Drugs & Aging

, Volume 28, Issue 8, pp 635–649

Systemic Therapies for Metastatic Renal Cell Carcinoma in Older Adults

  • Sumanta K. Pal
  • Ari Vanderwalde
  • Arti Hurria
  • Robert A. Figlin
Review Article

Abstract

The introduction of targeted therapies has radically changed the treatment paradigm for metastatic renal cell carcinoma (mRCC). However, multiple clinical dilemmas have emerged. For instance, limited data are available to juxtapose the safety and efficacy profile of targeted therapies between older and younger adults. Herein, pivotal trials of vascular endothelial growth factor (VEGF)- and mammalian target of rapamycin (mTOR)-directed therapies are assessed in the context of their implications in treating older adults with mRCC. In general, subset analyses from these pivotal studies suggest similar efficacy of targeted therapies amongst older adults. Aging is accompanied by a multitude of physiological changes, as well as an increased prevalence of co-morbidities. The age-related toxicity profiles of targeted agents for mRCC are detailed to provide a framework for the risks and benefits of these therapies in older adults. Ultimately, tools such as the Comprehensive Geriatric Assessment (CGA) that account for physiological (as opposed to chronological) age may prove useful in the evaluation and treatment of older adults with mRCC.

References

  1. 1.
    National Comprehensive Cancer Network. Clinical practice guidelines: renal cell carcinoma [online]. Available from URL: http://www.nccn.org [Accessed 2009 Nov 29]
  2. 2.
    Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007; 356: 115–24PubMedCrossRefGoogle Scholar
  3. 3.
    Sternberg CN, Davis ID, Mardiak J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 2010; 28: 1061–8PubMedCrossRefGoogle Scholar
  4. 4.
    Rini BI, Halabi S, Rosenberg JE, et al. Phase III trial of bevacizumab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic renal cell carcinoma: final results of CALGB 90206. J Clin Oncol 2010; 28: 2137–43PubMedCrossRefGoogle Scholar
  5. 5.
    Escudier B, Bellmunt J, Negrier S, et al. Phase III trial of bevacizumab plus interferon alfa-2a in patients with me-tastatic renal cell carcinoma (AVOREN): final analysis of overall survival. J Clin Oncol 2010; 28: 2144–50PubMedCrossRefGoogle Scholar
  6. 6.
    Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007; 356: 125–34PubMedCrossRefGoogle Scholar
  7. 7.
    Motzer RJ, Escudier B, Oudard S, et al. Efficacy of ever-olimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 2008; 372: 449–56PubMedCrossRefGoogle Scholar
  8. 8.
    Hudes G, Carducci M, Tomczak P, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 2007; 356: 2271–81PubMedCrossRefGoogle Scholar
  9. 9.
    Pal SK, Figlin RA. Renal cell carcinoma therapy in 2010: many options with little comparative data. Clin Adv He-matol Oncol 2010; 8: 191–200Google Scholar
  10. 10.
    Pal SK, Kortylewski M, Yu H, et al. Breaking through a plateau in renal cell carcinoma therapeutics: development and incorporation of biomarkers. Mol Cancer Ther 2010 Dec; 9(12): 3115–25PubMedCrossRefGoogle Scholar
  11. 11.
    Heng DYC, Xie W, Regan MM, et al. Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol 2009; 27: 5794–9PubMedCrossRefGoogle Scholar
  12. 12.
    Shayne M, Crawford J, Dale DC, et al. Predictors of reduced dose intensity in patients with early-stage breast cancer receiving adjuvant chemotherapy. Breast Cancer Res Treat 2006; 100: 255–62PubMedCrossRefGoogle Scholar
  13. 13.
    Safont MJ, Artal-Cortes A, Sirera R, et al. Retrospective study of efficacy and toxicity on patients older than 70 years within a randomized clinical trial oft wo cisplatin-based combinations in patients with small-cell lung cancer. Lung Cancer 2009; 63: 83–7PubMedCrossRefGoogle Scholar
  14. 14.
    Fader AN, von Gruenigen V, Gibbons H, et al. Improved tolerance of primary chemotherapy with reduced-dose carboplatin and paclitaxel in elderly ovarian cancer patients. Gynecol Oncol 2008; 109: 33–8PubMedCrossRefGoogle Scholar
  15. 15.
