bergstrom A, Hsich CC, Lindbland P et al (2001) Obesity and renal cell cancer: a quantitative review. Br J Cancer 85:984–990PubMedCrossRef Bergstrom A, Hsich CC, Lindbland P et al (2001) Obesity and renal cell cancer: a quantitative review. Br J Cancer 85:984–990PubMedCrossRef
9.
go back to reference Bergstrom A, Pisani P, Tenet V et al (2001) Overweight as an avoidable cause of cancer in Europe. Int J Cancer 91:421–430PubMedCrossRef Bergstrom A, Pisani P, Tenet V et al (2001) Overweight as an avoidable cause of cancer in Europe. Int J Cancer 91:421–430PubMedCrossRef
10.
go back to reference Calle EE, Kaasks R (2004) Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 4:579–591PubMedCrossRef Calle EE, Kaasks R (2004) Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 4:579–591PubMedCrossRef
11.
go back to reference Wolchok JD, Motzer RJ (2000) Management of renal cell carcinoma. Oncology 14:29–34PubMed Wolchok JD, Motzer RJ (2000) Management of renal cell carcinoma. Oncology 14:29–34PubMed
12.
go back to reference Medical Research Council Renal Cancer Collaborators (1999) Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomised controlled trial. Lancet 353:14–17CrossRef Medical Research Council Renal Cancer Collaborators (1999) Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomised controlled trial. Lancet 353:14–17CrossRef
13.
go back to reference Yang JC, Sherry RM, Steinberg SM et al (2003) Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. J Clin Oncol 21:3127–3132PubMedCrossRef Yang JC, Sherry RM, Steinberg SM et al (2003) Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. J Clin Oncol 21:3127–3132PubMedCrossRef
14.
go back to reference Motzer RJ, Hutson TE, Tomczak P et al (2007) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356:115–124PubMedCrossRef Motzer RJ, Hutson TE, Tomczak P et al (2007) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356:115–124PubMedCrossRef
15.
go back to reference Escudier B, Szezylik C, Eisen T et al (2007) Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356:125–134PubMedCrossRef Escudier B, Szezylik C, Eisen T et al (2007) Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356:125–134PubMedCrossRef
16.
go back to reference Hudes G, Carducci M, Tomczak P et al (2007) Temsirolimus, interferon alpha, or both for advanced renal-cell carcinoma. N Engl J Med 356:2271–2281PubMedCrossRef Hudes G, Carducci M, Tomczak P et al (2007) Temsirolimus, interferon alpha, or both for advanced renal-cell carcinoma. N Engl J Med 356:2271–2281PubMedCrossRef
17.
go back to reference Escudier BJ, Bellmunt J, Negrier S et al (2009) Final results of the phase III, randomized, double-blind AVOREN trial of first-line bevacizumab (BEV) + interferon-α2a (IFN) in metastatic renal cell carcinoma (mRCC). J Clin Oncol 27:15s (suppl; abstr 5020) Escudier BJ, Bellmunt J, Negrier S et al (2009) Final results of the phase III, randomized, double-blind AVOREN trial of first-line bevacizumab (BEV) + interferon-α2a (IFN) in metastatic renal cell carcinoma (mRCC). J Clin Oncol 27:15s (suppl; abstr 5020)
18.
go back to reference Motzer RJ, Escudier B, Oudard S, RECORD-1. Study Group et al (2008) Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 372(9637):449–456PubMedCrossRef Motzer RJ, Escudier B, Oudard S, RECORD-1. Study Group et al (2008) Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 372(9637):449–456PubMedCrossRef
19.
go back to reference Sternberg CN, Davis ID, Mardiak J et al (2010) Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 28(6):1061–1068PubMedCrossRef Sternberg CN, Davis ID, Mardiak J et al (2010) Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 28(6):1061–1068PubMedCrossRef
20.
go back to reference Bui MH, Seligson D, Han KR et al (2003) Carbonic anhydrase IX is an independent predictor of survival in advanced renal clear cell carcinoma: Implications for prognosis and therapy. Clin Cancer Res 9:802–811PubMed Bui MH, Seligson D, Han KR et al (2003) Carbonic anhydrase IX is an independent predictor of survival in advanced renal clear cell carcinoma: Implications for prognosis and therapy. Clin Cancer Res 9:802–811PubMed
21.
go back to reference Hager M, Haufe H, Kemmerling R et al (2007) PTEN expression in renal cell carcinoma and oncocytoma and prognosis. Pathology 39:482–485PubMedCrossRef Hager M, Haufe H, Kemmerling R et al (2007) PTEN expression in renal cell carcinoma and oncocytoma and prognosis. Pathology 39:482–485PubMedCrossRef
22.
