Skip to main content
SpringerLink
Log in

Gefitinib

A Review of its Use in the Treatment of Locally Advanced/Metastatic Non-Small Cell Lung Cancer

  • Adis Drug Evaluation
  • Published:
Drugs Aims and scope Submit manuscript

Summary

Abstract

Gefitinib (Iressa™) is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that offers treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC), in particular in those who are harbouring EGFR mutations. In a large phase III trial (IPASS) in chemotherapy-naive Asian patients with adenocarcinoma who were never smokers or former light smokers, oral gefitinib was more effective than carboplatin plus paclitaxel in prolonging progression-free survival (PFS). In a prespecified subgroup analysis, EGFR-mutation-positive status was associated with a positive response to gefitinib treatment. Furthermore, a trial in chemotherapy-naive patients with NSCLC that was restricted to those with EGFR mutations found that gefitinib recipients had significantly longer PFS than carboplatin plus paclitaxel recipients. In large phase III trials (INTEREST, V-15-32) in unselected, previously treated patients, the overall survival (OS) in gefitinib recipients was noninferior to, or not significantly different from, that of docetaxel recipients. In a placebo-controlled trial in previously treated patients (ISEL), pre-planned subgroup analyses in Asian patients and non-smokers showed that in these subgroups gefitinib prolonged OS, and that EGFR biomarkers predicted a positive response to gefitinib. Gefitinib was also associated with greater improvements in quality of life (QOL) in both chemotherapy-naive and previously treated patients. A head-to-head trial of gefitinib versus erlotinib in EGFR-mutation-positive patients would help position gefitinib relative to erlotinib in this population. Further research is also required to identify factors associated with non-response to EGFR-tyrosine-kinase inhibitors in EGFR-mutation-positive patients. Gefitinib was a generally well tolerated treatment, with rash and diarrhoea being the most common treatment-emergent adverse events. Interstitial lung disease (ILD) is a serious co-morbidity of NSCLC associated with gefitinib and other cancer treatments; ILD-type events occurred with an overall incidence of ≈1% in gefitinib recipients participating in clinical trials, and were more common in Asian patients. Notably, gefitinib was associated with significantly fewer haematological and neurological adverse effects than comparator chemotherapy regimens. Gefitinib as monotherapy is an effective treatment for patients with locally advanced or metastatic NSCLC with EGFR mutations.

Pharmacological Properties

The presumed mechanism of action of gefitinib is through inhibition of EGFR tyrosine kinase, thereby blocking EGFR downstream signalling processes that activate cell proliferation, cell migration, angiogenesis and cell survival. Inhibitory effects on downstream EGFR processes occur at concentrations well below those achieved at the recommended clinical dosage. Mutations in the kinase domain of EGFR are correlated with sensitivity to gefitinib and other EGFR-tyrosine-kinase inhibitors.

After oral administration, gefitinib is relatively slowly absorbed, with a time to peak concentration of 3–7 hours. In healthy adults, for single doses up to and including 250 mg, increases in systemic exposure to gefitinib are dose-proportional. The oral bioavailability of gefitinib in patients with solid tumours is 59%. Gefitinib also penetrates tumour tissues, reaching high concentrations 42- to 60-fold those in plasma. Gefitinib is metabolized by hepatic cytochrome P450 (CYP) enzymes, predominantly CYP3A4, and is excreted chiefly via the gastrointestinal tract, with an elimination half-life of 41 hours. Although gefitinib has no clinically important inhibitory effect on CYP enzymes, caution is required when coadministering with potent CYP3A4 inhibitors or inducers.

