Risk stratification and prognostication of renal cell carcinoma

World Journal of Urology

Volumn 26, Issue 2, 2008, Pages 115-125

  Ficarra, Vincenzo ^a   Galfano, Antonio ^a   Novara, Giacomo ^a,b   Iafrate, Massimo ^a   Brunelli, Matteo ^c   Secco, Silvia ^a   Cavalleri, Stefano ^a   Martignoni, Guido ^c   Artibani, Walter ^a  

^a UNIVERSITY OF PADOVA   (Italy)

^b VENETO INSTITUTE OF ONCOLOGY IOV IRCCS   (Italy)

^c UNIVERSITY OF VERONA   (Italy)

Author keywords

Cancer specific survival; Nomogram; Prognostic factors; Renal cell carcinoma; Scoring algorithms

Indexed keywords

ALGORITHM; CANCER STAGING; DISEASE COURSE; HUMAN; KIDNEY CARCINOMA; KIDNEY TUMOR; PATHOLOGY; PROGNOSIS; REVIEW;

ALGORITHMS; CARCINOMA, RENAL CELL; DISEASE PROGRESSION; HUMANS; KIDNEY NEOPLASMS; NEOPLASM STAGING; PROGNOSIS;

EID: 42349109579     PISSN: 07244983     EISSN: 14338726     Source Type: Journal    
DOI: 10.1007/s00345-008-0259-y     Document Type: Review

References (84)

