International Journal of Radiation Oncology * Biology * Physics
Volume 62, Issue 2 , Pages 309-317 , 1 June 2005

Expression of the epidermal growth factor receptor and Her-2 are predictors of favorable outcome and reduced complete response rates, respectively, in patients with muscle-invading bladder cancers treated by concurrent radiation and cisplatin-based chemotherapy: A report from the Radiation Therapy Oncology Group

  • Arnab Chakravarti, M.D.

      Affiliations

    • Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA
    • Corresponding Author InformationReprint requests to: Arnab Chakravarti, M.D., Massachusetts General Hospital, Department of Radiation Oncology, 100 Blossom Street, Founders House, Room 536, Boston, MA 02114. Tel: (617) 724-1175; Fax: (617) 726-2098
    • ,
  • Kathryn Winter, M.S.

      Affiliations

    • Department of Biostatistics, Radiation Therapy Oncology Group, LDS Hospital, Salt Lake City, UT
    • ,
  • Chin-Lee Wu, M.D., Ph.D.

      Affiliations

    • Department of Pathology, Massachusetts General Hospital, Boston, MA
    • ,
  • Donald Kaufman, M.D.

      Affiliations

    • Department of Medical Oncology, Massachusetts General Hospital, Boston, MA
    • ,
  • Elizabeth Hammond, M.D.

      Affiliations

    • Department of Pathology, LDS Hospital, Salt Lake City, UT
    • ,
  • Matthew Parliament, M.D.

      Affiliations

    • Department of Radiation Oncology, Cross Center Institute, Edmonton, Alberta, Canada
    • ,
  • William Tester, M.D.

      Affiliations

    • Department of Radiation Oncology, Albert Einstein Cancer Center, Philadelphia, PA
    • ,
  • Michael Hagan, M.D.

      Affiliations

    • Department of Radiation Oncology, Medical College of Virginia, Richmond, VA
    • ,
  • David Grignon, M.D.

      Affiliations

    • Department of Pathology, Harper Hospital, Detroit, MI
    • ,
  • Niall Heney, M.D.

      Affiliations

    • Department of Urology, Massachusetts General Hospital, Boston, MA
    • ,
  • Alan Pollack, M.D., Ph.D.

      Affiliations

    • Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA
    • ,
  • Howard Sandler, M.D.

      Affiliations

    • Department of Radiation Oncology, University of Michigan, Ann Arbor, MI
    • ,
  • William Shipley, M.D.

      Affiliations

    • Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA

Received 15 April 2004 ,Revised 13 September 2004 ,Accepted 16 September 2004.

