Sex difference in the influence of smoking status on the responsiveness to gefitinib monotherapy in adenocarcinoma of the lung: Okayama Lung Cancer Study Group experience
- 97 Downloads
Gefitinib is effective in patients with lung adenocarcinoma. Smoking status also affects the responsiveness to gefitinib, but it has not been fully evaluated whether a sex difference exists in the influence of smoking on the efficacy of gefitinib in patients with lung adenocarcinoma.
We reviewed the clinical records of 260 Japanese patients with lung adenocarcinoma who received gefitinib therapy (250 mg/day), and whose smoking status was known. Tumour response and survival were evaluated and stratified by smoking status and gender.
Among the 260 patients, 157 were male (60%). Median pack-years was 40 (range 8–160) and 23 (range 1–74) in male and female smokers, respectively. Objective response was observed in 62 (23.8%) of the 260 patients, and 1-year overall survival and progression-free survival were 45.1 and 24.3%, respectively. Multivariate analysis revealed that smoking status (pack-years) was an independent predictive factor for response to gefitinib [odds ratio (OR) = 0.971, 95% confidence interval (CI) = 0.947–0.995; P = 0.0159] in male patients, but not in female patients (OR = 0.999, 95%CI = 0.957–1.042). Additionally, pack-years significantly influenced the overall survival in males (hazard ratio = 1.010; 95%CI = 1.002–1018, P = 0.0169), while differential survival of females was not significantly predicted by this factor (P = 0.7639).
In male patients with lung adenocarcinoma, cumulative smoking significantly affected response and survival following gefitinib treatment, while in female patients, responsiveness to gefitinib was independent of smoking status. These results suggest that the influence of smoking habit on responsiveness to gefitinib is gender specific.
KeywordsGefitinib Gender Non-small-cell lung cancer Objective response Smoking status
We thank Drs. Tadashi Maeda, Atsuko Ogino, Shigeki Umemura, Keiichi Fujiwara, Toshiyuki Kozuki, Toshiaki Okada, Akiko Hisamoto, Naoyuki Nogami, Ichiro Takata, Hideki, Hiroaki Miyamoto and Shingo Harita for their support, data provision, and comments on the analysis.
Conflict of interest statement
- Fukuoka M, Yano S, Giaccone G, Tamura T, Nakagawa K, Douillard JY et al (2003) A multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small cell lung cancer (The IDEAL 1 Trial). J Clin Oncol 21:2237. doi: 10.1200/JCO.2003.10.038 PubMedCrossRefGoogle Scholar
- Hotta K, Matsuo K, Ueoka H, Kiura K, Tabata M, Tanimoto M (2004b) Addition of platinum compounds to a new agent in patients with advanced non-small-cell lung cancer: a literature based meta-analysis of randomised trials. Ann Oncol 15:1782–1789. doi: 10.1093/annonc/mdh476 PubMedCrossRefGoogle Scholar
- Hotta K, Kiura K, Toyooka S, Takigawa N, Soh J, Fujiwara Y et al (2007) Clinical significance of epidermal growth factor receptor gene mutations on treatment outcome after first-line cytotoxic chemotherapy in Japanese patients with non-small-cell lung cancer. J Thorac Oncol 2:632–637. doi: 10.1097/JTO.0b013e318074bc0d PubMedCrossRefGoogle Scholar
- Hotta H, Kiura K, Takigawa N, Fujiwara Y, Tabata M, Ueoka H et al. (2008) Association of the benefit from gefitinib monotherapy with smoking status in Japanese patients with non-small-cell lung cancer. Lung Cancer (in press)Google Scholar
- Kaiser U, Hofmann J, Schilli M, Wegmann B, Klotz U, Wedel S, et al. (1996) Steroid-hormone receptors in cell lines and tumor biopsies of human lung cancer. Int J Cancer 67:357–364. doi :10.1002/(SICI)1097-0215(19960729)67:3<357::AID-IJC9>3.0.CO;2-QGoogle Scholar
- Matsuo K, Ito H, Yatabe Y, Hiraki A, Hirose K, Wakai K et al (2006) Risk factors differ for non-small-cell lung cancers with and without EGFR mutation: assessment of smoking and sex by a case-control study in Japanese. Cancer Sci 98:96–101. doi: 10.1111/j.1349-7006.2006.00347.x CrossRefGoogle Scholar
- Non-Small Cell Lung Cancer Collaborative Group (1995) Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomized clinical trials. BMJ 311:899–909Google Scholar
- Thatcher N, Chang A, Parikh P, Rodrigues Pereira J, Ciuleanu T, von Pawel J et al (2005) Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet 366:1527–1537. doi: 10.1016/S0140-6736(05)67625-8 PubMedCrossRefGoogle Scholar