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01.10.2002 | Adis New Drug Profile

Gefitinib

verfasst von: Christine R. Culy, Diana Faulds

Erschienen in: Drugs | Ausgabe 15/2002

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Abstract

▴ Gefitinib (ZD1839) is an orally active selective inhibitor of epidermal growth factor receptor tyrosine kinase, an enzyme that regulates intracellular signalling pathways implicated in the proliferation and survival of cancer cells.
▴ In human non-small cell lung cancer (NSCLC) cell lines and xenografts, gefitinib dose-dependently inhibited cellular proliferation and tumour growth, and potentiated the cytotoxic effects of chemotherapy and/or radiation.
▴ Gefitinib is orally bioavailable and is cleared via the cytochrome P450 3A4 pathway. In patients receiving gefitinib (50 to 700 mg/day) in phase I trials, steady-state plasma concentration was reached in 7 to 10 days.
▴ In patients with advanced NSCLC who had failed one or two prior chemotherapies, gefitinib 250 or 500mg once daily induced an objective response in ≈19% of patients in a double-blind trial (n = 210).
▴ In another double-blind trial including 216 patients with NSCLC who had failed two or more prior chemotherapies, gefitinib 250 or 500mg once daily induced an objective response in 11.8 and 8.8% of patients, respectively; ≈40% showed an improvement in disease-related symptoms.
▴ Gefitinib was generally well tolerated and the most common adverse events were mild skin rashes and diarrhoea.

Iressa™

Cersosimo RJ. Lung Cancer: a review. Am J Health-Syst Pharm 2002 Apr 1; 59: 611–42PubMed

World Health Organization. World Health Organization Mortality Database [online]. Available from URL: http://www-dep.iarc.fr/ [Accessed 2002 June 12].

National Cancer Institute. Non-small cell lung cancer: treatment [online]. Available from URL: http://www.cancer.gov [Accessed 2002 July 23].

Non-small Cell Lung Cancer Collaborative Group. Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials. BMJ 1995 Oct 7; 311(7010): 899–909CrossRef

Shepherd FA, Dancey J, Ramlau R, et al. Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol 2000 May; 18(10): 2095–103PubMed

Fossella FV, DeVore R, Kerr RN, et al. on behalf of the TAX 320 Non-Small Cell Lung Cancer Study Group. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. J Clin Oncol 2000 Jun; 18(12): 2354–62PubMed

Olayioye MA, Neve RM, Lane HA, et al. The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J 2000 Jul 3; 19(13): 3159–67PubMedCrossRef

Baselga J, Averbuch SD. ZD1839 (‘Iressa’) as an anticancer agent. Drugs 2000; 60 Suppl. 1: 33–40; discussion 41–2CrossRef

Salomon DS, Brandt R, Ciardiello F, et al. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol 1995 Jul; 19(3): 183–232PubMedCrossRef

10.

Wakeling AE, Barker AJ, Davies DH, et al. Specific inhibition of epidermal growth factor receptor tyrosine kinase by 4-an-ilinoquinazolines. Breast Cancer Res Treat 1996; 38(1): 67–73PubMedCrossRef

11.

Albanell J, Rojo F, Baselga J. Pharmacodynamic studies with the epidermal growth factor receptor tyrosine kinase inhibitor ZD1839. Semin Oncol 2001 Oct; 28 (5 Suppl. 16): 56–66PubMedCrossRef

12.

Arteaga CL, Johnson DH. Tyrosine kinase inhibitors-ZD1839 (Iressa). Curr Opin Oncol 2001 Nov; 13(6): 491–8PubMedCrossRef

13.

Barker AJ, Gibson KH, Grundy W, et al. Studies leading to the identification of ZD1839 (IRESSA™): an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor targeted to the treatment of cancer. Bioorg Med Chem Lett 2001 Jul 23; 11(14): 1911–4PubMedCrossRef

14.

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

15.

Woodburn JR, 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. 91st Annu Meet Am Assoc Cancer Res 2000 Mar; 41: 402 (abstract no. 2552)

16.

Albanell J, Codony-Servat J, Rojo F, et al. Activated extracellular signal-regulated kinases: association with epidermal growth factor receptor/transforming growth factor alpha expression in head and neck squamous carcinoma and inhibition by anti-epidermal growth factor receptor treatments. Cancer Res 2001 Sep 1; 61(17): 6500–10PubMed

17.

