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ZD1839 (‘Iressa’)1,2 as an Anticancer Agent

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Abstract

ZD1839 (‘lressa’)1,2 is an orally active, selective epidermal growth factor receptor-tyrosine kinase inhibitor which blocks signal transduction pathways implicated in the proliferation and survival of cancer cells and other host-dependent processes promoting cancer growth. In preclinical studies, ZD1839 produced reversible growth inhibition and growth delay in a wide range of tumour cell lines and human tumour xenografts. Moreover, this activity was enhanced when ZD1839 was coadministered with cytotoxic agents. Preliminary results from phase I trials in patients with advanced disease and a wide variety of tumour types suggest that ZD1839 has an acceptable tolerability profile and promising clinical efficacy, particularly in non-small cell lung cancer (NSCLC). ZD1839 is currently in phase III clinical development for the treatment of advanced NSCLC. In addition, further trials are ongoing or planned in a number of other tumour types.

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Notes

  1. ‘Iressa’ is a trademark of the AstraZeneca group of companies.

  2. Use of a trade name is for product identification purposes only, and does not imply endorsement.

References

  1. Olayioye MA, Neve RM, Lane HA, et al. The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J 2000; 19: 3159–67

    Article  PubMed  CAS  Google Scholar 

  2. Lemmon MA, Schlessinger J. Regulation of signal transduction and signal diversity by receptor oligomerization. Trends Biochem Sci 1994; 19: 459–63

    Article  PubMed  CAS  Google Scholar 

  3. Favoni RE, de Cupis A. The role of polypeptide growth factors in human carcinomas; new targets for a novel pharmacological approach. Pharmacol Rev 2000; 52: 179–206

    PubMed  CAS  Google Scholar 

  4. Aaronson SA. Growth factors and cancer. Science 1991; 254: 1146–53

    Article  PubMed  CAS  Google Scholar 

  5. Wells A. EGF receptor. Int J Biochem Cell Biol 1999; 31: 637–43

    Article  PubMed  CAS  Google Scholar 

  6. Woodburn JR. The epidermal growth factor receptor and its inhibition in cancer therapy. Pharmacol Ther 1999; 82 (2–3): 241–50

    Article  Google Scholar 

  7. Salomon DS, Brandt R, Ciardiello F, et al. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol 1995; 19: 183–232

    Article  PubMed  CAS  Google Scholar 

  8. Voldborg BR, Damstrup L, Spang-Thomsen M, et al. Epidermal growth factor receptor (EGFR) and EGFR mutations, function and possible role in clinical trials. Ann Oncol 1997; 8: 1197–206

    Article  PubMed  CAS  Google Scholar 

  9. Batra SK, Castelino Prabhu S, Wikstrand CJ, et al. Epidermal growth factor ligand-independent, unregulated, cell-transforming potential of a naturally occurring human mutant EGFRvIII gene. Cell Growth Differ 1995; 6(10): 1251–9

    PubMed  CAS  Google Scholar 

  10. Chu CT, Everiss KD, Wikstrand CJ, et al. Receptor dimerization is not a factor in the signalling activity of a transforming variant epidermal growth factor receptor (EGFRvIII). Biochem J 1997; 324 (Pt 3): 855–61

    PubMed  CAS  Google Scholar 

  11. Pawson T. Tyrosine kinases and their interactions with signalling proteins. Curr Opin Genet Dev 1992; 2: 4–12

    Article  PubMed  CAS  Google Scholar 

  12. Woodburn J, Kendrew J, Fennell M, et al. ZD1839 (‘Iressa’) a selective epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI): inhibition of c-fos mRNA, an intermediate marker of EGFR activation, correlates with tumor growth inhibition [abstract no. 2552]. Presented at the American Association of Cancer Research: 2000 Apr 1–5; San Francisco, USA. Proc Amer Assoc Cancer Res 2000; 41

  13. Woodburn JR, Barker AJ, Wakeling AE, et al. 6-amino-4 (3-methyl-phenylamino)-quinazoline: an EGF receptor tyrosine kinase inhibitor with activity in a range of human tumour xenografts. Proc Am Assoc Cancer Res 1996; 36: 390–1

    Google Scholar 

  14. Budillon A, Di Gennaro E, Barbarino M, et al. ZD1839, an epidermal growth factor receptor tyrosine kinase inhibitor, upregulates p27KiP1 inducing G1 arrest and enhancing the antitumor effect of Interferon a [abstract no. 4910]. Presented at the American Association of Cancer Research: 2000 Apr 1–5; San Francisco, USA. Proc Amer Assoc Cancer Res 2000; 41