1. Lam JS, Pantuck AJ, Belldegrun AS, Figlin RA (2007) Protein expression profiles in renal cell carcinoma: Staging, prognosis, and patient selection for clinical trials. Clin Cancer Res 15;13(2 Pt 2):703s-708s
2. Kattan MW, Reuter V, Motzer RJ, Katz J, Russo P (2001) A postoperative prognostic nomogram for renal cell carcinoma. J Urol 166(1):63-67
3. Zisman A, Pantuck AJ, Dorey F, Chao DH, Gitlitz BJ, Moldawer N, Lazarovici D, deKernion JB, Figlin RA, Belldegrun AS (2002) Mathematical model to predict individual survival for patients with renal cell carcinoma. J Clin Oncol 20(5):1368-1374
4. Motzer RJ, Bacik J, Murphy BA, Russo P, Mazumdar M (2002) Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol 20(1):289-296
5. Frank I, Blute ML, Cheville JC, Lohse CM, Weaver AL, Zincke H (2002) An outcome prediction model for patients with clear cell renal cell carcinoma treated with radical nephrectomy based on tumor stage, size, grade and necrosis: The SSIGN score. J Urol 168(6):2395-2400
6. Sorbellini M, Kattan MW, Snyder ME, Reuter V, Motzer R, Goetzl M, McKiernan J, Russo P (2005) A postoperative prognostic nomogram predicting recurrence for patients with conventional clear cell renal cell carcinoma. J Urol 173(1):48-51
7. Karakiewicz PI, Briganti A, Chun FK, Trinh QD, Perrotte P, Ficarra V, Cindolo L, De la Taille A, Tostain J, Mulders PF, Salomon L, Zigeuner R, Prayer-Galetti T, Chautard D, Valeri A, Lechevallier E, Descotes JL, Lang H, Mejean A, Patard JJ (2007) Multi-institutional validation of a new renal cancer-specific survival nomogram. J Clin Oncol 25(11):1316-1322
8. Yap TA, Eisen TG (2006) Adjuvant therapy of renal cell carcinoma. Clin Genitourin Cancer 5(2):120-130
9. Bellmunt J, Montagut C, Albiol S, Carles J, Maroto P, Orsola A (2007) Present strategies in the treatment of metastatic renal cell carcinoma: an update on molecular targeting agents. BJU Int 99(2):274-280
10. Hafez KS, Fergany AF, Novick AC (1999) Nephron sparing surgery for localized renal cell carcinoma: Impact of tumor size on patient survival, tumor recurrence and TNM staging. J Urol 162(6):1930-1933
11. Zisman A, Pantuck AJ, Chao D, Dorey F, Said JW, Gitlitz BJ, de Kernion JB, Figlin RA, Belldegrun AS (2001) Reevaluation of the 1997 TNM classification for renal cell carcinoma: T1 and T2 cutoff point at 4.5 rather than 7 cm. better correlates with clinical outcome. J Urol 166(1):54-58
12. Frank I, Blute ML, Leibovich BC, Cheville JC, Lohse CM, Zincke H (2005) Independent validation of the 2002 American Joint Committee on cancer primary tumor classification for renal cell carcinoma using a large, single institution cohort. J Urol 173(6):1889-1892
13. Motzer RJ, Bacik J, Schwartz LH, Reuter V, Russo P, Marion S, Mazumdar M (2004) Prognostic factors for survival in previously treated patients with metastatic renal cell carcinoma. J Clin Oncol 22(3):454-463
14. Ficarra V, Schips L, Guille F, Li G, De La Taille A, Prayer Galetti T, Cindolo L, Novara G, Zigeuner RE, Bratti E, Tostain J, Altieri V, Abbou CC, Artibani W, Patard JJ (2005) Multiinstitutional European validation of the 2002 TNM staging system in conventional and papillary localized renal cell carcinoma. Cancer 104(5):968-974
15. Ficarra V, Galfano A, Guille F, Schips L, Tostain J, Mejean A, Lang H, Mulders P, De La Taille A, Chautard D, Descotes JL, Cindolo L, Novara G, Rioux-Leclercq N, Zattoni F, Artibani W, Patard JJ (2007) A new staging system for locally advanced (pT3-4) renal cell carcinoma: A multicenter European study including 2,000 patients. J Urol 178(2):418-424
16. Karakiewicz PI, Trinh QD, Bhojani N, Bensalah K, Salomon L, de la Taille A, Tostain J, Cindolo L, Altieri V, Ficarra V, Schips L, Zigeuner R, Mulders PF, Valeri A, Descotes JL, Mejean A, Patard JJ (2007) Renal cell carcinoma with nodal metastases in the absence of distant metastatic disease: Prognostic indicators of disease-specific survival. Eur Urol 51(6):1616-1624