Albanell J, Rojo F, Averbuch S, et al. Pharmacodynamic studies of the epidermal growth factor receptor inhibitor ZD1839 in skin from cancer patients: histopathologic and molecular consequences of receptor inhibition. J Clin Oncol 2002 Jan 1; 20(1): 110–24PubMedCrossRef

18.

Budillon A, Di Gennaro E, Barbarino M, et al. ZD1839, an epidermal growth factor receptor tyrosine kinase inhibitor, upregulates P27(KIP1) inducing G1 arrest and enhancing the antitumor effect of interferon alpha. 91st Annu Meet Am Assoc Cancer Res 2000 Mar; 41: 773 (abstract no. 4910)

19.

Ohmori T, Yamaoka T, Nishio K, et al. ZD1839 (‘Iressa’) enhances TNFa-induced apoptotic cell death by inhibition of the Akt/NF-κB pathway in human non-small cell lung cancer PC-9 cells. 93rd Annu Meet Am Assoc Can Res 2002 Mar; 43: 335 (abstract no. 1663)

20.

Mandal M, Adam L, Wang R-A, et al. Inhibition of p21-activated kinase 1, directional cell motility and invasion of growth-factor-activated human cancer cells by the selective epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) ZD1839 (’Iressa’). 93rd Annu Meet Am Assoc Can Res 2002 Mar; 43: 157 (abstract no. 786)

21.

Hirata A, Ogawa S, Kometani T, et al. ZD1839 (Iressa) induces antiangiogenic effects through inhibition of epidermal growth factor receptor tyrosine kinase. Cancer Res 2002 May 1; 62(9): 2554–60PubMed

22.

Ciardiello F, Caputo R, Bianco R, et al. Inhibition of growth factor production and angiogenesis in human cancer cells by ZD1839 (Iressa), a selective epidermal growth factor receptor tyrosine kinase inhibitor. Clin Cancer Res 2001 May; 7(5): 1459–65PubMed

23.

Raben D, Helfrich B, Phistry M, et al. ZD1829 (’Iressa’), an EGFR-TKI, potentiates radiation/chemotherapy cytotoxicity in human non-small cell lung cancer cell lines. American Association of Cancer Research Special Conference in Cancer Research; 2000 Nov 6–11: Amsterdam

24.

Raben D, Helfrich BA, Chan D, et al. ZD1839, a selective epidermal growth factor receptor tyrosine kinase inhibitor, alone and in combination with radiation and chemotherapy as a new therapeutic strategy in non-small cell lung cancer. Semin Oncol 2002 Feb; 29 (1 Suppl. 4): 37–46PubMedCrossRef

25.

Naruse I, Ohmori T, Ao Y, et al. Antitumor activity of the selective epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) Iressa (ZD1839) in an EGFR-expressing multidrug-resistant cell line in vitro and in vivo. Int J Cancer 2002 Mar 10; 98(2): 310–5PubMedCrossRef

26.

Ohmori T, Ao Y, Yamaoka T, et al. ZD1839 (Iressa) enhances TNF-alpha-induced apoptotic cell death in human non-small cell lung cancer PC-9 cells. 92nd Annu Meet Am Assoc Can Res 2001 Mar; 42: 852 (abstract no. 4571)

27.

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 May; 6(5): 2053–63PubMed

28.

Sirotnak FM, Zakowski MF, Miller VA, et al. Efficacy of cytotoxic agents against human tumor xenografts is markedly enhanced by coadministration of ZD1839 (Iressa), an inhibitor of EGFR tyrosine kinase. Clin Cancer Res 2000 Dec; 6(12): 4885–92PubMed

29.

She Y, Lee F, Haimovitz-Friedman A, et al. The selective epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) ZD1839 (’Iressa’) enhances radiation sensitivity of human tumor xenografts in nude mice. 93rd Annu Meet Am Assoc Can Res 2002 Mar; 43: 786 (abstract no. 3895)

30.

Swaisland H, Stafford L, Laight A, et al. Pharmacokinetics and tolerability of the orally active selective epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 in healthy volunteers. Clin Pharmacokinet 2001; 40(4): 297–306PubMedCrossRef

31.

AstraZeneca. Single dose oral pharmacokinetics of ZD1839 (Data on file). 2002

32.

Ranson M, Hammond LA, Ferry D, et al. ZD1839, a selective oral epidermal growth factor receptor-tyrosine kinase inhibitor, is well tolerated and active in patients with solid, malignant tumors: results of a phase I trial. J Clin Oncol 2002 May 1; 20(9): 2240–50PubMedCrossRef

33.