go back to reference Bozhurt SU, Avan E, Bolukbasi F et al (2009) Immunohistochemical expression of SPARC is correlated with recurrence, survival and malignant potential in meningiomas. APMIS 117(9):651–659CrossRef Bozhurt SU, Avan E, Bolukbasi F et al (2009) Immunohistochemical expression of SPARC is correlated with recurrence, survival and malignant potential in meningiomas. APMIS 117(9):651–659CrossRef
23.
go back to reference Zoblec I, Steele R, Terracciano L et al (2007) Selecting immunohistochemical cut-off scores for novel biomarkers of progression and survival in colorectal cancer. J Clin Pathol 60(10):1112–1116CrossRef Zoblec I, Steele R, Terracciano L et al (2007) Selecting immunohistochemical cut-off scores for novel biomarkers of progression and survival in colorectal cancer. J Clin Pathol 60(10):1112–1116CrossRef
25.
go back to reference Miller AB, Hooqstraten B, Staquet M et al (1958) Reporting results of cancer treatment. Cancer 47:207–214CrossRef Miller AB, Hooqstraten B, Staquet M et al (1958) Reporting results of cancer treatment. Cancer 47:207–214CrossRef
26.
go back to reference Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observation. J Am Stat Assoc 53:457–481CrossRef Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observation. J Am Stat Assoc 53:457–481CrossRef
27.
go back to reference Motzer RJ, Mazumdar M, Bacik J et al (1999) Survival and prognostic factors stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol 17(8):2530–2540PubMed Motzer RJ, Mazumdar M, Bacik J et al (1999) Survival and prognostic factors stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol 17(8):2530–2540PubMed
28.
go back to reference Motzer RJ, Bacik J, Murphy BA et al (2002) Interferon-α as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol 20:286–296 Motzer RJ, Bacik J, Murphy BA et al (2002) Interferon-α as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol 20:286–296
29.
go back to reference Mekhail TM, Abou-Jawde RM, BouMerhi G et al (2005) Validation and extension of the Memorial Sloan-Kettering Prognostic Factors Model for Survival in patients with previously untreated metastatic renal cell carcinoma. J Clin Oncol 23:832–841PubMedCrossRef Mekhail TM, Abou-Jawde RM, BouMerhi G et al (2005) Validation and extension of the Memorial Sloan-Kettering Prognostic Factors Model for Survival in patients with previously untreated metastatic renal cell carcinoma. J Clin Oncol 23:832–841PubMedCrossRef
30.
go back to reference Unruh A, Ressel A, Mohamed HG et al (2003) The hypoxia-inducible factor-1 is a negative factor for tumor therapy. Oncogene 22:3213–3220PubMedCrossRef Unruh A, Ressel A, Mohamed HG et al (2003) The hypoxia-inducible factor-1 is a negative factor for tumor therapy. Oncogene 22:3213–3220PubMedCrossRef
31.
go back to reference Brugarolas J (2007) Renal-cell carcinoma-molecular pathways and therapies. N Engl J Med 356:185–187PubMedCrossRef Brugarolas J (2007) Renal-cell carcinoma-molecular pathways and therapies. N Engl J Med 356:185–187PubMedCrossRef
32.
go back to reference Patel PH, Chadalavada RS, Ishill NM et al (2008) Hypoxia-inducible factor (HIF) 1α and 2α levels in cell lines and human tumor predicts response to sunitinib in renal cell carcinoma (RCC). J Clin Oncol 26 (abstr. 5008) Patel PH, Chadalavada RS, Ishill NM et al (2008) Hypoxia-inducible factor (HIF) 1α and 2α levels in cell lines and human tumor predicts response to sunitinib in renal cell carcinoma (RCC). J Clin Oncol 26 (abstr. 5008)
33.
go back to reference Bui MH, Seligson D, Han KR et al (2003) Carbonic anhydrase IX is an independent predictor of survival in advanced renal clear cell carcinoma: Implications for prognosis and therapy. Clin Cancer Res 9:802–811PubMed Bui MH, Seligson D, Han KR et al (2003) Carbonic anhydrase IX is an independent predictor of survival in advanced renal clear cell carcinoma: Implications for prognosis and therapy. Clin Cancer Res 9:802–811PubMed
34.
go back to reference Patard J-J, Fergelot P, Karakiewicz PI et al (2008) Low CAIX expression and absence of VHL gene mutation are associated with tumor aggressiveness and poor survival of clear cell renal cell carcinoma. Int J Carncer 123:395–400CrossRef Patard J-J, Fergelot P, Karakiewicz PI et al (2008) Low CAIX expression and absence of VHL gene mutation are associated with tumor aggressiveness and poor survival of clear cell renal cell carcinoma. Int J Carncer 123:395–400CrossRef
35.
