Skip to main content
SpringerLink
Log in

Renal toxicity of targeted therapies

  • Review
  • Published:
Targeted Oncology Aims and scope Submit manuscript

Abstract

The use of molecular targeted therapies for the treatment of cancer has increased over the last decade. The benefits of these compounds in terms of efficacy are often relatively modest and counter balanced by the occurrence of significant toxicities. Many of these newer agents used in clinical practice lack specificity and selectivity and have a propensity to inhibit multiple targets. The biological consequences of multi-kinase activity are poorly defined and numerous class-specific toxicities have been described. The kidney is an organ where most of these targeted pathways are expressed. Preclinical data and human renal biopsies have generated an understanding of the mechanisms involved in how targeted agents can cause renal toxicity. This review article discusses the observed nephrotoxicity with this burgeoning class of therapeutics and reviews both the biological reasons for its occurrence and possible ways to prevent significant renal damage.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Dvorak HF (2002) Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. Clin Oncol 20(21):4368–4380

    Article  CAS  Google Scholar 

  2. Ellis LM, Hicklin DJ (2008) Pathways mediating resistance to vascular endothelial growth factor-targeted therapy. Clin Cancer Res 14(20):6371–6375

    Article  CAS  PubMed  Google Scholar 

  3. Lorusso PM, Eder JP (2008) Therapeutic potential of novel selective-spectrum kinase inhibitors in oncology. Expert Opin Investig Drugs 17(7):1013–1028

    Article  CAS  PubMed  Google Scholar 

  4. Raymond E, Faivre S, Armand JP (2000) Epidermal growth factor receptor tyrosine kinase as a target for anticancer therapy. Drugs 60(Suppl 1):15–23

    Article  CAS  PubMed  Google Scholar 

  5. Li J, Hampton T, Morgan JP, Simons M (1997) Stretch-induced VEGF expression in the heart. J Clin Invest 100(1):18–24

    Article  CAS  PubMed  Google Scholar 

  6. Maharaj AS, Saint-Geniez M, Maldonado AE, D’Amore PA (2006) Vascular endothelial growth factor localization in the adult. Am J Pathol 168(2):639–648

    Article  CAS  PubMed  Google Scholar 

  7. Maharaj AS, D’Amore PA (2007) Roles for VEGF in the adult. Microvasc Res 74(2–3):100–113

    Article  CAS  PubMed  Google Scholar 

  8. Couffinhal T, Kearney M, Witzenbichler B, Chen D, Murohara T, Losordo DW, Symes J, Isner JM (1997) Vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) in normal and atherosclerotic human arteries. Am J Pathol 150(5):1673–1685

    CAS  PubMed  Google Scholar 

  9. Stalmans I, Ng YS, Rohan R, Fruttiger M, Bouché A, Yuce A, Fujisawa H, Hermans B, Shani M, Jansen S, Hicklin D, Anderson DJ, Gardiner T, Hammes HP, Moons L, Dewerchin M, Collen D, Carmeliet P, D’Amore PA (2002) Arteriolar and venular patterning in retinas of mice selectively expressing VEGF isoforms. J Clin Invest 109(3):327–336

    CAS  PubMed  Google Scholar 

  10. Monacci WT, Merrill MJ, Oldfield EH (1993) Expression of vascular permeability factor/vascular endothelial growth factor in normal rat tissues. Am J Physiol 264(4 Pt 1):C995–C1002

    CAS  PubMed  Google Scholar 

  11. Kilic U, Kilic E, Järve A, Guo Z, Spudich A, Bieber K, Barzena U, Bassetti CL, Marti HH, Hermann DM (2006) Human vascular endothelial growth factor protects axotomized retinal ganglion cells in vivo by activating ERK-1/2 and Akt pathways. J Neurosci 26(48):12439–12446

    Article  CAS  PubMed  Google Scholar 

  12. Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF (1983) Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science. 219(4587):983–985