Therapeutic Efficacy

In the IPASS trial (n = 1217, conducted in Asia), which included chemotherapy-naive patients selected for likely responsiveness to EGFR-tyrosine-kinase inhibitors (never smokers or former light smokers, adenocarcinoma histology), gefitinib 250mg/day was significantly more effective than carboplatin plus paclitaxel in terms of PFS (primary endpoint), with a hazard ratio (HR) of 0.74 (95% confidence interval [CI] 0.65, 0.85). In pre-planned subgroup analyses in patients with and without EGFR mutations (n = 437), patients with EGFR mutations had longer PFS with gefitinib than with carboplatin plus paclitaxel treatment (HR 0.48; 95% CI 0.36, 0.64; p < 0.001), while patients without EGFR mutations had longer PFS with carboplatin plus paclitaxel than with gefitinib treatment (HR 2.85; 95% CI 2.05, 3.98; p < 0.001). In the overall population, gefitinib recipients also had a significantly higher objective response rate (ORR) [p < 0.001] and QOL improvement rate (p ≤ 0.01) than carboplatin plus paclitaxel recipients. In the EGFR-mutation-positive subgroup, ORR and QOL improvement rates were also significantly higher (p < 0.001) in gefitinib recipients than carboplatin plus paclitaxel recipients, whereas in the EGFR-mutation-negative subgroup, carboplatin plus paclitaxel was more effective (p ≤ 0.01) than gefitinib for these endpoints. Consistent with IPASS, in a trial conducted by the North East Japan Study Group (Study 002) that was restricted to chemotherapy-naive patients with EGFR mutations, gefitinib was more effective than carboplatin plus paclitaxel according to PFS and the ORR.

In the ISEL trial (n = 1692, conducted globally) in unselected patients with stage III or IV NSCLC who were highly refractory to their most recent chemotherapy, OS (primary endpoint) was not significantly different in gefitinib 250mg/day versus placebo recipients; the HR was 0.89 (95% CI 0.77, 1.02). However, in preplanned subgroup analyses, OS was significantly longer in gefitinib recipients than placebo recipients in never smokers and patients of Asian ethnicity. Furthermore, a high EGFR gene copy number was associated with clinical benefit from gefitinib.

In previously treated patients, relative to docetaxel, gefitinib 250mg/day was noninferior for OS (primary endpoint) in the INTEREST trial (n = 1433, conducted globally) and did not differ significantly from docetaxel for this primary endpoint in the V-15-32 trial (n = 489, conducted in Japan). In addition, both trials showed significant benefits of gefitinib over docetaxel for secondary endpoints relating to QOL improvement and, in the V-15-32 trial, the ORR was higher in the gefitinib than the docetaxel treatment group. In INTEREST, there was no significant difference in OS between the gefitinib and docetaxel groups in patients with a high EGFR gene copy number (co-primary analysis). There was also no significant between-group difference in OS according to EGFR protein expression, EGFR-mutation or KRAS-mutation status in pre-planned subgroup analyses.

Tolerability

Gefitinib was generally well tolerated across all the clinical trials, with skin rashes and diarrhoea being the most common treatment-emergent adverse events. Compared with carboplatin plus paclitaxel and docetaxel regimens, gefitinib had significantly higher rates of skin adverse events. However, compared with carboplatin plus paclitaxel, gefitinib had significantly lower rates of nausea and vomiting, and haematological and neurological adverse events; compared with docetaxel, gefitinib had significantly lower rates of asthenia, and haematological and neurological adverse events. Few withdrawals from the trials were attributed to an adverse event and fewer than 6% of the patients died as a result of treatment-emergent adverse events. The most serious adverse events associated with gefitinib treatment are ILD-type events, which occur in ≈1% of patients overall, but appear to be more common in patients of Asian ethnic background (≈3–5%).

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

Table I
Table II
Table III
Table IV
Table V
Table VI
Fig. 1
Table VII

Similar content being viewed by others

References

  1. World Health Organization. Cancer [online]. Available from URL: http://www.who.int/mediacentre/factsheets/fs297/en/index.html [Accessed 2009 Apr 29]

  2. D’Addario G, Felip E. Non-small-cell lung cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up. ESMO Guidelines Working Group. Ann Oncol 2008 May; 19 Suppl. 2: ii39–40

    Article  PubMed  Google Scholar 

  3. Herbst RS, Heymach JV. Lung cancer. N Engl J Med 2008 Sep 25; 359(13): 1367–80

    Article  PubMed  CAS  Google Scholar 

  4. Pisters KM, Evans WK, Azzoli CG, et al. Cancer Care Ontario and American Society of Clinical Oncology adjuvant chemotherapy and adjuvant radiation therapy for stages I–IIIA resectable non small-cell lung cancer guideline. J Clin Oncol 2007 Dec 1; 25(34): 5506–18

    Article  PubMed  Google Scholar 

  5. Mountain CF. Revisions in the International System for Staging Lung Cancer. Chest 1997 Jun 1; 111(6): 1710–7

    Article  PubMed  CAS  Google Scholar 

  6. Herbst R, Bunn PA. Targeting the epidermal growth factor receptor in non-small cell lung cancer. Clin Cancer Res 2003 Dec 1;9: 5813–24