    Latagliata R, Breccia M, Carmosino I, et al. ‘Real-life’ results of front-line treatment with imatinib in older patients (≥65 years) with newly diagnosed chronic myelogenous leukemia. Leuk Res 2010; 34: 1472–5PubMedCrossRefGoogle Scholar
  16. 16.
    Palumbo A, Gay F. How to treat elderly patients with multiple myeloma: combination of therapy or sequencing. Hematol Am Soc Hematol Educ Program 2009: 566–77Google Scholar
  17. 17.
    Shayne M, Culakova E, Poniewierski MS, et al. Dose intensity and hematologic toxicity in older cancer patients receiving systemic chemotherapy. Cancer 2007; 110: 1611–20PubMedCrossRefGoogle Scholar
  18. 18.
    Lyman GH, Dale DC, Friedberg J, et al. Incidence and predictors of low chemotherapy dose-intensity in aggressive non-Hodgkin’s lymphoma: a nationwide study. J Clin Oncol 2004; 22: 4302–11PubMedCrossRefGoogle Scholar
  19. 19.
    Kondo K, Yao M, Yoshida M, et al. Comprehensive mutational analysis of the VHL gene in sporadic renal cell carcinoma: relationship to clinicopathological parameters. Genes Chromosomes Cancer 2002; 34: 58–68PubMedCrossRefGoogle Scholar
  20. 20.
    Rodriguez A, Patard JJ, Lobel B. Renal cell carcinoma in young adults: incidence, disease outcome and review of the literature. Arch Esp Urol 2002; 55: 969–75PubMedGoogle Scholar
  21. 21.
    Gillett MD, Cheville JC, Karnes RJ, et al. Comparison of presentation and outcome for patients 18 to 40 and 60 to 70 years old with solid renal masses. J Urol 2005; 173: 1893–6PubMedCrossRefGoogle Scholar
  22. 22.
    Cao Y, Paner GP, Perry KT, et al. Renal neoplasms in younger adults: analysis of 112 tumors from a single institution according to the new 2004 World Health Organization classification and 2002 American Joint Committee on Cancer Staging System. Arch Pathol Lab Med 2005; 129: 487–91PubMedGoogle Scholar
  23. 23.
    Bruder E, Passera O, Harms D, et al. Morphologic and molecular characterization of renal cell carcinoma in children and young adults. Am J Surg Pathol 2004; 28: 1117–32PubMedCrossRefGoogle Scholar
  24. 24.
    Renshaw AA, Granter SR, Fletcher JA, et al. Renal cell carcinomas in children and young adults: increased incidence ofpapillary architecture and unique subtypes. Am J Surg Pathol 1999; 23: 795–802PubMedCrossRefGoogle Scholar
  25. 25.
    Rainwater LM, Zincke H, Farrow GM, et al. Renal cell carcinoma in young and old patients: comparison of prognostic pathologic variables (cell type, tumor grade and stage, and DNA ploidy pattern) and their impact on disease outcome. Urology 1991; 38: 1–5PubMedCrossRefGoogle Scholar
  26. 26.
    Abou El Fettouh HI, Cherullo EE, El-Jack M, et al. Sporadic renal cell carcinoma in young adults: presentation, treatment, and outcome. Urology 2002; 60: 806–10PubMedCrossRefGoogle Scholar
  27. 27.
    Thompson RH, Ordonez MA, Iasonos A, et al. Renal cell carcinoma in young and old patients: is there a difference? J Urol 2008; 180: 1262–6PubMedCrossRefGoogle Scholar
  28. 28.
    Townsley CA, Pond GR, Oza AM, et al. Evaluation of adverse events experienced by older patients participating in studies of molecularly targeted agents alone or in combination. Clin Cancer Res 2006; 12: 2141–9PubMedCrossRefGoogle Scholar
  29. 29.
    Kantarjian H, Sawyers C, Hochhaus A, et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med 2002; 346: 645–52PubMedCrossRefGoogle Scholar
  30. 30.
    Heinrich MC, Corless CL, Demetri GD, et al. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol 2003; 21: 4342–9PubMedCrossRefGoogle Scholar
  31. 31.