    Article  CAS  PubMed  Google Scholar 

  13. Krämer I, Lipp HP (2007) Bevacizumab, a humanized anti-angiogenic monoclonal antibody for the treatment of colorectal cancer. J Clin Pharm Ther 32(1):1–14

    Article  PubMed  Google Scholar 

  14. Presta LG, Chen H, O’Connor SJ, Chisholm V, Meng YG, Krummen L, Winkler M, Ferrara N (1997) Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res 57(20):4593–4599

    CAS  PubMed  Google Scholar 

  15. Tassev DV, Cheung NK (2009) Monoclonal antibody therapies for solid tumors. Expert Opin Biol Ther 9(3):341–353

    Article  CAS  PubMed  Google Scholar 

  16. Ferrara N, Hillan KJ, Gerber HP, Novotny W (2004) Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov 3(5):391–400

    Article  CAS  PubMed  Google Scholar 

  17. Dvorak HF (2002) Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J Clin Oncol 20(21):4368–4380

    Article  CAS  PubMed  Google Scholar 

  18. Gordon MS, Margolin K, Talpaz M, Sledge GW Jr, Holmgren E, Benjamin R, Stalter S, Shak S, Adelman D (2001) Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer. J Clin Oncol 19(3):843–850

    CAS  PubMed  Google Scholar 

  19. Frangié C, Lefaucheur C, Medioni J, Jacquot C, Hill GS, Nochy D (2007) Renal thrombotic microangiopathy caused by anti-VEGF-antibody treatment for metastatic renal-cell carcinoma. Lancet Oncol 8(2):177–178

    Article  PubMed  Google Scholar 

  20. Roncone D, Satoskar A, Nadasdy T, Monk JP, Rovin BH (2007) Proteinuria in a patient receiving anti-VEGF therapy for metastatic renal cell carcinoma. Nat Clin Pract Nephrol 3(5):287–293

    Article  PubMed  Google Scholar 

  21. Zhu X, Wu S, Dahut WL, Parikh CR (2007) Risks of proteinuria and hypertension with bevacizumab, an antibody against vascular endothelial growth factor: systematic review and meta-analysis. Am J Kidney Dis 49(2):186–193

    Article  CAS  PubMed  Google Scholar 

  22. Eremina V, Baelde HJ, Quaggin SE (2007) Role of the VEGF—a signaling pathway in the glomerulus: evidence for crosstalk between components of the glomerular filtration barrier. Nephron Physiol 106(2):32–37

    Article  Google Scholar 

  23. Eremina V, Jefferson JA, Kowalewska J, Hochster H, Haas M, Weisstuch J, Richardson C, Kopp JB, Kabir MG, Backx PH, Gerber HP, Ferrara N, Barisoni L, Alpers CE, Quaggin SE (2008) VEGF inhibition and renal thrombotic microangiopathy. N Engl J Med 358(11):1129–1136

    Article  CAS  PubMed  Google Scholar 

  24. Levine RJ, Lam C, Qian C, Yu KF, Maynard SE, Sachs BP, Sibai BM, Epstein FH, Romero R, Thadhani R, Karumanchi SA (2006) CPEP study group. Soluble endoglin and other circulating antiangiogenic factors in preeclampsia. N Engl J Med 355(10):992–1005

    Article  CAS  PubMed  Google Scholar 

  25. George BA, Zhou XJ, Toto R (2007) Nephrotic syndrome after bevacizumab: case report and literature review. Am J Kidney Dis 49(2):e23–e29

    Article  PubMed  Google Scholar 

  26. Hoenig MR, Bianchi C, Rosenzweig A, Sellke FW (2008) The cardiac microvasculature in hypertension, cardiac hypertrophy and diastolic heart failure. Curr Vasc Pharmacol 6(4):292–300

    Article  CAS  PubMed  Google Scholar 

  27. Izzedine H, Billemont B, Thibault F, Rixe O (2007) New challenges in kidney cancer therapy: sunitinib. Ann Oncol 18(Suppl 9):ix83–ix86

