生活方式作为老年非小细胞肺癌患者吉非替尼治疗预测因素的研究

Investigation of life styles as response predictors of gefitinib in elder non-small cell lung cancer patients

目的探讨生活方式对老年非小细胞肺癌(NSCLC)患者吉非替尼治疗的影响。方法将组织学证实的ⅢB～Ⅳ的65岁及以上的老年NSCLC患者,分为吉非替尼敏感组和耐药组。吉非替尼敏感是指患者用吉非替尼治疗时获得客观疗效或疾病稳定时间持续4个月以上,或患者EGFR19、21外显子突变;耐药患者是指鳞癌患者,EGFR是野生型或用吉非替尼治疗4个月内出现疾病进展。调查问卷内容包括吸烟情况(吸烟者或二手烟者),职业接触,是否在家里做饭,居住地是城市还是农村。对于诊断时就是晚期的患者,患者的总生存时间从诊断时计算;对术后完全切除的患者生存时间从发现疾病复发时计算。结果 65岁及以上患者共114例,患者的平均年龄72.34岁(65～86岁),男女比例为66:48。腺癌患者96例,鳞癌患者17例。多因素回归分析显示,老年NSCLC患者吉非替尼的疗效不佳预测因素是鳞癌(风险比7.33,P=0.01),在家做饭(风险比15.19,P=0.000)。而女性(风险比0.19,P=0.000)、不吸烟(风险比0.11,P=0.000)、有职业暴露(风险比0.19,P=0.000)是吉非替尼治疗敏感的预测指标。吉非替尼敏感型42例,占36.84%,耐药型72例,占63.16%,两组患者的中位生存时间分别为28.39个月和10.84个月(P=0.0006)。有利于患者生存的预后因素是吉非替尼治疗有效(风险比0.25,P=0.016),不利于患者生存的预后因素是合并慢性肺部疾病(风险比6.32,P=0.01)。结论吉非替尼有效的预测因素是女性、不吸烟、有职业暴露,治疗无效的预测因素是鳞癌和在家做饭。吉非替尼治疗有效和无效患者的中位生存期有明显差异,但需要大样本调查进一步明确结果。

Objective To investigation the relationship between life-style risk factors and gefitinib efficacy in elder non-small cell lung cancer （NSCLC） patients. Methods NSCLC patients who were older than 65 years （65 years was included） were retrospectively investigated. Their diseases were histological proven and the clinical stage should be Ⅲ B-IV. Based on the clinical characteristics, they were divided into gefitinib sensitive or resistant groups. Gefitinib sensitive patients were defined as patients who had objective response or kept stable disease for more than 4 months during gefitinih treatment, and（or） patients whose epidermal growth factor receptor （EGFR） 19,21 exon were mutated. The resistant patient was defined as squamous cell carcinoma, EGFR wild genotype and（or） disease progressed within 4 months although patients had been treated with gefitinib. Tobacco exposure （smoker and second hand smoker, SHS）, occupational exposure （OE）, cooking Chinese food at home （CAH）, living area （city or rural area） were included in the self-designed questionnaire. The overall survival （OS） was calculated from the day of diagnosis for patient with advanced disease. For those patients who had completely resected disease with or without adjuvant chemotherapy, their OS was calculated from the day of recurrence determined. Results The mean age of the 114 patients was （72.34±5.16） years （65-86）. The male to female ratio of this group was 66：48. Seventeen patients had squamous cell cancer. In multivariate Logistic analysis, clinical features associated with negative response to gefitinib were squamous cell cancer （Odds ratio 7.33, P = 0.01）, cooking at home （CAH） （Odds ratio 15.19, P = 0.000）. Positive factors included female gender（Odds ratio 0.19, P = 0.000）, non smoker （Odds ratio 0.11, P = 0.000） and occupational exposure （Odds ratio 0.19, P = 0.000）. There were 42 patients who were sensitive to gefitinib and 72 patients who were resistant to the drug. The median overall survival of gefitinib sensitive and resistant groups were 28.39 months and 10.84 months respectively （P = 0.0006）. Cox analysis showed that gefitinib sensitive was the only independent prognostic factor for longer survival （Odds ratio 0.25, P = 0.016） and chronic lung disease was negative prognostic factor for survival （Odds ratio 6.32, P = 0.01）. Conclusions Investigation about older NSCLC patients has suggested that positive predictor factors of gefitinib efficacy on NSCLC patients are female, non smoker and occupational exposure and negative predictor factors are squamous cell cancer and cooking at home. There is significant difference in overall survival among patients who are sensitive to gefitinib or not. But the investigation is small in size and further studies are needed.