    Baker S, van Schaik R, Rivory L, et al. Factors affecting cytochrome P-450 activity in cancer patients. Clin Cancer Res 2004; 10: 8341–50PubMedCrossRefGoogle Scholar
  32. 32.
    Sotaniemi EA, Arranto AJ, Pelkonen O, et al. Age and cytochrome P450-linked drug metabolism in humans: an analysis of 226 subjects with equal histopathologic conditions. Clin Pharmacol Ther 1997; 61: 331–9PubMedCrossRefGoogle Scholar
  33. 33.
    Sawhney R, Sehl M, Naeim A. Physiologic aspects of aging: impact on cancer management and decision making, part I. Cancer J 2005; 11: 449–60PubMedCrossRefGoogle Scholar
  34. 34.
    Vestal RE. Aging and pharmacology. Cancer 1997; 80: 1302–10PubMedCrossRefGoogle Scholar
  35. 35.
    Go RS, Adjei AA. Review of the comparative pharmacology and clinical activity of cisplatin and carboplatin [letter]. J Clin Oncol 1999; 17: 409PubMedGoogle Scholar
  36. 36.
    Toffoli G, Corona G, Sorio R, et al. Population phar-macokinetics and pharmacodynamics of oral etoposide. Br J Clin Pharmacol 2001; 52: 511–9PubMedCrossRefGoogle Scholar
  37. 37.
    Yuen GJ. Altered pharmacokinetics in the elderly. Clin Geriatr Med 1990; 6: 257–67PubMedGoogle Scholar
  38. 38.
    Baker SD, Grochow LB. Pharmacology of cancer chemotherapy in the older person. Clin Geriatr Med 1997; 13: 169–83PubMedGoogle Scholar
  39. 39.
    Ando M, Minami H, Ando Y, et al. Pharmacological analysis of etoposide in elderly patients with lung cancer. Clin Cancer Res 1999; 5: 1690–5PubMedGoogle Scholar
  40. 40.
    Fidias P, Supko JG, Martins R, et al. A phase II study of weekly paclitaxel in elderly patients with advanced non-small cell lung cancer. Clin Cancer Res 2001; 7: 3942–9PubMedGoogle Scholar
  41. 41.
    Gauvin A, Pinguet F, Culine S, et al. Bayesian estimate of vinorelbine pharmacokinetic parameters in elderly patients with advanced metastatic cancer. Clin Cancer Res 2000; 6: 2690–5PubMedGoogle Scholar
  42. 42.
    Hurria A, Fleming MT, Baker SD, et al. Pharmacokinetics and toxicity of weekly docetaxel in older patients. Clin Cancer Res 2006; 12: 6100–5PubMedCrossRefGoogle Scholar
  43. 43.
    Lichtman SM, Hollis D, Miller AA, et al. Prospective evaluation of the relationship of patient age and paclitaxel clinical pharmacology: cancer and leukemia group B (CALGB 9762). J Clin Oncol 2006; 24: 1846–51PubMedCrossRefGoogle Scholar
  44. 44.
    Sorio R, Robieux I, Galligioni E, et al. Pharmacokinetics and tolerance of vinorelbine in elderly patients with me-tastatic breast cancer. Eur J Cancer 1997; 33: 301–3PubMedCrossRefGoogle Scholar
  45. 45.
    Yancik R, Ries LA. Aging and cancer in America: demographic and epidemiologic perspectives. Hematol Oncol Clin North Am 2000; 14: 17–23PubMedCrossRefGoogle Scholar
  46. 46.
    Keating NL, Landrum MB, Klabunde CN, et al. Adjuvant chemotherapy for stage III colon cancer: do physicians agree about the importance of patient age and comor-bidity? J Clin Oncol 2008; 26: 2532–7PubMedCrossRefGoogle Scholar
  47. 47.
    Hurria A, Wong FL, Villaluna D, et al. Role of age and health in treatment recommendations for older adults with breast cancer: the perspective of oncologists and primary care providers. J Clin Oncol 2008; 26: 5386–92PubMedCrossRefGoogle Scholar
  48. 48.