    Article  PubMed  Google Scholar 

  28. Faivre S, Delbaldo C, Vera K, Robert C, Lozahic S, Lassau N, Bello C, Deprimo S, Brega N, Massimini G, Armand JP, Scigalla P, Raymond E (2006) Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer. J Clin Oncol 24(1):25–35

    Article  CAS  PubMed  Google Scholar 

  29. 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

    Article  CAS  PubMed  Google Scholar 

  30. Bollée G, Patey N, Cazajous G, Robert C, Goujon JM, Fakhouri F, Bruneval P, Noël LH, Knebelmann B (2009) Thrombotic microangiopathy secondary to VEGF pathway inhibition by sunitinib. Nephrol Dial Transplant 24(2):682–685

    Article  PubMed  Google Scholar 

  31. Abou-Alfa GK, Schwartz L, Ricci S, Amadori D, Santoro A, Figer A, De Greve J, Douillard JY, Lathia C, Schwartz B, Taylor I, Moscovici M, Saltz LB (2006) Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol 24(26):4293–4300

    Article  CAS  PubMed  Google Scholar 

  32. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Häussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J, SHARP Investigators Study Group (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359(4):378–390

    Article  CAS  PubMed  Google Scholar 

  33. Chi KN, Ellard SL, Hotte SJ, Czaykowski P, Moore M, Ruether JD, Schell AJ, Taylor S, Hansen C, Gauthier I, Walsh W, Seymour L (2008) A phase II study of sorafenib in patients with chemo-naive castration-resistant prostate cancer. Ann Oncol 19(4):746–751

    Article  CAS  PubMed  Google Scholar 

  34. Dahut WL, Scripture C, Posadas E, Jain L, Gulley JL, Arlen PM, Wright JJ, Yu Y, Cao L, Steinberg SM, Aragon-Ching JB, Venitz J, Jones E, Chen CC, Figg WD (2008) A phase II clinical trial of sorafenib in androgen-independent prostate cancer. Clin Cancer Res 14(1):209–214

    Article  CAS  PubMed  Google Scholar 

  35. 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

    Article  CAS  PubMed  Google Scholar 

  36. Izzedine H, Brocheriou I, Rixe O, Deray G (2007) Interstitial nephritis in a patient taking sorafenib. Nephrol Dial Transplant 22(8):2411

    Article  PubMed  Google Scholar 

  37. Azad NS, Posadas EM, Kwitkowski VE, Steinberg SM, Jain L, Annunziata CM, Minasian L, Sarosy G, Kotz HL, Premkumar A, Cao L, McNally D, Chow C, Chen HX, Wright JJ, Figg WD, Kohn EC (2008) Combination targeted therapy with sorafenib and bevacizumab results in enhanced toxicity and antitumor activity. J Clin Oncol 26(22):3709–3714

    Article  CAS  PubMed  Google Scholar 

  38. Haase VH (2006) Hypoxia-inducible factors in the kidney. Am J Physiol Renal Physiol 291(2):F271–F281

    Article  CAS  PubMed  Google Scholar 

  39. Schofield CJ, Ratcliffe PJ (2004) Oxygen sensing by HIF hydroxylases. Nat Rev Mol Cell Biol 5(5):343–354

    Article  CAS  PubMed  Google Scholar 

  40. Bernhardt WM, Schmitt R, Rosenberger C, Münchenhagen PM, Gröne HJ, Frei U, Warnecke C, Bachmann S, Wiesener MS, Willam C, Eckardt KU (2006) Expression of hypoxia-inducible transcription factors in developing human and rat kidneys. Kidney Int 69(1):114–122

    Article  CAS  PubMed  Google Scholar 

  41. Greenberger LM, Horak ID, Filpula D, Sapra P, Westergaard M, Frydenlund HF, Albaek C, Schroder H, Orum H (2008) A RNA antagonist of hypoxia-inducible factor-1alpha, EZN-2968, inhibits tumor cell growth. Mol Cancer Ther 7(11):3598–3608