    PubMed  CAS  Google Scholar 

  7. Frampton JE, Easthope SE. Gefitinib: a review of its use in the management of advanced non-small-cell lung cancer. Drugs 2004; 64(21): 2475–92

    Article  PubMed  CAS  Google Scholar 

  8. European Medicines Agency. Iressa: summary of product characteristics [online]. Available from URL: http://www.emea.europa.eu/humandocs/PDFs/EPAR/iressa/emea-combined-h-1016-en.pdf [Accessed 2009 Aug 7]

  9. Herbst RS, Maddox AM, Rothenberg ML, et al. Selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 is generally well-tolerated and has activity in non-small-cell lung cancer and other solid tumors: results of a phase I trial. J Clin Oncol 2002 Sep 15; 20(18): 3815–25

    Article  PubMed  CAS  Google Scholar 

  10. Sugio K, Uramoto H, Ono K, et al. Mutations within the tyrosine kinase domain of EGFR gene specifically occur in lung adenocarcinoma patients with a low exposure of tobacco smoking. Br J Cancer 2006 Mar 27; 94(6): 896–903

    Article  PubMed  CAS  Google Scholar 

  11. Bell DW, Lynch TJ, Haserlat SM, et al. Epidermal growth factor receptor mutations and gene amplification in non-small-cell lung cancer: molecular analysis of the IDEAL/INTACT gefitinib trials. J Clin Oncol 2005 Nov 1; 23(31): 8081–92

    Article  PubMed  CAS  Google Scholar 

  12. Shigematsu H, Lin L, Takahashi T, et al. Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst 2005; 97(5): 339–46

    Article  PubMed  CAS  Google Scholar 

  13. Sato M, Shames DS, Gazdar AF, et al. A translational view of the molecular pathogenesis of lung cancer. J Thorac Oncol 2007; 2(4): 327–43

    Article  PubMed  Google Scholar 

  14. Linardou H, Dahabreh IJ, Bafaloukos D, et al. Somatic EGFR mutations and efficacy of tyrosine kinase inhibitors in NSCLC. Nat Rev Clin Oncol 2009; 6(6): 352–66

    Article  PubMed  CAS  Google Scholar 

  15. Baselga J, Rischin D, Ranson M, et al. Phase I safety, pharmacokinetic, and pharmacodynamic trial of ZD1839, a selective oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with five selected solid tumor types. J Clin Oncol 2002 Nov 1; 20(21): 4292–302

    Article  PubMed  CAS  Google Scholar 

  16. Wakeling AE, Guy SP, Woodburn JR, et al. ZD1839 (Iressa): an orally active inhibitor of epidermal growth factor signaling with potential for cancer therapy. Cancer Res 2002 Oct 15; 62(20): 5749–54

    PubMed  CAS  Google Scholar 

  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): 110–24

    Article  PubMed  CAS  Google Scholar 

  18. Cragg MS, Kuroda J, Puthalakath H, et al. Gefitinib-induced killing of NSCLC cell lines expressing mutant EGFR requires BIM and can be enhanced by BH3 mimetics. PLoS Med 2007 Oct; 4(10): 1681–9

    Article  PubMed  CAS  Google Scholar 

  19. Tanaka T, Munshi A, Brooks C, et al. Gefitinib radiosensitizes non-small cell lung cancer cells by suppressing cellular DNA repair capacity. Clin Cancer Res 2008 Feb 15; 14(4): 1266–73

    Article  PubMed  CAS  Google Scholar 

  20. Giaccone G, Iacona RB, Fandi A, et al. Epidermal growth factor receptor expression analysis in chemotherapy-naive patients with advanced non-small-cell lung cancer treated with gefitinib or placebo in combination with platinum-based chemotherapy. J Cancer Res Clin Oncol 2009 Mar; 135(3): 467–76

    Article  PubMed  CAS  Google Scholar 

  21. Herbst RS, Giaccone G, Schiller JH, et al. Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial — INTACT 2. J Clin Oncol 2004 Mar 1; 22(5): 785–94

    Article  PubMed  CAS  Google Scholar 

  22. Fukuoka M, Yano S, Giaccone G, et al. Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer. J Clin Oncol 2003 Jun 15; 21(12): 2237–46

