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Gefitinib as a First-Line Therapy of Advanced or Metastatic Adenocarcinoma of the Lung in Never-Smokers

Authors' Affiliations: Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, South Korea

Requests for reprints: Jin Soo Lee, National Cancer Center, 809 Madu-dong, Ilsan-gu, Goyang, Gyeonggi, 411-769, South Korea. Phone: 82-31-920-1601; Fax: 82-31-920-1520; E-mail: jslee{at}ncc.re.kr.

Purpose: 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.

Experimental Design: 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.

Key Words: gefitinib • adenocarcinoma of the lung • never-smoker • Phase I to III Clinical Trials • Lung cancer • Tobacco

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