  15. Lane HA, Beuvink I, Motoyama AB, et al. ErbB2 potentiates breast tumor proliferation through modulation of p27Kip1-CdK2 complex formation: receptor overexpression does not determine growth dependency. Mol Cell Biol 2000: 20: 3210–23

    Article  PubMed  CAS  Google Scholar 

  16. Ciardiello F, Caputo R, Bianco R, et al. Antitumor effect and potentiation of cytotoxic drugs activity in human cancer cells by ZD-1839 (Iressa), an epidermal growth factor receptor-selective tyrosine kinase inhibitor. Clin Cancer Res 2000; 6: 2053–63

    PubMed  CAS  Google Scholar 

  17. Cullinane C, Kleinschmidt M, Webster LK. Antitumour activity of ZD1839 (‘Iressa’) in combination with cisplatin in NIH3T3 cells expressing human epidermal growth factor receptor [abstract no. 3073]. Presented at the American Association of Cancer Research: 2000 Apr 1–5; San Francisco, USA. Proc Amer Assoc Cancer Res 2000; 41

  18. Sirotnak FM, Zakowsky MF, Miller VA, et al. Potentiation of cytotoxic agents against human tumors in mice by ZD1839 (Iressa™), an inhibitor of EGFR tyrosine kinase, does not require high levels of expression of EGFR [abstractno. 3076]. Presented at the American Association of Cancer Research: 2000 Apr 1–5; San Francisco, USA. Proc Amer Assoc Cancer Res 2000; 41

  19. Chan KC, Knox F, Woodburn JR, et al. EGFR tyrosine kinase inhibition decreases epithelial proliferation in DCIS of the breast, whereas c-erbB2 blockade does not [abstract no. 3074]. Presented at the American Association of Cancer Research: 2000 Apr 1–5; San Francisco, USA. Proc Amer Assoc Cancer Res 2000; 41

  20. Kelly HC, Laight A, Morris CQ, et al. Phase I data of ZD 1839-an oral epidermal growth factor receptor tyrosine kinase inhibitor [abstract no 419]. Ann Oncol 1998; 2: 109

    Google Scholar 

  21. Kelly HC, Ferry D, Hammond L, et al. ZD1839 (‘Iressa’), an oral EGFR-TKI (epidermal growth factor tyrosine kinase inhibitor): pharmacokinetics in a Phase I study of patients with advanced cancer [abstract no. 3896]. Presented at the American Association of Cancer Research: 2000 Apr 1–5; San Francisco, USA. Proc Amer Assoc Cancer Res 2000; 41

  22. Goss G, Hirte H, Batist G, et al. NCIC CTG IND.122: a two-part Phase I pharmacokinetic (PK) and pharmacodynamic (PD) study of the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) ZD1839 [abstract no 880]. Proc Am Soc Clin Oncol 2000; 19: 225a

    Google Scholar 

  23. Baselga J, Herbst R, LoRusso P, et al. Continuous administration of ZD1839 (Iressa), a novel oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), in patients with five selected tumor types: evidence of activity and good tolerability [abstract no 686]. Proc Am Soc Clin Oncol 2000; 19: 177a

    Google Scholar 

  24. Nakagawa K, Yamamoto N, Kudoh S, et al. A Phase I intermittent dose-escalation trial of ZD1839 (Iressa) in Japanese patients with solid malignant tumours [abstract no 711]. Proc Am Soc Clin Oncol 2000; 19: 183a

    Google Scholar 

  25. Ferry D, Hammond L, Ranson M, et al. Intermittent oral ZD1839 (Iressa), a novel epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), shows evidence of good tolerability and activity: final results from a Phase I study [abstract no 5E]. Proc Am Soc Clin Oncol 2000; 19: 3a

    Google Scholar 

  26. Shepherd FA. Chemotherapy for non-small cell lung cancer: have we reached a new plateau? Semin Oncol 1999; 26 (1 Suppl. 4): 3–11

    PubMed  CAS  Google Scholar 

  27. Johnson DH. Evolution of cisplatin-based chemotherapy in non-small cell lung cancer: a historical perspective and the eastern cooperative oncology group experience. Chest 2000; 117 Suppl. 1: 133–7

    Article  Google Scholar 

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Authors and Affiliations

  1. Medical Oncology Service, Vall d’Hebron University Hospital, Barcelona, Spain

    José Baselga

  2. AstraZeneca Pharmaceuticals, Wilmington, Delaware, USA

    Steven D. Averbuch

Authors
  1. José Baselga
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  2. Steven D. Averbuch
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Baselga, J., Averbuch, S.D. ZD1839 (‘Iressa’)1,2 as an Anticancer Agent. Drugs 60 (Suppl 1), 33–40 (2000). https://doi.org/10.2165/00003495-200060001-00004

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