    Article  PubMed  CAS  Google Scholar 

  23. Kris MG, Natale RB, Herbst RS, et al. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA 2003 Oct 22; 290(16): 2149–58

    Article  PubMed  CAS  Google Scholar 

  24. Tamura K, Okamoto I, Kashii T, et al. Multicentre prospective phase II trial of gefitinib for advanced non-small cell lung cancer with epidermal growth factor receptor mutations: results of the West Japan Thoracic Oncology Group trial (WJTOG0403). Br J Cancer 2008 Mar 11; 98(5): 907–14

    Article  PubMed  CAS  Google Scholar 

  25. Sugio K, Uramoto H, Onitsuka T, et al. Prospective phase II study of gefitinib in non-small cell lung cancer with epidermal growth factor receptor gene mutations. Lung Cancer 2009; 64(3): 314–8

    Article  PubMed  Google Scholar 

  26. Sequist LV, Martins RG, Spigel D, et al. First-line gefitinib in patients with advanced non-small-cell lung cancer harboring somatic EGFR mutations. J Clin Oncol 2008 May 20; 26(15): 2442–9

    Article  PubMed  CAS  Google Scholar 

  27. Inoue A, Kobayashi K, Usui K, et al. First-line gefitinib for patients with advanced non-small cell lung cancer harboring epidermal growth factor receptor mutations without indication for chemotherapy. J Clin Oncol 2009 Mar 20; 27(9): 1394–400

    Article  PubMed  CAS  Google Scholar 

  28. Costa DB, Kobayashi S, Tenen DG, et al. Pooled analysis of the prospective trials of gefitinib monotherapy for EGFR-mutant non-small cell lung cancers. Lung Cancer 2007 Oct; 58(1): 95–103

    Article  PubMed  Google Scholar 

  29. Swaisland HC, Smith RP, Laight A, et al. Single-dose clinical pharmacokinetic studies of gefitinib. Clin Pharmacokinet 2005; 44(11): 1165–77

    Article  PubMed  CAS  Google Scholar 

  30. Nakagawa K, Tamura T, Negoro S, et al. Phase I pharmacokinetic trial of the selective oral epidermal growth factor receptor tyrosine kinase inhibitor gefitinib (‘Iressa’, ZD1839) in Japanese patients with solid malignant tumors. Ann Oncol 2003 Jun; 14(6): 922–30

    Article  PubMed  CAS  Google Scholar 

  31. Swaisland HC, Cantarini MV, Fuhr R, et al. Exploring the relationship between expression of cytochrome P450 enzymes and gefitinib pharmacokinetics. Clin Pharmacokinet 2006; 45(6): 633–44

    Article  PubMed  CAS  Google Scholar 

  32. Swaisland HC, Ranson M, Smith RP, et al. Pharmacokinetic drug interactions of gefitinib with rifampicin, itraconazole and metoprolol. Clin Pharmacokinet 2005; 44(10): 1067–81

    Article  PubMed  CAS  Google Scholar 

  33. Rukazenkov Y, Speake G, Marshall G, et al. Epidermal growth factor receptor tyrosine kinase inhibitors: similar but different? Anticancer Drugs. Epub 2009 Aug 4

  34. AstraZeneca. A phase 1, open-label, dose-escalating study evaluating high-dose gefitinib (Iressa) on weekly and twice-weekly schedules in subjects with solid malignancies that are locally advanced, recurrent or metastatic [online]. Available from URL: http://astrazenecaclinicaltrials.com/_mshost2715844/content/content/resources/media/2958892/4441676 [Accessed 2009 Sep 7]

  35. Giaccone G, Herbst RS, Manegold C, et al. Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial — INTACT 1. J Clin Oncol 2004 Mar 1; 22(5): 777–84

    Article  PubMed  CAS  Google Scholar 

  36. Mok TS, Wu Y-L, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361(10): 947–57

    Article  PubMed  CAS  Google Scholar 

  37. Goss G, Ferry D, Wierzbicki R, et al. Randomized phase II study of gefitinib compared with placebo in chemotherapy-naive patients with advanced non-small-cell lung cancer and poor performance status. J Clin Oncol 2009 May; 27(13): 2253–60