Uejima H, Nakagawa K, Fukuoka M, et al. A phase I intermittent dose-escalation trial of ZD1839 (Iressa TM) in Japanese patients with solid tumors. Ann Oncol 2000; 11 Suppl. 4: 110–1 (plus poster)

34.

Swaisland H, Smith RP, Farebrother J, et al. The effect of the induction and inhibition of CYP3A4 on the pharmacokinetics of single oral doses of ZD1839 (’Iressa’), a selective epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), in healthy male volunteers. 38th Proc Am Soc Clin Oncol 2002 May; 21 (Pt 1 of 2) (abstract no. 328)

35.

Twelves C, Whte J, Harris A, et al. A phase I pharmacokinetic and tolerability trial of ZD1839 (Iressa) in hepatically impaired patients with solid tumours. 38th Proc Am Soc Clin Oncol 2002 May; 21 (Pt 1): 85a (abstract no. 339)

36.

Miller AB, Hoogstraten B, Staquet M, et al. Reporting results of cancer treatment. Cancer 1981 Jan 1; 47(1): 207–14PubMedCrossRef

37.

Baselga J, Herbst R, LoRusso P, et al. Continuous adminstration of ZD1839 (Iressa), a novel oral epidermal growth factor tyrosine kinase inhibitor (EGFR-TKI), in patients with five selected tumor types: evidence of activity and good tolerability. 36th Proc Am Soc Clin Oncol 2000 May 20; 19: 177 (abstract no. 1188)

38.

Fukuoka M, Yano S, Giaccone G, et al. Final results from a phase II trial of ZD1839 (’Iressa’) for patients with advanced non-small-cell lung cancer (IDEAL 1). 38th Proc Am Soc Clin Oncol 2002 May; 21(Pt 1 of 2): 298a (abstract no. 1188)

39.

Kris MG, Natale RB, Hebst RS, et al. A phase II trial of ZD1839 (’Iressa’) in advanced non-small cell lung cancer (NSCLC) patients who had failed platinum- and docetaxel-based regimens (IDEAL 2). 38th Proc Am Soc Clin Oncol 2002 May; 21 (Pt 1 of 2): 292 (abstract no. 1166)

40.

Natale RB, Skarin A, Maddox A-M, et al. Improvement in symptoms and quality of life for advanced non-small-cell lung cancer patients receiving ZD1839 (’Iressa’) in IDEAL 2 [plus poster]. 38th Proc Am Soc Clin Oncol 2002 May; 21(Pt 1 of 2): 292

41.

Douillard J-Y, Giaccone G, Horai T, et al. Improvement in disease-related symptoms and quality of life in patients with advanced non-small-cell lung cancer (NSCLC) treated with ZD 1839 (’Iressa’) IDEAL 1 [plus poster]. 38th Proc Am Soc Clin Oncol 2002 May; 21 (Pt 1 of 2): 299a (abstract no. 1195)

42.

AstraZeneca. Iressa® Tablets 250: Anti-cancer drug/epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (Gefitinib tablets). 2002

43.

AstraZeneca. Iressa (gefitinib): first approval world-wide for advanced non-small cell lung cancer [media release]. 2002

44.

Miller VA, Johnson D, Heelan RT, et al. A pilot trial demonstrates the safety of ZD1839 (Iressa), an oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), in combination with carboplatin and paclitaxel in previously untreated advanced non-small cell lung cancer. 37th Proc Am Soc Clin Oncol 2001 May 1; 20: 326 (abstract no. 1301 plus poster)

45.

Gonzalez-Larriba JL, Giaccone G, van Oosterom A, et al. ZD 1839 (’Iressa’) in combination with gemcitabine and cisplatin in chemonaive patients with advanced solid tumors: final results of a phase I trial. 38th Proc Am Soc Clin Oncol 2002 May; 21(Pt 1): 95a (abstract no. 376)

46.

Iressa fails in NSCLC combination trials. Scrip 2002 Aug 23; 2775: 21

Titel: Gefitinib
verfasst von: Christine R. Culy
Diana Faulds
Publikationsdatum: 01.10.2002
Verlag: Springer International Publishing
Erschienen in: Drugs / Ausgabe 15/2002
Print ISSN: 0012-6667
Elektronische ISSN: 1179-1950
DOI: https://doi.org/10.2165/00003495-200262150-00008

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

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Gefitinib

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Live-Webinar "Urologie und Sexualmedizin in der Praxis"

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