References 

  1. Baselga J , Mendelsohn J . The epidermal growth factor receptor as a target for therapy in breast carcinoma . Breast Cancer Res Treat . 1994;29:127–138
  2. Baselga J . The EGFR as a target for anticancer therapy—focus on cetuximab . Eur J Cancer . 2001;37(Suppl. 4):S16–S22
  3. Bianco C , Bianco R , Tortora G . Antitumor activity of combined treatment of human cancer cells with ionizing radiation and anti-epidermal growth factor receptor monoclonal antibody C225 plus type I protein kinase A antisense oligonucleotide . Clin Cancer Res . 2000;6:4343–4350
  4. Ciardielllo F , Bianco R , Damiano V . Antitumor activity of sequential treatment with topotecan and anti-epidermal growth factor receptor monoclonal antibody C225 . Clin Cancer Res . 1999;5:909–916
  5. Abdul-Manan N , Aghazadeh B , Liu GA , et al.   Structure of Cdc42 in complex with the GTPase-binding domain of the Wiskott-Aldrich syndrome’ protein . Nature . 1999;399:379–383
  6. Grandis JR , Chakraborty A , Melhem MF , et al.   Inhibition of epidermal growth factor receptor gene expression and function decreases proliferation of head and neck squamous cell carcinoma but not normal mucosal epithelial cells . Oncogene . 1997;15:409–416
  7. Esteller M , Garcia-Foncillas J , Andion E , et al.   Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents . N Engl J Med . 2000;343:1350–1354
  8. Hidalgo A , Sanz-Rodriguez F , Rodriguez-Fernandez JL , et al.   Chemokine stromal cell-derived factor-1alpha modulates VLA-4 integrin-dependent adhesion to fibronectin and VCAM-1 on bone marrow hematopoietic progenitor cells . Exp Hematol . 2001;29:345–355
  9. Beenken SW , Sellers MT , Huang P , et al.   Transforming growth factor alpha (TGF-alpha) expression in dysplastic oral leukoplakia (Modulation by 13-cis retinoic acid) . Head Neck . 1999;21:566–573
  10. Endo S , Zeng Q , Burke NA , et al.   TGF-alpha antisense gene therapy inhibits head and neck squamous cell carcinoma growth in vivo . Gene Ther . 2000;7:1906–1914
  11. Milas L , Mason K , Hunter N . In vivo enhancement of tumor radioresponse by C225 antiepidermal growth factor receptor antibody . Clin Cancer Res . 2000;6:701–708
  12. Chakravarti A , Chakladar A , Delaney MA , et al.   The epidermal growth factor receptor pathway mediates resistance to sequential administration of radiation and chemotherapy in primary human glioblastoma cells in a ras-dependent manner . Cancer Res . 2002;62:4307–4315
  13. Chakravarti A , Loeffler JS , Dyson NJ . Insulin-like growth factor receptor I mediates resistance to anti-epidermal growth factor receptor therapy in primary human glioblastoma cells through continued activation of phosphoinositide 3-kinase signaling . Cancer Res . 2002;62:200–207
  14. O’Rourke D , Kao GD , Singh N , et al.   Conversion of a radio-resistant phenotype to a more sensitive one by disabling erbB receptor signaling in human cancer cells . Proc Natl Acad Sci USA . 1998;95:10842–10847
  15. Altiok S , Batt D , Altiok N , et al.   Heregulin induces phosphorylation of BRCA1 through phosphatidylinositol 3-Kinase/AKT in breast cancer cells . J Biol Chem . 1999;274:32274–32278
  16. Harari PM , Huang S-M . Combining EGFR inhibitors with radiation or chemotherapy (Will pre-clinical studies predict clinical results?) . Int J Radiat Oncol Biol Phys . 2004;58:976–983
  17. Hackel PO , Zwick E , Prenzel N , et al.   Epidermal growth factor receptors (Critical mediators of multiple receptor pathways) . Curr Opin Cell Biol . 1999;11:184–189
  18. Woodburn JR . The epidermal growth factor receptor and its inhibition in cancer therapy . Pharmacol Ther . 1999;82:241–250
  19. Davis ID , MacRae Dell K , Sweeney WE , et al.   Can progression of autosomal dominant or autosomal recessive polycystic kidney disease be prevented? . Semin Nephrol . 2001;21:430–440
  20. Haas-Kogan D , Shalev N , Wong M , et al.   Protein kinase B (PKB/Akt) activity is elevated in glioblastoma cells due to mutation of the tumor suppressor PTEN/MMAC . Curr Biol . 1998;8:1195–1198