17. Ficarra V, Galfano A, Mancini M, Martignoni G, Artibani W (2007) TNM staging system for renal-cell carcinoma: Current status and future perspectives. Lancet Oncol 8(6):554-558
18. Ficarra V, Novara G, Galfano A, Artibani W (2004) Neoplasm staging and organ-confined renal cell carcinoma: A systematic review. Eur Urol 46(5):559-564
19. Ficarra V, Guille F, Schips L, de la Taille A, Prayer Galetti T, Tostain J, Cindolo L, Novara G, Zigeuner R, Bratti E, Li G, Altieri V, Abbou CC, Zanolla L, Artibani W, Patard JJ (2005) Proposal for revision of the TNM classification system for renal cell carcinoma. Cancer 104(10):2116-2123
20. Frank I, Blute ML, Leibovich BC, Cheville JC, Lohse CM, Kwon ED, Zincke H (2005) pT2 classification for renal cell carcinoma. Can its accuracy be improved? J Urol 173(2):380-384
21. Klatte T, Patard JJ, Goel RH, Kleid MD, Guille F, Lobel B, Abbou CC, De La Taille A, Tostain J, Cindolo L, Altieri V, Ficarra V, Artibani W, Prayer-Galetti T, Allhoff EP, Schips L, Zigeuner R, Figlin RA, Kabbinavar FF, Pantuck AJ, Belldegrun AS, Lam JS (2007) Prognostic impact of tumor size on pT2 renal cell carcinoma: An international multicenter experience. J Urol 178(1):35-40
22. Greene FL, Page D, Fleming ID et al (eds) (2002) AJCC cancer staging manual, 6th edn. Springer, New York
23. Thompson RH, Cheville JC, Lohse CM, Webster WS, Zincke H, Kwon ED, Frank I, Blute ML, Leibovich BC (2005) Reclassification of patients with pT3 and pT4 renal cell carcinoma improves prognostic accuracy. Cancer 104(1):53-60
24. Patard JJ, Rioux-leclercq N, Cindolo L, Ficarra V, Bensalah K, De La Taille A, Salomon L, Abbou CC, Tostain J, Lobel B, Guille F (2006) Prognostic value of urinary collecting system invasion in renal cell carcinoma. Eur Urol Suppl 5(2):67
25. Lohse CM, Cheville JC (2005) A review of prognostic pathologic features and algorithms for patients treated surgically for renal cell carcinoma. Clin Lab Med 25(2):433-464
26. Terrone C, Cracco C, Porpiglia F, Bollito E, Scoffone C, Poggio M, Berruti A, Ragni F, Cossu M, Scarpa RM, Rossetti SR (2006) Reassessing the current TNM lymph node staging for renal cell carcinoma. Eur Urol 49(2):324-331
27. Dimashkieh HH, Lohse CM, Blute ML, Kwon ED, Leibovich BC, Cheville JC (2006) Extranodal extension in regional lymph nodes is associated with outcome in patients with renal cell carcinoma. J Urol 176(5):1978-1982
28. Vasselli JR, Yang JC, Linehan WM, White DE, Rosenberg SA, Walther MM (2001) Lack of retroperitoneal lymphadenopathy predicts survival of patients with metastatic renal cell carcinoma. J Urol 166(1):68-72
29. Pantuck AJ, Zisman A, Dorey F, Chao DH, Han KR, Said J, Gitlitz BJ, Figlin RA, Belldegrun AS (2003) Renal cell carcinoma with retroperitoneal lymph nodes: Role of lymph node dissection. J Urol 169(6):2076-2083
30. Patard JJ, Kim HL, Lam JS, Dorey FJ, Pantuck AJ, Zisman A, Ficarra V, Han KR, Cindolo L, De La Taille A, Tostain J, Artibani W, Dinney CP, Wood CG, Swanson DA, Abbou CC, Lobel B, Mulders PF, Chopin DK, Figlin RA, Belldegrun AS (2004) Use of the University of California Los Angeles integrated staging system to predict survival in renal cell carcinoma: an international multicenter study. J Clin Oncol 22(16):3316-3322
31. Karakiewicz PI, Trinh QD, de la Taille A, Abbou CC, Salomon L, Tostain J, Cindolo L, Artibani W, Ficarra V, Patard JJ (2007) ECOG performance status 0 or 1 and symptom classification do not improve the ability to predict renal cell carcinoma-specific survival. Eur J Cancer 43(6):1023-1029
32. Ficarra V, Prayer-Galetti T, Novella G, Bratti E, Maffei N, Dal Bianco M, Artibani W, Pagano F (2003) Incidental detection beyond pathological factors as prognostic predictor of renal cell carcinoma. Eur Urol 43(6):663-669
33. Patard JJ, Dorey FJ, Cindolo L, Ficarra V, De La Taille A, Tostain J, Artibani W, Abbou CC, Lobel B, Chopin DK, Figlin RA, Belldegrun AS, Pantuck AJ (2004) Symptoms as well as tumor size provide prognostic information on patients with localized renal tumors. J Urol 172(6 Pt 1):2167-2171
