TY - JOUR
T1 - Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer
T2 - A phase III trial - INTACT 1
AU - Giaccone, Giuseppe
AU - Herbst, Roy S.
AU - Manegold, Christian
AU - Scagliotti, Giorgio
AU - Rosell, Rafael
AU - Miller, Vincent
AU - Natale, Ronald B.
AU - Schiller, Joan H.
AU - Von Pawel, Joachim
AU - Pluzanska, Anna
AU - Gatzemeier, Ulrich
AU - Grous, John
AU - Ochs, Judith S.
AU - Averbuch, Steven D.
AU - Wolf, Michael K.
AU - Rennie, Pamela
AU - Fandi, Abderrahim
AU - Johnson, David H.
PY - 2004
Y1 - 2004
N2 - 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 II 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/m2 on day 1 and gemcitabine 1,250 mg/m2 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. 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.
AB - 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 II 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/m2 on day 1 and gemcitabine 1,250 mg/m2 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. 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.
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U2 - 10.1200/JCO.2004.08.001
DO - 10.1200/JCO.2004.08.001
M3 - Article
C2 - 14990632
AN - SCOPUS:1542503746
SN - 0732-183X
VL - 22
SP - 777
EP - 784
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 5
ER -