  21. Levitzki A . Targeting signal transduction for disease therapy . Curr Opin Cell Biol . 1996;8:239–244
  22. Schenk PW , Snaar-Jagalska BE . Signal perception and transduction (The role of protein kinases) . Biochim Biophys Acta . 1999;1449:1–24
  23. Schlegel J , Piontek G , Budde B , et al.   The akt/protein kinase B-dependent anti-apoptotic pathway and the mitogen-activated protein kinase cascade are alternatively activated in human glioblastoma multiforme . Cancer Lett . 2000;158:103–108
  24. Salomon DS , Brandt R , Ciardielllo F , et al.   Epidermal growth factor-related peptides and their receptors in human malignancies . Crit Rev Oncol Haematol . 1995;19:183–232
  25. Nelson JM , Fry DW . Akt, MAPK (Erk 1,2) and p38 act in concert to promote apoptosis in response to ErbB receptor family inhibition . J Biol Chem . 2001;276:14842–14847
  26. Nunez G , del Peso L . Linking extracellular survival signals and the apoptotic machinery . Curr Opin Neurobiol . 1998;8:613–618
  27. Moscatello DK , Montgomery RB , Sundareshan P , et al.   Transformation and altered signal transduction by a naturally occurring mutant EGF receptor . Oncogene . 1996;13:85–96
  28. Hashimoto A , Kurosaki M , Gotoh N , et al.   Shc regulates epidermal growth factor-induced activation of the JNK signaling pathway . J Biol Chem . 1999;274:20139–20143
  29. Haas-Kogan DA , Dazin P , Hu L , et al.   p53-Independent apoptosis (A mechanism of radiation-induced cell death of glioblastoma cells) . Cancer J Sci Am . 1996;2:114
  30. Chaudhary LR , Hruska KA . The cell survival signal akt is differentially activated by PDGF-BB, EGF, and FGF-2 in osteoblastic cells . J Cellular Biochem . 2001;81:304–311
  31. Ahrendt SA , Halachmi S , Chow JT , et al.   Rapid p53 sequence analysis in primary lung cancer using an oligonucleotide probe array . Proc Natl Acad Sci U S A . 1999;96:7382–7387
  32. Chen J , Wu W , Tahir SK , et al.   Down-regulation of survivin by antisense oligonucleotides increases apoptosis, inhibits cytokinesis and anchorage-independent growth . Neoplasia . 2000;2:235–241
  33. Bowers G , Reardon DB , Hewitt T , et al.   The relative role of ErbB1-4 receptor tyrosine kinases in radiation signal transduction responses of human carcinoma cells . Oncogene . 2001;20:1388–1397
  34. Bonner JA , Raisch KP , Trummell HQ . Enhanced apoptosis with combination C225/radiation treatment serves as the impetus for clinical investigation in head and neck cancers . J Clin Oncol . 2000;18:47s–53s
  35. Balaban N , Moni J , Shannon M , et al.   The effect of ionizing radiation on signal transduction (Antibodies to EGF receptor sensitize A431 cells to radiation) . Biochim Biophys Acta . 1996;1314:147–156
  36. Dominguez-Escrig JL , Kelly JD , Neal DE , et al.   Evaluation of the therapeutic potential of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib in preclinical models of bladder cancer . Clin Cancer Res . 2004;10:4874–4884
  37. Nutt JE , Lazarowicz HP , Mellon JK , et al.   Gefitinib inhibits the growth response of bladder tumour cell lines to epidermal growth factor and induces TIMP2 . Br J Cancer . 2004;90:1679–1685
  38. Tester W , Caplan R , Heaney J , et al.   Neoadjuvant combined modality program with selective organ preservation for invasive bladder cancer (Results of Radiation Therapy Oncology Group phase II trial 8802) . J Clin Oncol . 1996;14:119–126
  39. Rozycka M , Lu YJ , Brown RA , et al.   cDNA cloning of a third human C2-domain-containing class II phosphoinositide 3-kinase, PI3K-C2gamma, and chromosomal assignment of this gene (PIK3C2G) to 12p12 . Genomics . 1998;54:569–574
  40. Kaufman DS , Winter KA , Shipley WU , et al.   The initial results in muscle-invading bladder cancer of RTOG 95–06 (Phase I/II trial of transurethral surgery plus radiation therapy with concurrent cisplatin and 5-fluorouracil followed by selective bladder preservation or cystectomy depending on the initial response) . Oncologist . 2000;5:471–476
  41. Hagan MP , Winter KA , Kaufman DS , et al.   Initial report of a phase I/II trial of bladder conservation employing TURB, accelerated radiation sensitized with cisplatin, followed by adjuvant MCV . Int J Radiat Oncol Biol Phys . 2003;57:665–672
