Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial) [corrected].
OBJECTIVE
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).


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 randomly assigned 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.


CONCLUSIONS
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 [corrected]
Fourth Department of Internal Medicine, Kinki University School of Medicine, 377-2 Ohnohigashi Osakasayama, Osaka 589, Japan. mfukuoka@med.kindai.ac.jp
Masahiro
M
Fukuoka
Seiji
S
Yano
Giuseppe
G
Giaccone
Tomohide
T
Tamura
Kazuhiko
K
Nakagawa
Jean-Yves
JY
Douillard
Yutaka
Y
Nishiwaki
Johan
J
Vansteenkiste
Shinzoh
S
Kudoh
Danny
D
Rischin
Richard
R
Eek
Takeshi
T
Horai
Kazumasa
K
Noda
Ichiro
I
Takata
Egbert
E
Smit
Steven
S
Averbuch
Angela
A
Macleod
Andrea
A
Feyereislova
Rui-Ping
RP
Dong
José
J
Baselga
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004311:Double-Blind Method; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors; D005260:Female; D000077156:Gefitinib; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011788:Quality of Life; D011799:Quinazolines / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D011799:Quinazolines; D004815:Epidermal Growth Factor; D011505:Protein-Tyrosine Kinases; D000077156:Gefitinib