34. Sengupta S, Lohse CM, Cheville JC, Leibovich BC, Thompson RH, Webster WS, Frank I, Zincke H, Blute ML, Kwon ED (2006) The preoperative erythrocyte sedimentation rate is an independent prognostic factor in renal cell carcinoma. Cancer 106(2):304-312
35. Bensalah K, Leray E, Fergelot P, Rioux-Leclercq N, Tostain J, Guillè F, Patard JJ (2006) Prognostic value of thrombocytosis in renal cell carcinoma. J Urol 175(3 Pt 1):859-863
36. Cheville JC, Lohse CM, Zincke H, Weaver AL, Blute ML (2003) Comparisons of outcome and prognostic features among histologic subtypes of renal cell carcinoma. Am J Surg Pathol 27(5):612-624
37. Patard JJ, Leray E, Rioux-Leclercq N, Cindolo L, Ficarra V, Zisman A, De La Taille A, Tostain J, Artibani W, Abbou CC, Lobel B, Guille F, Chopin DK, Mulders PF, Wood CG, Swanson DA, Figlin RA, Belldegrun AS, Pantuck AJ (2005) Prognostic value of histologic subtypes in renal cell carcinoma: A multicenter experience. J Clin Oncol 23(12):2763-2771
38. Ficarra V, Martignoni G, Galfano A, Novara G, Gobbo S, Brunelli M, Pea M, Zattoni F, Artibani W (2006) Prognostic role of the histologic subtypes of renal cell carcinoma after slide revision. Eur Urol 50(4):786-793
39. Storkel S, Eble JN, Adlakha K, Amin M, Blute ML, Bostwick DG, Darson M, Delahunt B, Iczkowski K (1997) Classification of renal cell carcinoma: Workgroup No. 1. Union Internationale Contre le Cancer (UICC) and the American Joint Committee on Cancer (AJCC). Cancer 80(5):987-989
40. Fuhrman SA, Lasky LC, Limas C (1982) Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol 6:655-663
41. Novara G, Martignoni G, Artibani W, Ficarra V (2007) Grading systems in renal cell carcinoma. J Urol 177(2):430-436
42. Rioux-Leclercq N, Karakiewicz PI, Trinh QD, Ficarra V, Cindolo L, de la Taille A, Tostain J, Zigeuner R, Mejean A, Patard JJ (2007) Prognostic ability of simplified nuclear grading of renal cell carcinoma. Cancer 109(5):868-874
43. Ficarra V, Martignoni G, Maffei N, Brunelli M, Novara G, Zanolla L, Pea M, Artibani W (2005) Original and reviewed nuclear grading according to the Fuhrman system: A multivariate analysis of 388 patients with conventional renal cell carcinoma. Cancer 103(1):68-75
44. Mejean A, Hopirtean V, Bazin JP, Larousserie F, Benoit H, Chretien Y, Thiounn N, Dufour B (2003) Prognostic factors for the survival of patients with papillary renal cell carcinoma: Meaning of histological typing and multifocality. J Urol 170(3):764-767
45. Sika-Paotonu D, Bethwaite PB, McCredie MR, William Jordan T, Delahunt B (2006) Nucleolar grade but not Fuhrman grade is applicable to papillary renal cell carcinoma. Am J Surg Pathol 30(9):1091-1096
46. Delahunt B, Sika-Paotonu D, Bethwaite PB, McCredie MR, Martignoni G, Eble JN, Jordan TW (2007) Fuhrman grading is not appropriate for chromophobe renal cell carcinoma. Am J Surg Pathol 31(6):957-960
47. Sengupta S, Lohse CM, Leibovich BC, Frank I, Thompson RH, Webster WS, Zincke H, Blute ML, Cheville JC, Kwon ED (2005) Histologic coagulative tumor necrosis as a prognostic indicator of renal cell carcinoma aggressiveness. Cancer 104(3):511-520
48. de Peralta-Venturina M, Moch H, Amin M, Tamboli P, Hailemariam S, Mihatsch M, Javidan J, Stricker H, Ro JY, Amin MB (2001) Sarcomatoid differentiation in renal cell carcinoma: A study of 101 cases. Am J Surg Pathol 25(3):275-284
49. Wood CG (2006) Molecular markers of prognosis in renal cell carcinoma: insight into tumor biology helps define risk and provides targets for therapy. J Surg Oncol 4(4):264-265
50. Lam JS, Leppert JT, Figlin RA, Belldegrun AS (2005) Role of molecular markers in the diagnosis and therapy of renal cell carcinoma. Urology 66(5 Suppl):1-9
51. Leppert JT, Lam JS, Pantuck AJ, Figlin RA, Belldegrun AS (2005) Carbonic anhydrase IX and the future of molecular markers in renal cell carcinoma. BJU Int 96(3):281-285
52. Bui MH, Seligson D, Han KR, Pantuck AJ, Dorey FJ, Huang Y, Horvath S, Leibovich BC, Chopra S, Liao SY, Stanbridge E, Lerman MI, Palotie A, Figlin RA, Belldegrun AS (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(2):802-811