    Article  CAS  PubMed  Google Scholar 

  42. Lewis N, Cohen RB, Nishida Y et al (2008) Phase I, pharmacokinetic (PK), dose-escalation study of EZN 2968, a novel hypoxia-inducible factor-1alpha RNA antagonist, administered weekly in patients with solid tumors. 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, Geneva: abstract #398

  43. Bray SJ (2006) Notch signalling: a simple pathway becomes complex. Nat Rev Mol Cell Biol 7(9):678–689

    Article  CAS  PubMed  Google Scholar 

  44. Sainson RC, Harris AL (2008) Regulation of angiogenesis by homotypic and heterotypic notch signalling in endothelial cells and pericytes: from basic research to potential therapies. Angiogenesis 11(1):41–51

    Article  CAS  PubMed  Google Scholar 

  45. Noguera-Troise I, Daly C, Papadopoulos NJ, Coetzee S, Boland P, Gale NW, Lin HC, Yancopoulos GD, Thurston G (2006) Blockade of Dll4 inhibits tumour growth by promoting non-productive angiogenesis. Nature 444(7122):1032–1037

    Article  CAS  PubMed  Google Scholar 

  46. Pollak MR (2008) Focal segmental glomerulosclerosis: recent advances. Curr Opin Nephrol Hypertens 17(2):138–142

    Article  PubMed  Google Scholar 

  47. Cheng HT, Kim M, Valerius MT, Surendran K, Schuster-Gossler K, Gossler A, McMahon AP, Kopan R (2007) Notch2, but not Notch1, is required for proximal fate acquisition in the mammalian nephron. Development 134(4):801–811

    Article  CAS  PubMed  Google Scholar 

  48. Niranjan T, Bielesz B, Gruenwald A, Ponda MP, Kopp JB, Thomas DB, Susztak K (2008) The Notch pathway in podocytes plays a role in the development of glomerular disease. Nat Med 14(3):290–298

    Article  CAS  PubMed  Google Scholar 

  49. Kretzler M, Allred L (2008) Notch inhibition reverses kidney failure. Nat Med 14(3):246–247

    Article  CAS  PubMed  Google Scholar 

  50. Schechter AL, Hung MC, Vaidyanathan L, Weinberg RA, Yang-Feng TL, Francke U, Ullrich A, Coussens L (1985) The neu gene: an erbB-homologous gene distinct from and unlinked to the gene encoding the EGF receptor. Science 229(4717):976–978

    Article  CAS  PubMed  Google Scholar 

  51. Burgess AW (2008) EGFR family: structure physiology signaling and therapeutic targets. Growth Factors 26(5):263–274

    Article  CAS  PubMed  Google Scholar 

  52. Perez EA, Baweja M (2008) HER2-positive breast cancer: current treatment strategies. Cancer Invest 26(6):545–552

    Article  PubMed  Google Scholar 

  53. Arany I, Megyesi JK, Kaneto H, Tanaka S, Safirstein RL (2004) Activation of ERK or inhibition of JNK ameliorates H(2)O(2) cytotoxicity in mouse renal proximal tubule cells. Kidney Int 4:1231–1239

    Article  Google Scholar 

  54. Arany I, Megyesi JK, Reusch JE, Safirstein RL (2005) CREB mediates ERK-induced survival of mouse renal tubular cells after oxidant stress. Kidney Int 68(4):1573–1582

    Article  PubMed  Google Scholar 

  55. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabárbara P, Seymour L, National Cancer Institute of Canada Clinical Trials Group (2005) Erlotinib in previously treated non-small cell lung cancer. N Engl J Med 353(2):123–132