    Blanco JAG, Toste IS, Alvarez RF, et al. Age, comorbidity, treatment decision and prognosis in lung cancer. Age Ageing 2008; 37: 715–8PubMedCrossRefGoogle Scholar
  49. 49.
    Chen HX, Cleck JN. Adverse effects of anticancer agents that target the VEGF pathway. Nat Rev Clin Oncol 2009; 6: 465–77PubMedCrossRefGoogle Scholar
  50. 50.
    Rini BI, Cohen DP, Lu D, et al. Hypertension (HTN) as a biomarker of efficacy in patients (pts) with metastatic renal cell carcinoma (mRCC) treated with sunitinib [abstract no. 312]. Presented at the 2010 Genitourinary Cancers Symposium; 2010 Mar 5–7; San Francisco (CA)Google Scholar
  51. 51.
    Pal SK, Figlin RA. Treatment options in metastatic renal cell carcinoma: focus on mTOR inhibitors. Clin Med Insights Oncol 2010; 4: 43–53PubMedGoogle Scholar
  52. 52.
    Sokol KC, Knudsen JF, Li MM. Polypharmacy in older oncology patients and the need for an interdisciplinary approach to side-effect management. J Clin Pharm Ther 2007; 32: 169–75PubMedCrossRefGoogle Scholar
  53. 53.
    Maggiore RJ, Gross CP, Hurria A. Polypharmacy in older adults with cancer. Oncologist 2010; 15: 507–22PubMedCrossRefGoogle Scholar
  54. 54.
    Flood KL, Carroll MB, Le CV, et al. Polypharmacy in hospitalized older adult cancer patients: experience from a prospective, observational study of an oncology-acute care for elders unit. Am J Geriatr Pharmacother 2009; 7: 151–8PubMedCrossRefGoogle Scholar
  55. 55.
    Corcoran ME. Polypharmacy in the older patient with cancer. Cancer Control 1997; 4: 419–28PubMedGoogle Scholar
  56. 56.
    US FDA. Approval letter for sorafenib [online]. Available from URL: http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2005/021923ltr.pdf [Accessed 2010 Mar 24]
  57. 57.
    Eisen T, Oudard S, Szczylik C, et al. Sorafenib for older patients with renal cell carcinoma: subset analysis from a randomized trial. J Natl Cancer Inst 2008; 100: 1454–63PubMedCrossRefGoogle Scholar
  58. 58.
    Bukowski RM, Stadler WM, McDermott DF, et al. Safety and efficacy of sorafenib in elderly patients treated in the North American advanced renal cell carcinoma sorafenib expanded access program. Oncology 2010; 78: 340–7PubMedCrossRefGoogle Scholar
  59. 59.
    Motzer RJ, Hutson TE, Tomczak P, et al. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol 2009; 27: 3584–90PubMedCrossRefGoogle Scholar
  60. 60.
    Gore ME, Porta C, Oudard S, et al. Sunitinib in metastatic renal cell carcinoma (mRCC): preliminary assessment of toxicity in an expanded access trial with subpopulation analysis. ASCO Meet Abstr 2007; 25: 5010Google Scholar
  61. 61.
    Rini BI, Halabi S, Rosenberg JE, et al. Bevacizumab plus interferon alfa compared with interferon alfa mono-therapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol 2008; 26: 5422–8PubMedCrossRefGoogle Scholar
  62. 62.
    Escudier B, Pluzanska A, Koralewski P, et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet 2007; 370: 2103–11PubMedCrossRefGoogle Scholar
  63. 63.
    Hutson TE, Osanto S, Calvo E, et al. Efficacy and safety of everolimus in elderly patients with metastatic renal cell carcinoma (mRCC) after disease progression on VEGFr-TKI therapy [abstract no. 11]. Presented at the 2010 Kidney Cancer Symposium; 2010 Oct 2; Chicago (IL)Google Scholar
  64. 64.
    Dutcher JP, Szczylik C, Tannir N, et al. Correlation of survival with tumor histology, age, and prognostic risk group for previously untreated patients with advanced renal cell carcinoma (adv RCC) receiving temsirolimus (TEMSR) or interferon-alpha (IFN). J Clin Oncol (Meet Abstr) 2007; 25: 5033Google Scholar
  65. 65.
    Dutcher JP, Szczylik C, Tannir N, et al. Correlation of survival with tumor histology, age, and prognostic risk group for previously untreated patients with advanced renal cell carcinoma (adv RCC) receiving temsirolimus (TEMSR) or interferon-alpha (IFN). ASCO Meet Abstr 2007; 25: 5033Google Scholar
  66. 66.
    McDermott DF, Ghebremichael MS, Signoretti S, et al. The high-dose aldesleukin (HD IL-2) ‘SELECT’ trial in patients with metastatic renal cell carcinoma (mRCC). J Clin Oncol (Meet Abst) 2010; 28: 4514Google Scholar
  67. 67.
    Fyfe G, Fisher RI, Rosenberg SA, et al. Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol 1995; 13: 688–96PubMedGoogle Scholar
  68. 68.
    Atzpodien J, Wandert T, Reitz M. Age does not impair the efficacy of immunochemotherapy in patients with meta-static renal carcinoma. Crit Rev Oncol/Hematol 2005; 55: 193–9CrossRefGoogle Scholar
  69. 69.
    Prout Jr GR, Wesley MN, Yancik R, et al. Age and co-morbidity impact surgical therapy in older bladder carcinoma patients: a population-based study. Cancer 2005; 104: 1638–47PubMedCrossRefGoogle Scholar
  70. 70.
    Shariat SF, Sfakianos JP, Droller MJ, et al. The effect of age and gender on bladder cancer: a critical review of the literature. Br J Urol Int 2009; 105: 300–8CrossRefGoogle Scholar
  71. 71.
    Mettlin CJ, Murphy GP, Cunningham MP, et al. The National Cancer Data Base report on race, age, and region variations inprostate cancer treatment. Cancer 1997; 80: 1261–6PubMedCrossRefGoogle Scholar
  72. 72.
    Lichtman SM, Wildiers H, Chatelut E, et al. International Society of Geriatric Oncology Chemotherapy Taskforce: evaluation of chemotherapy in older patients - an analysis of the medical literature. J Clin Oncol 2007; 25: 1832–43PubMedCrossRefGoogle Scholar
  73. 73.
    Talarico L, Chen G, Pazdur R. Enrollment of elderly patients in clinical trials for cancer drug registration: a 7-year experience by the US food and drug administration. J Clin Oncol 2004; 22: 4626–31PubMedCrossRefGoogle Scholar
  74. 74.
    Droz JP, Aapro M, Balducci L. Overcoming challenges associated with chemotherapy treatment in the senior adult population. Crit Rev Oncol Hematol 2008; 68Suppl. 1: S1–8PubMedCrossRefGoogle Scholar
  75. 75.
    Extermann M, Albrand G, Chen H, et al. Are older French patients as willing as older American patients to undertake chemotherapy? J Clin Oncol 2003; 21: 3214–9PubMedCrossRefGoogle Scholar
  76. 76.
    DeMichele A, Putt M, Zhang Y, et al. Older age predicts a decline in adjuvant chemotherapy recommendations for patients with breast carcinoma: evidence from a tertiary care cohort of chemotherapy-eligible patients. Cancer 2003; 97: 2150–9PubMedCrossRefGoogle Scholar
  77. 77.
    Hall WH, Jani AB, Ryu JK, et al. The impact of age and comorbidity on survival outcomes and treatment patterns in prostate cancer. Prostate Cancer Prostatic Dis 2005; 8: 22–30PubMedCrossRefGoogle Scholar
  78. 78.
    Rao AV, Seo PH, Cohen HJ. Geriatric assessment and comorbidity. Semin Oncol 2004; 31: 149–59PubMedCrossRefGoogle Scholar
  79. 79.
    Stuck AE, Siu AL, Wieland GD, et al. Comprehensive geriatric assessment: a meta-analysis of controlled trials. Lancet 1993; 342: 1032–6PubMedCrossRefGoogle Scholar
  80. 80.
    Freyer G, Geay J, Touzet S, et al. Comprehensive geriatric assessment predicts tolerance to chemotherapy and survival in elderly patients with advanced ovarian carcinoma: a GINECO study. Ann Oncol 2005; 16: 1795–800PubMedCrossRefGoogle Scholar
  81. 81.
    Bernabei R, Venturiero V, Tarsitani P, et al. The comprehensive geriatric assessment: when, where, how. Crit Rev Oncol Hematol 2000; 33: 45–56PubMedCrossRefGoogle Scholar
  82. 82.
    Monfardini S, Ferrucci L, Fratino L, et al. Validation of a multidimensional evaluation scale for use in elderly cancer patients. Cancer 1996; 77: 395–401PubMedCrossRefGoogle Scholar
  83. 83.
    Hurria A, Gupta S, Zauderer M, et al. Developing a cancer-specific geriatric assessment: a feasibility study. Cancer 2005; 104: 1998–2005PubMedCrossRefGoogle Scholar
  84. 84.
    Tucci A, Ferrari S, Bottelli C, et al. A comprehensive geriatric assessment is more effective than clinical judgment to identify elderly diffuse large cell lymphoma patients who benefit from aggressive therapy. Cancer 2009; 115: 4547–53PubMedCrossRefGoogle Scholar
  85. 85.
    Hurria A, Togawa K, Mohile SG, et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective 500 patient multicenter study [abstract no. 9001]. J Clin Oncol 2010; 28 Suppl.: 15sGoogle Scholar
  86. 86.
    Extermann M, Boler I, Reich R, et al. The chemotherapy risk assessment sclae for high-age patients (CRASH) score: design and validation [abstract no. 9000]. J Clin Oncol 2010; 28 Suppl.: 15sGoogle Scholar
  87. 87.
    Extermann M, Aapro M, Bernabei R, et al. Use of comprehensive geriatric assessment in older cancer patients: recommendations from the task force on CGA of the International Society of Geriatric Oncology (SIOG). Crit Rev Oncol Hematol 2005; 55: 241–52PubMedCrossRefGoogle Scholar
  88. 88.
    Balducci L, Cohen HJ, Engstrom PF, et al. Senior adult oncology clinical practice guidelines in oncology. J Natl Compr Canc Netw 2005; 3: 572–90PubMedGoogle Scholar
  89. 89.
    Extermann M, Hurria A. Comprehensive geriatric assessment for older patients with cancer. J Clin Oncol 2007; 25: 1824–31PubMedCrossRefGoogle Scholar
  90. 90.
    Maione P, Perrone F, Gallo C, et al. Pretreatment quality of life and functional status assessment significantly predict survival of elderly patients with advanced non-small-cell lung cancer receiving chemotherapy: a prognostic analysis of the Multicenter Italian Lung Cancer in the Elderly Study. J Clin Oncol 2005; 23: 6865–72PubMedCrossRefGoogle Scholar
  91. 91.
    Piccirillo JF, Tierney RM, Costas I, et al. Prognostic importance of comorbidity in a hospital-based cancer registry. JAMA 2004; 291: 2441–7PubMedCrossRefGoogle Scholar
  92. 92.
    Frasci G, Lorusso V, Panza N, et al. Gemcitabine plus vi-norelbine versus vinorelbine alone in elderly patients with advanced non-small-cell lung cancer. J Clin Oncol 2000; 18: 2529–36PubMedGoogle Scholar
  93. 93.
    Pallis AG, Fortpied C, Wedding U, et al. EORTC elderly task force position paper: approach to the older cancer patient. Eur J Cancer 2010; 46: 1502–13PubMedCrossRefGoogle Scholar
  94. 94.
    Ranpura V, Pulipati B, Chu D, et al. Increased risk ofhigh-grade hypertension with bevacizumab in cancer patients: a meta-analysis. Am J Hypertens 2010; 23: 460–8PubMedCrossRefGoogle Scholar
  95. 95.
    Zhu X, Stergiopoulos K, Wu S. Risk of hypertension and renal dysfunction with an angiogenesis inhibitor sunitinib: systematic review and meta-analysis. Acta Oncol 2009; 48: 9–17PubMedCrossRefGoogle Scholar
  96. 96.
    Wu S, Chen JJ, Kudelka A, et al. Incidence and risk of hypertension with sorafenib in patients with cancer: a systematic review and meta-analysis. Lancet Oncol 2008; 9: 117–23PubMedCrossRefGoogle Scholar
  97. 97.