  42. Chen J , Hanafusa T , Wang L-H . Ala-Gly mutation in the putative catalytic loop confers temperature sensitivity on Ros, insulin receptor, and insulin-like growth factor I receptor protein-tyrosine kinases . Proc Nat Acad Sci . 1994;91:321–325
  43. Grignon DJ , Caplan R , Sarkar FH , et al.   p53 status and prognosis of locally advanced prostatic adenocarcinoma (A study based on RTOG 8610) . J Natl Cancer Inst . 1997;89:158–165
  44. Sarkis AS , Dalbagni G , Cordon-Cardo C , et al.   Nuclear overexpression of p53 protein in transitional cell bladder carcinoma (A marker for disease progression) . J Natl Cancer Inst . 1993;85:53–59
  45. Kaplan EL , Meier P . Nonparametric estimation from incomplete observations . J Am Stat Assoc . 1958;53:457–481
  46. Mantel N . Evaluation of survival data and two new rank order statistics arising in its consideration . Cancer Chem Rep . 1966;5:163–170
  47. Gaynor JJ , Feuer EJ , Tan CC . On the use of cause-specific and conditional failure probabilities . J Am Stat Assoc . 1993;88:400–409
  48. Gray RJ . A class of K-sample tests for comparing the cumulative incidence of a competing risk . Ann Stat . 1988;16:1141–1154
  49. Seigne JD , Dayton SH , Zhang DS , et al.   The p53 tumor suppressor gene as a potential prognostic marker in invasive bladder cancer . J Urol . 1992;147:338A
  50. Lipponen P , Eskelinen M . Expression of epidermal growth factor receptor in bladder cancer as related to established prognostic factors, oncoprotein (c-erbB-2, p53) expression and long-term prognosis . Br J Cancer . 1994;69:1120–1125
  51. Mellon K , Wright C , Kelly P , et al.   Long-term outcome related to epidermal growth factor receptor status in bladder cancer . J Urol . 1995;153:919–925
  52. Amagase H , Tamura K , Hashimoto K , et al.   Response of A431 experimental human solid xenograft to mitomycin C in combination with human epidermal growth factor in mice . J Pharmacobiodyn . 1990;13:263–268
  53. Tokunaga H , Shariat S , Green AE , et al.   Correlation of immunohistochemical molecular staging of bladder biopsies and radical cystectomy specimens . Int J Radiat Oncol Biol Phys . 2001;51:16–22
  54. Schultz TK , Herr HW , Zhang ZF . Neoadjuvant chemotherapy for invasive bladder cancer (Prognostic factors for survival in patients treated with MVAC with 5 year follow-up) . J Clin Oncol . 1994;12:1394–1401
  55. Friedman HS , Petros WP , Friedman AH , et al.   Irinotecan therapy in adults with recurrent or progressive malignant glioma . J Clin Oncol . 1999;17:1516–1525
  56. Horwich A , Pendlebury S , Dearnaley DP . Organ preservation in bladder cancer . Eur J Cancer . 1995;31:208
  57. Ang K , Berkey B , Tu X , et al.   Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma . Cancer Res . 2002;62:7350–7356
  58. Chakravarti A , Loeffler JS , Dyson NJ . Insulin-like growth factor receptor I mediates resistance to anti-epidermal growth factor receptor therapy in primary human glioblastoma cells through the continued activation of phosphoinositide 3-kinase signaling . Cancer Res . 2002;62:200–207
  59. Elledge R , Green S , Ciocca D , et al.   Her-2 expression and response to tamoxifen in estrogen receptor-positive breast cancer (A Southwest Oncology Group Study) . Clin Cancer Res . 1998;4:7–12
  60. del Muro XG , Condom E , Vigues F , et al.   p53 and p21 expression levels predict organ preservation and survival in invasive bladder carcinoma treated with a combined modality approach . Cancer . 2004;100:1859–1867

 This study was supported by RTOG U10 CA21661, CCOP U10 CA37422, and Stat U10 CA32115 grants from the NCI. The contents of this manuscript are the sole responsibility of the authors and do not necessarily represent the official views of the NCI.

PII: S0360-3016(04)02676-8

doi: 10.1016/j.ijrobp.2004.09.047

International Journal of Radiation Oncology * Biology * Physics
Volume 62, Issue 2 , Pages 309-317 , 1 June 2005

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