    Article  CAS  PubMed  Google Scholar 

  56. Miller AA, Murry DJ, Owzar K, Hollis DR, Lewis LD, Kindler HL, Marshall JL, Villalona-Calero MA, Edelman MJ, Hohl RJ, Lichtman SM, Ratain MJ (2007) Phase I and pharmacokinetic study of erlotinib for solid tumors in patients with hepatic or renal dysfunction: CALGB 60101. J Clin Oncol 25(21):3055–3060

    Article  CAS  PubMed  Google Scholar 

  57. Masutani K, Fujisaki K, Maeda H, Toyonaga J, Inoshima I, Takayama K, Katafuchi R, Hirakata H, Tsuruya K, Iida M (2008) Tubulointerstitial nephritis and IgA nephropathy in a patient with advanced lung cancer treated with long-term gefitinib. Clin Exp Nephrol 12(5):398–402

    Article  CAS  PubMed  Google Scholar 

  58. Kumasaka R, Nakamura N, Shirato K, Osawa H, Takanashi S, Hasegawa Y, Yamabe H, Nakamura M, Tamura M, Okumura K (2004) Side effects of therapy: case 1. Nephrotic syndrome associated with gefitinib therapy. J Clin Oncol 22(12):2504–2505

    Article  PubMed  Google Scholar 

  59. Lautrette A, Li S, Alili R, Sunnarborg SW, Burtin M, Lee DC, Friedlander G, Terzi F (2005) Angiotensin II and EGF receptor cross-talk in chronic kidney diseases: a new therapeutic approach. Nat Med 11(8):867–874

    Article  CAS  PubMed  Google Scholar 

  60. Patel DK (2008) Clinical use of anti-epidermal growth factor receptor monoclonal antibodies in metastatic colorectal cancer. Pharmacotherapy 28(11 Pt 2):31S–41S

    Article  CAS  PubMed  Google Scholar 

  61. Giro C, Berger B, Bölke E, Ciernik IF, Duprez F, Locati L, Maillard S, Ozsahin M, Pfeffer R, Robertson AG, Langendijk JA, Budach W (2009) High rate of severe radiation dermatitis during radiation therapy with concurrent cetuximab in head and neck cancer: results of a survey in EORTC institutes. Radiother Oncol 90(2):166–171

    Article  CAS  PubMed  Google Scholar 

  62. Nielsen DL, Andersson M, Kamby C (2009) HER2-targeted therapy in breast cancer. Monoclonal antibodies and tyrosine kinase inhibitors. Cancer Treat Rev 35(2):121–136

    Article  CAS  PubMed  Google Scholar 

  63. Nakanishi K, Sweeney W Jr, Avner ED (2001) Segment-specific c-ErbB2 expression in human autosomal recessive polycystic kidney disease. J Am Soc Nephrol 12(2):379–384

    CAS  PubMed  Google Scholar 

  64. Mir O, Berveiller P, Ropert S, Goffinet F, Pons G, Treluyer JM, Goldwasser F (2008) Emerging therapeutic options for breast cancer chemotherapy during pregnancy. Ann Oncol 19(4):607–613

    Article  CAS  PubMed  Google Scholar 

  65. Medina PJ, Goodin S (2008) Lapatinib: a dual inhibitor of human epidermal growth factor receptor tyrosine kinases. Clin Ther 30(8):1426–1447

    Article  CAS  PubMed  Google Scholar 

  66. Cassier PA, Dufresne A, Arifi S, El Sayadi H, Labidi I, Ray-Coquard I, Tabone S, Méeus P, Ranchère D, Sunyach MP, Decouvelaere AV, Alberti L, Blay JY (2008) Imatinib mesilate for the treatment of gastrointestinal stromal tumour. Expert Opin Pharmacother 9(7):1211–1222

    Article  CAS  PubMed  Google Scholar 

  67. Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM, Lydon NB, Kantarjian H, Capdeville R, Ohno-Jones S, Sawyers CL (2001) Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 344(14):1031–1037