go back to reference Atkins M, Regan M, McDermott D et al (2005) Carbonic anhydrase IX expression predicts outcome of interleukin 2 therapy for renal cancer. Clin Cancer Res 11:3714–3721PubMedCrossRef Atkins M, Regan M, McDermott D et al (2005) Carbonic anhydrase IX expression predicts outcome of interleukin 2 therapy for renal cancer. Clin Cancer Res 11:3714–3721PubMedCrossRef
36.
go back to reference Klatte T, Zomorodian N, Kabbinavar FF et al (2007) Prospective evaluation of carbonic anhydrase IX (CAIX) as a molecular marker in metastatic renal cell carcinoma. J Clin Oncol 25 (abstr. 5112) Klatte T, Zomorodian N, Kabbinavar FF et al (2007) Prospective evaluation of carbonic anhydrase IX (CAIX) as a molecular marker in metastatic renal cell carcinoma. J Clin Oncol 25 (abstr. 5112)
37.
go back to reference Signoretti S, Regan M, Atkins M (2008) Carbonic anhydrase IX as a predictive biomarker of response to kidney cancer therapy. BJU Int 101(Suppl 4):31–35PubMedCrossRef Signoretti S, Regan M, Atkins M (2008) Carbonic anhydrase IX as a predictive biomarker of response to kidney cancer therapy. BJU Int 101(Suppl 4):31–35PubMedCrossRef
38.
go back to reference Choueiri TK, Regan MM, Brick AJ et al (2008) Carbonic anhydrase IX (CAIX) and pathologic features as predictors of outcome in patients with metastatic renal cell carcinoma receiving VEGF-targeted therapy. ASCO Annual Meeting J Clin Oncol 26(Suppl 20):16042 Choueiri TK, Regan MM, Brick AJ et al (2008) Carbonic anhydrase IX (CAIX) and pathologic features as predictors of outcome in patients with metastatic renal cell carcinoma receiving VEGF-targeted therapy. ASCO Annual Meeting J Clin Oncol 26(Suppl 20):16042
39.
go back to reference Choueiri TK, Vaziri SA, Rini I et al (2007) Use of Von-Hippel Lindau (VHL) mutation status to predict objective response to vascular endothelial growth factor (VEGF)-targeted therapy in metastatic renal cell carcinoma (RCC). ASCO Annual Meeting Proceedings Part I. J Clin Oncol 25:5012 Choueiri TK, Vaziri SA, Rini I et al (2007) Use of Von-Hippel Lindau (VHL) mutation status to predict objective response to vascular endothelial growth factor (VEGF)-targeted therapy in metastatic renal cell carcinoma (RCC). ASCO Annual Meeting Proceedings Part I. J Clin Oncol 25:5012
40.
go back to reference Fan Y, Borowsky AD, Weiss RH (2003) An antisense oligodeoxynucleotide to p21 (Waf1/Cip1) causes apoptosis in human breast cancer cells. Mol Cancer Ther 2:773 Fan Y, Borowsky AD, Weiss RH (2003) An antisense oligodeoxynucleotide to p21 (Waf1/Cip1) causes apoptosis in human breast cancer cells. Mol Cancer Ther 2:773
41.
go back to reference Weiss RH (2003) p21 Waf1/Cip1 as a therapeutic target in breast and other cancers. Cancer Cell 4:425 Weiss RH (2003) p21 Waf1/Cip1 as a therapeutic target in breast and other cancers. Cancer Cell 4:425
42.
go back to reference Hollen CW, Henthorn J, Koziol JA et al (1992) Serum interleukin-6 levels in patients with thrombocytosis. Leuk Lymphoma 8:235–241 Hollen CW, Henthorn J, Koziol JA et al (1992) Serum interleukin-6 levels in patients with thrombocytosis. Leuk Lymphoma 8:235–241
43.
go back to reference Donskov F, Von der Maase H (2006) Impact of immune parameters on long-term survival in metastatic renal cell carcinoma. J Clin Oncol 24:1997–2005 Donskov F, Von der Maase H (2006) Impact of immune parameters on long-term survival in metastatic renal cell carcinoma. J Clin Oncol 24:1997–2005
Metadata
Title
Predictive factors for response to treatment in patients with advanced renal cell carcinoma
Authors
Carolina Muriel López
Emilio Esteban
Aurora Astudillo
Pablo Pardo
Jose Pablo Berros
Marta Izquierdo
Guillermo Crespo
Paula J. Fonseca
Miguel Sanmamed
Pablo Martínez-Camblor
Publication date
01-12-2012
Publisher
Springer US
Published in
Investigational New Drugs / Issue 6/2012
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI
https://doi.org/10.1007/s10637-012-9836-4

Other articles of this Issue 6/2012

Investigational New Drugs 6/2012 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine