Multi-Institutional Randomized Phase II Trial of Gefitinib for Previously Treated Patients With Advanced Non–Small-Cell Lung Cancer

American Society of Clinical Oncology (ASCO) - Tập 21 Số 12 - Trang 2237-2246 - 2003
Masahiro Fukuoka1,2,3,4,5,6,7,8,9, Seiji Yano1,2,3,4,5,6,7,8,9, Giuseppe Giaccone1,2,3,4,5,6,7,8,9, Tomohide Tamura1,2,3,4,5,6,7,8,9, Kazuhiko Nakagawa1,2,3,4,5,6,7,8,9, Jean‐Yves Douillard1,2,3,4,5,6,7,8,9, Yutaka Nishiwaki1,2,3,4,5,6,7,8,9, Johan Vansteenkiste1,2,3,4,5,6,7,8,9, Shinzoh Kudoh1,2,3,4,5,6,7,8,9, Danny Rischin1,2,3,4,5,6,7,8,9, Richard Eek1,2,3,4,5,6,7,8,9, Takeshi Horai1,2,3,4,5,6,7,8,9, Kazumasa Noda1,2,3,4,5,6,7,8,9, Ichiro Takata1,2,3,4,5,6,7,8,9, Egbert F. Smit1,2,3,4,5,6,7,8,9, Steven D. Averbuch1,2,3,4,5,6,7,8,9, Angela Macleod1,2,3,4,5,6,7,8,9, A. Feyereislova1,2,3,4,5,6,7,8,9, Rui-Ping Dong1,2,3,4,5,6,7,8,9, José Baselga1,2,3,4,5,6,7,8,9
1Academic Hospital, Free University, Amsterdam, The Netherlands
2Astrazeneca, Alderley Park, United Kingdom
3AstraZeneca, Wilmington, DE
4C.R.L.C.C. Rene Gauducheau, Saint-Herblain, France
5Centre for Developmental Cancer Therapeutics, Melbourne, Australia
6From the Kinki University School of Medicine, Osaka City University School of Medicine, and AstraZeneca, Osaka, Tokushima University School of Medicine, Tokushima, National Cancer Center, Central Hospital, and Japanese Foundation for Cancer Research, Tokyo, National Cancer Center, East Hospital, Chiba, Kanagawa Cancer Center, Yokohama, and National Shikoku Cancer Center, Matsuyama, Japan; C.R.L.C.C. Rene Gauducheau, Saint-Herblain, France; University Hospital Gasthuisberg, Leuven, Belgium; Centre for...
7Mary Potter Oncology Centre, Pretoria, South Africa
8University Hospital Gasthuisberg, Leuven, Belgium
9Vall d'Hebron University Hospital, Barcelona, Spain

Tóm tắt

Purpose: To evaluate the efficacy and tolerability of two doses of gefitinib (Iressa [ZD1839]; AstraZeneca, Wilmington, DE), a novel epidermal growth factor receptor tyrosine kinase inhibitor, in patients with pretreated advanced non–small-cell lung cancer (NSCLC). Patients and Methods: This was a randomized, double-blind, parallel-group, multicenter phase II trial. Two hundred ten patients with advanced NSCLC who were previously treated with one or two chemotherapy regimens (at least one containing platinum) were randomized to receive either 250-mg or 500-mg oral doses of gefitinib once daily. Results: Efficacy was similar for the 250- and 500-mg/d groups. Objective tumor response rates were 18.4% (95% confidence interval [CI], 11.5 to 27.3) and 19.0% (95% CI, 12.1 to 27.9); among evaluable patients, symptom improvement rates were 40.3% (95% CI, 28.5 to 53.0) and 37.0% (95% CI, 26.0 to 49.1); median progression-free survival times were 2.7 and 2.8 months; and median overall survival times were 7.6 and 8.0 months, respectively. Symptom improvements were recorded for 69.2% (250 mg/d) and 85.7% (500 mg/d) of patients with a tumor response. Adverse events (AEs) at both dose levels were generally mild (grade 1 or 2) and consisted mainly of skin reactions and diarrhea. Drug-related toxicities were more frequent in the higher-dose group. Withdrawal due to drug-related AEs was 1.9% and 9.4% for patients receiving gefitinib 250 and 500 mg/d, respectively. Conclusion: Gefitinib showed clinically meaningful antitumor activity and provided symptom relief as second- and third-line treatment in these patients. At 250 mg/d, gefitinib had a favorable AE profile. Gefitinib 250 mg/d is an important, novel treatment option for patients with pretreated advanced NSCLC.

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Tài liệu tham khảo

10.1159/000055386

10.1136/bmj.311.7010.899

Fossella FV, Lee JS, Hong WK: Management strategies for recurrent non-small cell lung cancer. Semin Oncol 24:455,1997–462,

10.1016/S0169-5002(01)00356-7

10.1200/JCO.2000.18.10.2095

10.1200/JCO.1997.15.8.2996

10.1016/1040-8428(94)00144-I

Rusch V, Baselga J, Cordon-Cardo C, et al: Differential expression of the epidermal growth factor receptor and its ligands in primary non-small cell lung cancers and adjacent benign lung. Cancer Res 53:2379,1993–2385,

10.1016/S0959-8049(96)00243-2

Pavelic K, Banjac Z, Pavelic J, et al: Evidence for a role of EGF receptor in the progression of human lung carcinoma. Anticancer Res 13:1133,1993–1137,

10.1038/bjc.1998.106

10.1016/S0163-7258(97)00052-1

Negoro S, Nakagawa K, Fukuoka M, et al: Final results of a phase I intermittent dose-escalation trial of ZD1839 (Iressa) in Japanese patients with various solid tumours. Proc Am Soc Clin Oncol 20:324a,2001, (abstr 1292)

10.1200/JCO.2002.10.112

Kris M, Herbst R, Rischin D, et al: Objective regressions in non-small cell lung cancer patients treated in phase I trials of oral ZD1839 (Iressa), a selective tyrosine kinase inhibitor that blocks the epidermal growth factor receptor (EGFR). Lung Cancer 29:72,2000, (suppl 1, abstr 231)

10.1007/BF00944177

10.1016/0169-5002(95)00450-F

10.1016/S0895-4356(01)00477-2

10.2307/2529712

Rowinsky EK: The pursuit of optimal outcomes in cancer therapy in a new age of rationally designed target-based anticancer agents. Drugs 60:1,2000–14, (suppl 1)

10.1200/JCO.2000.18.21.3722

10.1200/JCO.2000.18.12.2354

10.1053/sonc.2001.22540

Rusch V, Klimstra D, Venkatraman E, et al: Overexpression of the epidermal growth factor receptor and its ligand transforming growth factor α is frequent in resectable non-small cell lung cancer but does not predict tumor progression. Clin Cancer Res 3:515,1997–522,

Kris M, Natale RB, Herbst R, 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). Proc Am Soc Clin Oncol 21:292,2002, (abstr 1166)

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American Society of Clinical Oncology (ASCO)

Tập 21 Số 12

2237-2246

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