    Article  CAS  PubMed  Google Scholar 

  68. Chevallier P, Hunault-Berger M, Larosa F, Dauriac C, Garand R, Harousseau JL (2008) A phase II trial of high-dose imatinib mesylate for relapsed or refractory c-kit positive and Bcr-Abl negative acute myeloid leukaemia: The AFR-15 trial. Leuk Res . doi:10.1016/j.leukres.2008.09.030

    Google Scholar 

  69. François H, Coppo P, Hayman JP, Fouqueray B, Mougenot B, Ronco P (2008) Partial fanconi syndrome induced by imatinib therapy: a novel cause of urinary phosphate loss. Am J Kidney Dis 51(2):298–301

    Article  PubMed  Google Scholar 

  70. Pou M, Saval N, Vera M, Saurina A, Solé M, Cervantes F, Botey A (2003) Acute renal failure secondary to imatinib mesylate treatment in chronic myeloid leukemia. Leuk Lymphoma 44(7):1239–1241

    Article  CAS  PubMed  Google Scholar 

  71. Foringer JR, Verani RR, Tjia VM, Finkel KW, Samuels JA, Guntupalli JS (2005) Acute renal failure secondary to imatinib mesylate treatment in prostate cancer. Ann Pharmacother 39(12):2136–2138

    Article  PubMed  Google Scholar 

  72. Deininger MW (2008) Nilotinib. Clin Cancer Res 14(13):4027–4031

    Article  CAS  PubMed  Google Scholar 

  73. Cortes J, Kim DW, Raffoux E, Martinelli G, Ritchie E, Roy L, Coutre S, Corm S, Hamerschlak N, Tang JL, Hochhaus A, Khoury HJ, Brümmendorf TH, Michallet M, Rege-Cambrin G, Gambacorti-Passerini C, Radich JP, Ernst T, Zhu C, Van Tornout JM, Talpaz M (2008) Efficacy and safety of dasatinib in imatinib-resistant or -intolerant patients with chronic myeloid leukemia in blast phase. Leukemia 22(12):2176–2183

    Article  CAS  PubMed  Google Scholar 

  74. Comoglio PM, Giordano S, Trusolino L (2008) Drug development of MET inhibitors: targeting oncogene addiction and expedience. Nat Rev Drug Discov 7(6):504–516

    Article  CAS  PubMed  Google Scholar 

  75. Liu Y, Yang J (2006) Hepatocyte growth factor: new arsenal in the fights against renal fibrosis? Kidney Int 70(2):238–240

    Article  CAS  PubMed  Google Scholar 

  76. Srinivasan R, Choueiri TK, Vaishampayan U, Rosenberg JE, Stein MN, Logan T, Bukowski RM, Mueller T, Keer HN, Linehan WM (2008) A phase II study of the dual MET/VEGFR2 inhibitor XL880 in patients (pts) with papillary renal carcinoma (PRC). J Clin Oncol 26(May 20 suppl):5103 abstract

    Google Scholar 

  77. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 130(6):461–470

    CAS  PubMed  Google Scholar 

  78. Launay-Vacher V, Oudard S, Janus N, Gligorov J, Pourrat X, Rixe O, Morere JF, Beuzeboc P, Deray G (2007) Renal insufficiency and cancer medications (IRMA) study group. Prevalence of renal insufficiency in cancer patients and implications for anticancer drug management: the renal insufficiency and anticancer medications (IRMA) study. Cancer 110(6):1376–1384

    Article  CAS  PubMed  Google Scholar 

  79. Kintzel PE (2001) Anticancer drug-induced kidney disorders. Drug Saf 24(1):19–38

    Article  CAS  PubMed  Google Scholar 

  80. Karaman MW, Herrgard S, Treiber DK, Gallant P, Atteridge CE, Campbell BT, Chan KW, Ciceri P, Davis MI, Edeen PT, Faraoni R, Floyd M, Hunt JP, Lockhart DJ, Milanov ZV, Morrison MJ, Pallares G, Patel HK, Pritchard S, Wodicka LM, Zarrinkar PP (2008) A quantitative analysis of kinase inhibitor selectivity. Nat Biotechnol 26(1):127–132