    Article  PubMed  CAS  Google Scholar 

  38. Crinò L, Cappuzzo F, Zatloukal P, et al. Gefitinib versus vinorelbine in chemotherapy-naive elderly patients with advanced non-small-cell lung cancer (INVITE): a randomized, phase II study. J Clin Oncol 2008 Sep 10; 26(26): 4253–60

    Article  PubMed  Google Scholar 

  39. Kelly K, Chansky K, Gaspar LE, et al. Phase III trial of maintenance gefitinib or placebo after concurrent chemoradiotherapy and docetaxel consolidation in inoperable stage III non-small-cell lung cancer: SWOG S0023. J Clin Oncol 2008 May 20; 26(15): 2450–6

    Article  PubMed  CAS  Google Scholar 

  40. Hida T, Okamoto I, Kashii T, et al. Randomized phase III study of platinum-doublet chemotherapy followed by gefitinib versus continued platinum-doublet chemotherapy in patients (pts) with advanced non-small cell lung cancer (NSCLC): results of West Japan Thoracic Oncology Group trial (WJTOG) [abstract no. LBA8012]. 44th Annual Meeting of the American Society of Clinical Oncology; 2008 May 30–Jun 3; Chicago (IL)

  41. Kobayashi K, Inoue A, Maemondo M, et al. First-line gefitinib versus first-line chemotherapy by carboplatin (CBDCA) plus paclitaxel (TXL) in non-small cell lung cancer (NSCLC) patients (pts) with EGFR mutations: a phase III study (002) by North East Japan Gefitinib Study Group [abstract no. 8016]. J Clin Oncol 2009; 27 Suppl.; 15s. Plus poster presented at the 44th Annual Meeting of the American Society of Clinical Oncology; 2009 May 29–Jun 2; Orlando (FL)

    Article  Google Scholar 

  42. Thatcher N, Chang A, Parikh P, et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet 2005 Oct 29–Nov 4; 366(9496): 1527–37

    Article  PubMed  CAS  Google Scholar 

  43. Kim ES, Hirsh V, Mok T, et al. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet 2008 Nov 22; 372(9652): 1809–18

    Article  PubMed  CAS  Google Scholar 

  44. Maruyama R, Nishiwaki Y, Tamura T, et al. Phase III study, V-15-32, of gefitinib versus docetaxel in previously treated Japanese patients with non-small-cell lung cancer. J Clin Oncol 2008 Sep 10; 26(26): 4244–52

    Article  PubMed  CAS  Google Scholar 

  45. Lee D, Kim S, Park K et al. A randomized open-label study of gefitinib versus docetaxel in patients with advanced/metastatic non-small cell lung cancer (NSCLC) who have previously received platinum-based chemotherapy [abstract no. 8025]. J Clin Oncol 2008 May 20; 26 Suppl.: 430s. Plus poster presented at the 44th Annual Meeting of the American Society of Clinical Oncology; 2008 May 30–Jun 3; Chicago (IL)

    Google Scholar 

  46. Cufer T, Vrdoljak E, Gaafar R, et al. Phase II, open-label, randomized study (SIGN) of single-agent gefitinib (IRESSA) or docetaxel as second-line therapy in patients with advanced (stage IIIb or IV) non-small-cell lung cancer. Anticancer Drugs 2006 Apr; 17(4): 401–9

    Article  PubMed  CAS  Google Scholar 

  47. Natale RB, Bodkin D, Govindan R, et al. Vandetanib versus gefitinib in patients with advanced non-small-cell lung cancer: results from a two-part, double-blind, randomized phase II study. J Clin Oncol 2009 May 20; 27(15): 2523–9

    Article  PubMed  CAS  Google Scholar 

  48. Uhm JE, Sun JM, Lee SH, et al. Comparison of erlotinib (Tarceva™) versus gefitinib (Iressa®) as the second line therapy for the treatment of advanced non-small cell lung cancer patients: a randomized phase II trial [abstract no. A2.6]. 13th World Conference on Lung Cancer, International Association for the Study of Lung Cancer; 2009 Jul 31–Aug 4; San Francisco (CA)

  49. Hirsch FR, Varella-Garcia M, Bunn PA Jr, et al. Molecular predictors of outcome with gefitinib in a phase III placebo-controlled study in advanced non-small-cell lung cancer. J Clin Oncol 2006 Nov 1; 24(31): 5034–42