53. Bui MH, Visapaa H, Seligson D, Kim H, Han KR, Huang Y, Horvath S, Stanbridge EJ, Palotie A, Figlin RA, Belldegrun AS (2004) Prognostic value of carbonic anhydrase IX and KI67 as predictors of survival for renal clear cell carcinoma. J Urol 171(6 Pt 1):2461-2466
54. Kim HL, Seligson D, Liu X, Janzen N, Bui MH, Yu H, Shi T, Belldegrun AS, Horvath S, Figlin RA (2005) Using tumor markers to predict the survival of patients with metastatic renal cell carcinoma. J Urol 173(5):1496-1501
55. Atkins M, Regan M, McDermott D, Mier J, Stanbridge E, Youmans A, Febbo P, Upton M, Lechpammer M, Signoretti S (2005) Carbonic anhydrase IX expression predicts outcome of interleukin 2 therapy for renal cancer. Clin Cancer Res 11(10):3714-3721
56. Leibovich B, Sheinin Y, Lohse CM, Thompson RH, Cheville JC, Zavada J, Kwon ED (2007) Carbonic anhydrase IX Is not an independent predictor of outcome for patients with clear cell renal cell carcinoma. J Clin Oncol 25:4757-4764
57. Thompson RH, Gillett MD, Cheville JC, Lohse CM, Dong H, Webster WS, Krejci KG, Lobo JR, Sengupta S, Chen L, Zincke H, Blute ML, Strome SE, Leibovich BC, Kwon ED (2004) Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target. Proc Natl Acad Sci USA 101(49):17174-17179
58. Thompson RH, Gillett MD, Cheville JC, Lohse CM, Dong H, Webster WS, Chen L, Zincke H, Blute ML, Leibovich BC, Kwon ED (2005) Costimulatory molecule B7-H1 in primary and metastatic clear cell renal cell carcinoma. Cancer 104(10):2084-2091
59. Krambeck AE, Thompson RH, Dong H, Lohse CM, Park ES, Kuntz SM, Leibovich BC, Blute ML, Cheville JC, Kwon ED (2006) B7-H4 expression in renal cell carcinoma and tumor vasculature: Associations with cancer progression and survival. Proc Natl Acad Sci USA 103(27):10391-10396
60. Thompson RH, Kuntz SM, Leibovich BC, Dong H, Lohse CM, Webster WS, Sengupta S, Frank I, Parker AS, Zincke H, Blute ML, Sebo TJ, Cheville JC, Kwon ED (2006) Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up. Cancer Res 66(7):3381-3385
61. Krambeck AE, Dong H, Thompson RH, Kuntz SM, Lohse CM, Leibovich BC, Blute ML, Sebo TJ, Cheville JC, Parker AS, Kwon ED (2007) Survivin and b7-h1 are collaborative predictors of survival and represent potential therapeutic targets for patients with renal cell carcinoma. Clin Cancer Res 13(6):1749-1756
62. Kopper L, Timar J (2006) Genomics of renal cell cancer - does it provide breakthrough? Pathol Oncol Res 12(1):5-11
63. Brunelli M, Eccher A, Gobbo S, Ficarra V, Novara G, Cossu-Rocca P, Bonetti F, Menestrina F, Cheng L, Eble JN, Martignoni G (2008) Loss of chromosome 9p is an independent prognostic factor in patients with clear cell renal cell carcinoma. Mod Pathol (in press)
64. Frey UH, Lummen G, Jager T, Jockel KH, Schmid KW, Rubben H, Muller N, Siffert W, Eisenhardt A (2006) The GNAS1 T393C polymorphism predicts survival in patients with clear cell renal cell carcinoma. Clin Cancer Res 12(3 Pt 1):759-763
65. Ito N, Eto M, Nakamura E, Takahashi A, Tsukamoto T, Toma H, Nakazawa H, Hirao Y, Uemura H, Kagawa S, Kanayama H, Nose Y, Kinukawa N, Nakamura T, Jinnai N, Seki T, Takamatsu M, Masui Y, Naito S, Ogawa O (2007) STAT3 polymorphism predicts interferon-alfa response in patients with metastatic renal cell carcinoma. J Clin Oncol 25(19):2785-2791
66. Leppert JT, Pantuck AJ, Figlin RA, Belldegrun AS (2007) The role of molecular markers in the staging of renal cell carcinoma. BJU Int 99(5 Pt B):1208-1211
67. Yaycioglu O, Roberts WW, Chan T, Epstein JI, Marshall FF, Kavoussi LR (2001) Prognostic assessment of nonmetastatic renal cell carcinoma: A clinically based model. Urology 58(2):141-145
68. Zisman A, Pantuck AJ, Dorey F, Said JW, Shvarts O, Quintana D, Gitlitz BJ, deKernion JB, Figlin RA, Belldegrun AS (2001) Improved prognostication of renal cell carcinoma using an integrated staging system. J Clin Oncol 19(6):1649-1657
69. Cindolo L, de la Taille A, Messina G, Romis L, Abbou CC, Altieri V, Rodriguez A, Patard JJ (2003) A preoperative clinical prognostic model for non-metastatic renal cell carcinoma. BJU Int 92(9):901-905
