Originally published as JCO Early Release 10.1200/JCO.2003.10.038 on May 14 2003

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

Masahiro Fukuoka, Seiji Yano, Giuseppe Giaccone, Tomohide Tamura, Kazuhiko Nakagawa, Jean-Yves Douillard, Yutaka Nishiwaki, Johan Vansteenkiste, Shinzoh Kudoh, Danny Rischin, Richard Eek, Takeshi Horai, Kazumasa Noda, Ichiro Takata, Egbert Smit, Steven Averbuch, Angela Macleod, Andrea Feyereislova, Rui-Ping Dong, José Baselga

From 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 Developmental Cancer Therapeutics, Melbourne, Australia; Mary Potter Oncology Centre, Pretoria, South Africa; Academic Hospital Free University, Amsterdam, the Netherlands; AstraZeneca, Wilmington, DE; AstraZeneca, Alderley Park, United Kingdom; and Vall d’Hebron University Hospital, Barcelona, Spain.

Address reprint requests to Masahiro Fukuoka, MD, Fourth Department of Internal Medicine, Kinki University School of Medicine, 377-2 Ohnohigashi Osakasayama, Osaka 589, Japan; email: mfukuoka{at}med.kindai.ac.jp.

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.

The authors wish to disclose the following conflicts of interest statement: José Baselga has been in receipt of a research grant from AstraZeneca and honoraria to attend advisory boards and to give talks on ZD1839; Johan Vansteenkiste has received honoraria from AstraZeneca to attend advisory boards; Jean Yves Douillard has received honoraria for participating in advisory boards or symposia; Giuseppe Giaccone has received honoraria and research grants; and Danny Rischin has been in receipt of honoraria and travel grants from AstraZeneca. Steven Averbuch, Angela Macleod, Andrea Feyereislova, and Rui-Ping Dong were employed by AstraZeneca at the time of study completion, and as such, may hold stock in the company. All other authors have nothing to declare.

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