    Article  CAS  PubMed  Google Scholar 

  81. Izzedine H, Brocheriou I, Deray G, Rixe O (2007) Thrombotic microangiopathy and anti-VEGF agents. Nephrol Dial Transplant 22(5):1481–1482

    Article  PubMed  Google Scholar 

  82. Scartozzi M, Galizia E, Chiorrini S, Giampieri R, Berardi R, Ierantoni C, Cascinu S (2009) Arterial hypertension correlates with clinical outcome in colorectal cancer patients treated with first-line bevacizumab. Ann Oncol 20(2):227–230

    Article  CAS  PubMed  Google Scholar 

  83. Rixe O, Billemont B, Izzedine H (2007) Hypertension as a predictive factor of Sunitinib activity. Ann Oncol 18(6):1117

    Article  CAS  PubMed  Google Scholar 

  84. Rini BI, Schiller JH, Fruehauf JP, Cohen EE, Tarazi JC, Rosbrook B, Ricart AD, Olszanski AJ, Kim S, Spano J (2008) Association of diastolic blood pressure (dBP) ≥90 mmHg with overall survival (OS) in patients treated with axitinib (AG- 013736). J Clin Oncol 26(May 20 suppl):3543 abstract

    Google Scholar 

  85. Miller KD, Chap LI, Holmes FA, Cobleigh MA, Marcom PK, Fehrenbacher L, Dickler M, Overmoyer BA, Reimann JD, Sing AP, Langmuir V, Rugo HS (2005) Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol 23(4):792–799

    Article  CAS  PubMed  Google Scholar 

  86. Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, Shenkier T, Cella D, Davidson NE (2007) Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 357(26):2666–2676

    Article  CAS  PubMed  Google Scholar 

  87. Dickler MN, Rugo HS, Eberle CA, Brogi E, Caravelli JF, Panageas KS, Boyd J, Yeh B, Lake DE, Dang CT, Gilewski TA, Bromberg JF, Seidman AD, D’Andrea GM, Moasser MM, Melisko M, Park JW, Dancey J, Norton L, Hudis CA (2008) A phase II trial of erlotinib in combination with bevacizumab in patients with metastatic breast cancer. Clin Cancer Res 14(23):7878–7883

    Article  CAS  PubMed  Google Scholar 

  88. Dellapasqua S, Bertolini F, Bagnardi V, Campagnoli E, Scarano E, Torrisi R, Shaked Y, Mancuso P, Goldhirsch A, Rocca A, Pietri E, Colleoni M (2008) Metronomic cyclophosphamide and capecitabine combined with bevacizumab in advanced breast cancer. J Clin Oncol 26(30):4899–4905

    Article  CAS  PubMed  Google Scholar 

  89. Yang JC, Haworth L, Sherry RM, Hwu P, Schwartzentruber DJ, Topalian SL, Steinberg SM, Chen HX, Rosenberg SA (2003) A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 349(5):427–434

    Article  CAS  PubMed  Google Scholar 

  90. Escudier B, Pluzanska A, Koralewski P, Ravaud A, Bracarda S, Szczylik C, Chevreau C, Filipek M, Melichar B, Bajetta E, Gorbunova V, Bay JO, Bodrogi I, Jagiello-Gruszfeld A, Moore N, AVOREN Trial investigators (2007) Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: A randomised, double-blind phase III trial. Lancet 370(9605):2103–2111

    Article  PubMed  Google Scholar 

  91. Rini BI, Halabi S, Rosenberg JE, Stadler WM, Vaena DA, Ou SS, Archer L, Atkins JN, Picus J, Czaykowski P, Dutcher J, Small EJ (2008) Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol 26(33):5422–5428