70. Leibovich BC, Blute ML, Cheville JC, Lohse CM, Frank I, Kwon ED, Weaver AL, Parker AS, Zincke H (2003) Prediction of progression after radical nephrectomy for patients with clear cell renal cell carcinoma: A stratification tool for prospective clinical trials. Cancer 97(7):1663-1671
71. Leibovich BC, Cheville JC, Lohse CM, Zincke H, Frank I, Kwon ED, Merchan JR, Blute ML (2005) A scoring algorithm to predict survival for patients with metastatic clear cell renal cell carcinoma: A stratification tool for prospective clinical trials. J Urol 174(5):1759-1763
72. Cindolo L, Patard JJ, Chiodini P, Schips L, Ficarra V, Tostain J, de La Taille A, Altieri V, Lobel B, Zigeuner RE, Artibani W, Guille F, Abbou CC, Salzano L, Gallo C (2005) Comparison of predictive accuracy of four prognostic models for nonmetastatic renal cell carcinoma after nephrectomy: A multicenter European study. Cancer 104(7):1362-1371
73. Hupertan V, Roupret M, Poisson JF, Chretien Y, Dufour B, Thiounn N, Mejean A (2006) Low predictive accuracy of the Kattan postoperative nomogram for renal cell carcinoma recurrence in a population of French patients. Cancer 107(11):2604-2608
74. Han KR, Bleumer I, Pantuck AJ, Kim HL, Dorey FJ, Janzen NK, Zisman A, Dinney CP, Wood CG, Swanson DA, Said JW, Figlin RA, Mulders PF, Belldegrun AS (2003) Validation of an integrated staging system toward improved prognostication of patients with localized renal cell carcinoma in an international population. J Urol 170(6 Pt 1):2221-2224
75. Ficarra V, Martignoni G, Lohse C, Novara G, Pea M, Cavalleri S, Artibani W (2006) External validation of the Mayo clinic stage, size, grade and necrosis (SSIGN) score to predict cancer specific survival using a European series of conventional renal cell carcinoma. J Urol 175(4):1235-1239
76. Thompson RH, Leibovich BC, Lohse CM, Cheville JC, Zincke H, Blute ML, Frank I (2007) Dynamic outcome prediction in patients with clear cell renal cell carcinoma treated with radical nephrectomy: The D-SSIGN score. J Urol 177(2):477-480
77. Eggener SE, Yossepowitch O, Pettus JA, Snyder ME, Motzer RJ, Russo P (2006) Renal cell carcinoma recurrence after nephrectomy for localized disease: Predicting survival from time of recurrence. J Clin Oncol 24(19):3101-3106
78. Messing EM, Manola J, Wilding G, Propert K, Fleischmann J, Crawford ED, Pontes JE, Hahn R, Trump D, Eastern Cooperative Oncology Group/ Intergroup trial (2003) Phase III study of interferon alfa-NL as adjuvant treatment for resectable renal cell carcinoma: An Eastern Cooperative Oncology Group/Intergroup trial. J Clin Oncol 21(7):1214-1222
79. Rini BI, Halabi S, Taylor J, Small EJ, Schilsky RL, Cancer, Leukemia Group B (2004) Cancer and leukemia group B 90206: A randomized phase III trial of interferon-alpha or interferon-alpha plus anti-vascular endothelial growth factor antibody (bevacizumab) in metastatic renal cell carcinoma. Clin Cancer Res 10(8):2584-2586
80. Donskov F, Middleton M, Fode K, Meldgaard P, Mansoor W, Lawrance J, Thatcher N, Nellemann H, von der Maase H (2005) Two randomised phase II trials of subcutaneous interleukin-2 and histamine dihydrochloride in patients with metastatic renal cell carcinoma. Br J Cancer 93(7):757-762
81. Atkins MB, Hidalgo M, Stadler WM, Logan TF, Dutcher JP, Hudes GR, Park Y, Liou SH, Marshall B, Boni JP, Dukart G, Sherman ML (2004) Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma. J Clin Oncol 22(5):909-918
82. 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, TARGET Study Group (2007) Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356(2):125-134
83. 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 (2007) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356(2):115-124
84. Ratain MJ, Eisen T, Stadler WM, Flaherty KT, Kaye SB, Rosner GL, Gore M, Desai AA, Patnaik A, Xiong HQ, Rowinsky E, Abbruzzese JL, Xia C, Simantov R, Schwartz B, O'Dwyer PJ (2006) Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol 24(16):2505-252