Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: A phase III trial-INTACT1 Journal Article


Authors: Giaccone, G.; Herbst, R. S.; Manegold, C.; Scagliotti, G.; Rosell, R.; Miller, V.; Natale, R. B.; Schiller, J. H.; Von Pawel, J.; Pluzanska, A.; Gatzemeier, M.; Grous, J.; Ochs, J. S.; Averbuch, S. D.; Wolf, M. K.; Rennie, P.; Fandi, A.; Johnson, D. H.
Article Title: Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: A phase III trial-INTACT1
Abstract: Purpose: The purpose of this study was to determine whether the addition of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib (Iressa, ZD1839; AstraZeneca, Wilmington, DE) to standard first-line gemcitabine and cisplatin provides clinical benefit over gemcitabine and cisplatin alone in patients with advanced or metastatic non-small-cell lung cancer (NSCLC). Gefitinib has demonstrated encouraging efficacy in advanced NSCLC in phase 11 trials in pretreated patients, and a phase I trial of gefitinib in combination with gemcitabine and cisplatin showed favorable tolerability. Patients and Methods: This was a phase III randomized, double-blind, placebo-controlled, multicenter trial in chemotherapy-naive patients with unresectable stage III or IV NSCLC. All patients received up to six cycles of chemotherapy (cisplatin 80 mg/m(2) on day 1 and gemcitabine 1,250 mg/m(2) on days 1 and 8 of the 3-week cycle) plus either gefitinib 500 mg/d, gefitinib 250 mg/d, or placebo. Daily gefitinib or placebo was continued until disease progression. End points included overall survival (primary), time to progression, response rates, and safety evaluation. Results: A total of 1,093 patients were enrolled. There was no difference in efficacy end points between the treatment groups: for the gefitinib 500 mg/d, gefitinib 250 mg/d, and placebo groups, respectively, median survival times were 9.9, 9.9, and 10.9 months (global ordered log-rank [GOLrank] P =.4560), median times to progression were 5.5, 5.8, and 6.0 months (GOLrank; P =.7633), and response rates were 49.7%, 50.3%, and 44.8%. No significant unexpected adverse events were seen. (C) 2004 by American Society of Clinical Oncology. Conclusion: Gefitinib in combination with gemcitabine and cisplatin in chemotherapy-naive patients with advanced NSCLC did not have improved efficacy over gemcitabine and cisplatin alone. The reasons for this remain obscure and require further preclinical testing.
Keywords: chemotherapy; inhibitor; tumors; tyrosine kinase; trial; efficacy; growth-factor receptor; iressa
Journal Title: Journal of Clinical Oncology
Volume: 22
Issue: 5
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2004-03-01
Start Page: 777
End Page: 784
Language: English
ACCESSION: WOS:000189380900006
DOI: 10.1200/jco.2004.08.001
PROVIDER: wos
PUBMED: 14990632
Notes: Article -- Source: Wos
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MSK Authors
  1. Vincent Miller
    259 Miller