Gefitinib as a first-line therapy of advanced or metastatic adenocarcinoma of the lung in never-smokers.
OBJECTIVE
A subset of patients with adenocarcinoma of the lung who had never smoked cigarettes showed excellent tumor responses to gefitinib therapy. To evaluate the efficacy of gefitinib as a first-line therapy in this subgroup of patients, we conducted a phase II study.


METHODS
Eligible patients had no smoking history, stage IIIB or IV adenocarcinoma, Eastern Cooperative Oncology Group performance status 0 to 2, and adequate organ functions. Treatment consisted of daily oral administration ofF 250 mg gefitinib for 28 days until disease progression. Responses were assessed after every two cycles of therapy.


RESULTS
Of 37 patients enrolled, 36 were assessed for response. Twenty-five patients (69%) had partial response, 4 (11%) had stable disease, and 7 (19%) had progressive disease. Of 10 patients with evaluable brain metastases, 7 had objective responses in both intracranial and extracranial lesions, 1 had stable disease in the brain and dramatic response in the extracranial lesions, and 2 had progressive disease in both sites. After a median follow-up of 48 weeks (range, 4-70 weeks), 26 patients had disease progression, with median progression-free survival of 33 weeks, and 9 patients died, all due to disease progression. The median survival time has not been reached yet but the estimated 1-year survival rate was 73%. Common toxicities were skin rash and mild diarrhea but there was no significant hematologic toxicity.


CONCLUSIONS
Gefitinib showed very dramatic antitumor activity, even in the brain, with unprecedented survival outcome in never-smoker adenocarcinoma patients. These data support the use of gefitinib as a first-line therapy in this particular subgroup.
Lee
Dae Ho
DH
Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, South Korea.
Han
Ji-Youn
JY
Lee
Hong Gi
HG
Lee
Jae Jin
JJ
Lee
Eun Kyoung
EK
Kim
Hyae Young
HY
Kim
Hark Kyun
HK
Hong
Eun Kyung
EK
Lee
Jin Soo
JS
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000517:prevention & control / Q000556:secondary; D018450:Disease Progression; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D005500:Follow-Up Studies; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D012871:Skin Diseases / Q000139:chemically induced; D012907:Smoking; D016019:Survival Analysis; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D011799:Quinazolines; D000077156:Gefitinib