    Article  CAS  PubMed  Google Scholar 

  92. Bukowski RM (2008) Randomized trial of bevacizumab in advanced renal cell carcinoma. Curr Oncol Rep 10(2):99–100

    Article  PubMed  Google Scholar 

  93. Johnson DH, Fehrenbacher L, Novotny WF, Herbst RS, Nemunaitis JJ, Jablons DM, Langer CJ, DeVore RF 3rd, Gaudreault J, Damico LA, Holmgren E, Kabbinavar F (2004) Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol 22(11):2184–2191

    Article  CAS  PubMed  Google Scholar 

  94. Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355(24):2542–2550

    Article  CAS  PubMed  Google Scholar 

  95. Herbst RS, Johnson DH, Mininberg E, Carbone DP, Henderson T, Kim ES, Blumenschein G Jr, Lee JJ, Liu DD, Truong MT, Hong WK, Tran H, Tsao A, Xie D, Ramies DA, Mass R, Seshagiri S, Eberhard DA, Kelley SK, Sandler A (2005) Phase I/II trial evaluating the anti-vascular endothelial growth factor monoclonal antibody bevacizumab in combination with the HER-1/epidermal growth factor receptor tyrosine kinase inhibitor erlotinib for patients with recurrent non-small-cell lung cancer. J Clin Oncol 23(11):2544–2555

    Article  CAS  PubMed  Google Scholar 

  96. Herbst RS, O’Neill VJ, Fehrenbacher L, Belani CP, Bonomi PD, Hart L, Melnyk O, Ramies D, Lin M, Sandler A (2007) Phase II study of efficacy and safety of bevacizumab in combination with chemotherapy or erlotinib compared with chemotherapy alone for treatment of recurrent or refractory non small-cell lung cancer. J Clin Oncol 25(30):4743–4750

    Article  CAS  PubMed  Google Scholar 

  97. Hochster HS, Hart LL, Ramanathan RK, Childs BH, Hainsworth JD, Cohn AL, Wong L, Fehrenbacher L, Abubakr Y, Saif MW, Schwartzberg L, Hedrick E (2008) Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: results of the TREE study. J Clin Oncol 26(21):3523–3529

    Article  CAS  PubMed  Google Scholar 

  98. Saltz LB, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzen F, Cassidy J (2008) Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 26(12):2013–2019

    Article  CAS  PubMed  Google Scholar 

  99. Tol J, Koopman M, Rodenburg CJ, Cats A, Creemers GJ, Schrama JG, Erdkamp FL, Vos AH, Mol L, Antonini NF, Punt CJ (2008) A randomised phase III study on capecitabine, oxaliplatin and bevacizumab with or without cetuximab in first-line advanced colorectal cancer, the CAIRO2 study of the dutch colorectal cancer group (DCCG). an interim analysis of toxicity. Ann Oncol 19(4):734–738

    Article  CAS  PubMed  Google Scholar 

  100. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350(23):2335–2342

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank the Fondation Martine Midy, Paris, France for technical assistance in preparation of this manuscript.

Conflict of interest statement

No funds were received in support of this study, nor were any benefits received from a commercial party related directly or indirectly to the subject of this manuscript, except those directed solely to a research fund, foundation, educational institution or other non-profit organization with which one or more of the author(s) is/are associated.

Author information

Authors and Affiliations

  1. National Cancer Institute, Medical Oncology Branch, Center for Cancer Research, Bethesda, MD, 20892, USA

    Ronan J. Kelly & Olivier Rixe

  2. CERIA (Centre d’Etudes et de Recours sur les Inhibiteurs de l’Angiogenese), Cochin Hospital, Paris, France

    Bertrand Billemont

Authors
  1. Ronan J. Kelly
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bertrand Billemont
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Olivier Rixe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Olivier Rixe.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kelly, R.J., Billemont, B. & Rixe, O. Renal toxicity of targeted therapies. Targ Oncol 4, 121–133 (2009). https://doi.org/10.1007/s11523-009-0109-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11523-009-0109-x

Keywords

Search

Navigation