    Article  PubMed  CAS  Google Scholar 

  50. Chang A, Parikh P, Thongprasert S, et al. Gefitinib (IRESSA) in patients of Asian origin with refractory advanced non-small cell lung cancer: subset analysis from the ISEL study. J Thorac Oncol 2006 Oct; 1(8): 847–55

    Article  PubMed  Google Scholar 

  51. Shepherd FA, Douillard J-Y, Fukuoka M, et al. Comparison of gefitinib and docetaxel in patients with pretreated advanced non-small cell lung cancer: meta-analysis from four clinical trials [abstract no. 8011 plus poster]. 45th Annual Meeting of the American Society of Clinical Oncology; 2009 May 29–Jun 2; Orlando (FL)

  52. Forsythe B, Faulkner K. Overview of the tolerability of gefitinib (IRESSA) monotherapy: clinical experience in non-small-cell lung cancer. Drug Saf 2004; 27(14): 1081–92

    Article  PubMed  CAS  Google Scholar 

  53. Hotta K, Kiura K, Tabata M, et al. Interstitial lung disease in Japanese patients with non-small cell lung cancer receiving gefitinib: an analysis of risk factors and treatment outcomes in Okayama Lung Cancer Study Group. Cancer J 2005 Sep; 11(5): 417–24

    Article  PubMed  CAS  Google Scholar 

  54. Kudoh S, Kato H, Nishiwaki Y, et al. Interstitial lung disease in Japanese patients with lung cancer: a cohort and nested case-control study. Am J Respir Crit Care Med 2008 Jun 15; 177(12): 1348–57

    Article  PubMed  Google Scholar 

  55. Danson S, Blackhall F, Hulse P, et al. Interstitial lung disease in lung cancer: separating disease progression from treatment effects. Drug Saf 2005; 28(2): 103–13

    Article  PubMed  Google Scholar 

  56. National Institute for Clinical Excellence. The diagnosis and treatment of lung cancer [online]. Available from URL: http://www.nice.org.uk/nicemedia/pdf/cg024fullguideline.pdf [Accessed 2009 Jul 9]

  57. National Comprehensive Cancer Network. Clinical practice guidelines in oncology. Vol. 1 [online]. Available from URL: http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf [Accessed 2009 May 21]

  58. Noble J, Ellis PM, Mackay JA, et al. Second-line or subsequent systemic therapy for recurrent or progressive non-small cell lung cancer: a systematic review and practice guideline. J Thorac Oncol 2006 Nov; 1(9): 1042–58

    Article  PubMed  CAS  Google Scholar 

  59. Jett JR, Schild SE, Keith RL, et al. Treatment of non-small cell lung cancer, stage IIIB: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007 Sep; 132 (3 Suppl.): 266–76S

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Adis, a Wolters Kluwer Business, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore, Auckland, 0754, New Zealand

    Mark Sanford & Lesley J. Scott

Authors
  1. Mark Sanford
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lesley J. Scott
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mark Sanford.

Additional information

Various sections of the manuscript reviewed by: Y.-M. Chen, Chest Department, Taipei Veterans Hospital, Taipei, Taiwan; Q. Chu, Medical Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada; M. Davis, Division of Solid Tumor, Taussig Cancer Center, Cleveland Clinic, Cleveland, Ohio, USA; T.S. Mok, Department of Clinical Oncology, Sir YK Pao Centre for Cancer, Chinese University of Hong Kong, Hong Kong, China; K. Park, Division of Haematology/Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea; D. Tassinari, Oncology, City Hospital, Rimini, Italy.

Data Selection

Sources: Medical literature published in any language since 1980 on gefitinib in non-small cell lung cancer, identified using MEDLINE and EMBASE, supplemented by AdisBase (a proprietary database). Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.

Search strategy: MEDLINE, EMBASE and AdisBase search terms were ‘gefitinib’ and (‘non-small cell lung cancer’ or ‘NSCLC’). Searches were last updated 25 September 2009.

Selection: Studies in patients with non-small cell lung cancer who received gefitinib. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: Gefitinib, non-small cell lung cancer, epidermal growth factor receptor tyrosine kinase inhibitor, pharmacodynamics, pharmacokinetics, therapeutic use, tolerability.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sanford, M., Scott, L.J. Gefitinib. Drugs 69, 2303–2328 (2009). https://doi.org/10.2165/10489100-000000000-00000

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/10489100-000000000-00000

Keywords

Search

Navigation