    Bellmunt J, Negrier S, Escudier B, et al. The medical treatment of metastatic renal cell cancer in the elderly: position paper of a SIOG Taskforce. Crit Rev Oncol Hematol 2009; 69: 64–72PubMedCrossRefGoogle Scholar
  98. 98.
    Girardi F, Franceschi E, Brandes AA. Cardiovascular safety of VEGF-targeting therapies: current evidence and handling strategies. Oncologist 2010; 15: 683–94PubMedCrossRefGoogle Scholar
  99. 99.
    Scappaticci FA, Skillings JR, Holden SN, et al. Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. J Natl Cancer Inst 2007; 99: 1232–9PubMedCrossRefGoogle Scholar
  100. 100.
    Choueiri TK, Schutz FA, Je Y, et al. Risk of arterial thromboembolic events with sunitinib and sorafenib: a systematic review and meta-analysis of clinical trials. J Clin Oncol 2010; 28: 2280–5PubMedCrossRefGoogle Scholar
  101. 101.
    Schmidinger M, Zielinski CC, Vogl UM, et al. Cardiac toxicity of sunitinib and sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol 2008; 26: 5204–12PubMedCrossRefGoogle Scholar
  102. 102.
    Sternberg CN, Szczylik C, Lee E, et al. A randomized, double-blind phase III study of pazopanib in treatment-naive and cytokine-pretreated patients with advanced renal cell carcinoma (RCC). J Clin Oncol (Meet Abstr) 2009; 27: 5021Google Scholar
  103. 103.
    Zangari M, Fink LM, Elice F, et al. Thrombotic events in patients with cancer receiving antiangiogenesis agents. J Clin Oncol 2009; 27: 4865–73PubMedCrossRefGoogle Scholar
  104. 104.
    Baldo P, Cecco S, Giacomin E, et al. mTOR pathway and mTOR inhibitors as agents for cancer therapy. Curr Cancer Drug Targets 2008; 8: 647–65PubMedCrossRefGoogle Scholar
  105. 105.
    Osanto S, Hutson TE, Calvo E, et al. Efficacy and safety of everolimus in elderly patients (pts) with metastatic renal cell carcinoma (mRCC). J Clin Oncol (Meet Abstr) 2010; 28: 4608Google Scholar
  106. 106.
    Escudier B, Eisen T, Stadler WM, et al. Sorafenib for treatment of renal cell carcinoma: final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial. J Clin Oncol 2009; 27: 3312–8PubMedCrossRefGoogle Scholar
  107. 107.
    Halabi S, Rini BI, Stadler WM, et al. Use of progressionfree survival (PFS) to predict overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC). J Clin Oncol (Meet Abstr) 2010; 28: 4525Google Scholar
  108. 108.
    Motzer RJ, Escudier B, Oudard S, et al. Phase 3 trial of everolimus for metastatic renal cell carcinoma: final results and analysis of prognostic factors. Cancer 2010; 116: 4256–65PubMedCrossRefGoogle Scholar
  109. 109.
    Pal SK, Reckamp KL. Targeted pathways in NSCLC and SCLC. In: Kernstine K, editor. A multidisciplinary approach to lung cancer. New York (NY): Demos Medical Publishers, 2010Google Scholar

Copyright information

© Adis Data Information BV 2011

Authors and Affiliations

  • Sumanta K. Pal
    • 1
  • Ari Vanderwalde
    • 2
  • Arti Hurria
    • 3
  • Robert A. Figlin
    • 4
  1. 1.Division of Genitourinary Malignancies, Department of Medical Oncology & Experimental TherapeuticsCity of Hope Comprehensive Cancer CenterDuarteUSA
  2. 2.Department of Medical Oncology & Experimental TherapeuticsCity of Hope Comprehensive Cancer CenterDuarteUSA
  3. 3.Department of Medical Oncology & Experimental Therapeutics, Cancer Control and Population Sciences Program, and Cancer and Aging Research ProgramCity of Hope Comprehensive Cancer CenterDuarteUSA
  4. 4.Hematology-Oncology, Department of Medicine, Cedars-Sinai Medical CenterSamuel Oschin Comprehensive Cancer InstituteLos AngelesUSA

Personalised recommendations