EGFR野生型肺腺癌患者一线化疗方案选择影响因素分析

Current situation and comparison of different first-line chemotherapy regimens in patients with advanced EGFR wild type lung adenocarcinoma

目的晚期肺癌一线化疗方案的有效率无明显差异,而在不良反应和药物经济学方面存在明显区别。本研究探讨晚期表皮生长因子受体(epidermal growth factor receptor,EGFR)野生型肺腺癌患者一线化疗方案应用状况并分析其原因。方法回顾性分析广州医科大学附属第一医院2009-12-01-2014-11-30收治的738例晚期EGFR野生型肺腺癌患者5种不同一线方案应用状况和影响因素,观察其近期疗效和不良反应。结果临床常用5种不同一线方案的患者例数分别为:吉西他滨含铂双药(GP组)358例,紫杉醇含铂双药(TP组)157例,多西他赛含铂双药(DP组)99例,培美曲塞含铂双药(PP组)93例,长春瑞滨含铂双药(NP组)31例。5组之间疗效差异无统计学意义,仅PP方案的疾病控制率较其他4个方案为优,χ2=4.01,P=0.038。5种方案不良反应:NP方案在3级以上白细胞减少方面明显高于其他方案,χ2=3.33,P=0.042;TP和DP方案在口腔炎、周围神经炎、3级及以上脱发的发生率方面明显高于其他方案,均P<0.05;GP方案而在血小板减少及谷丙转氨酶升高方面明显高于其他方案,χ2=3.21,P=0.043;PP方案在乏力方面明显高于其他方案,χ2=3.93,P=0.041;而5种方案在贫血、恶心、呕吐、腹泻、血肌酐升高和皮疹不良反应发生率差异无统计学意义。5种不同方案过去5年使用比例由高到低分别为,GP 48.51%>TP 21.27%>DP 13.41%>PP12.60%>NP 4.20%,这与5位制定化疗方案的主任医师对5个不同一线方案的平均评分排序完全一致。方案选择具体原因分析提示不良反应、使用便捷性、经济原因、医保政策4个因素是影响方案选择的主要原因,而疗效因素由于其本身差异并不明显,故并非是影响方案选择的主要原因。NP方案由于其不良反应和使用便捷性评分较低而总评分最低,而GP方案由于各方面均无明显劣势而总评分最高。结论过去5年晚期EGFR野生型肺腺癌患者常用的5种一线方案使用率顺序依次为GP>TP>DP>NP>PP。5种方案疗效未见明显差异,并非是影响方案选择的主要原因。方案的选择与制定方案的具体医生推荐有明显相关性,而具体原因主要集中在不良反应、使用便捷性、经济原因和医保政策4个因素。

OBJECTIVE There are no significant differences in the effective rate of advanced lung cancer first-line chemotherapy regimens, but exists significant difference in adverse reactions and drug economics, we investigate the application status of first-line chemotherapy in patients with advanced EGFR wild-type lung adenocarcinoma in clinical practice and analyze the reasons. METHODS A retrospective analysis of the actual situation and its influence factors in our hospital in the past five years in 827 advanced EGFR wild-type lung adenocarcinoma patients with different first-line chemotherapy was performed. At the same time, a preliminary influencing factors analysis was considered. The near future curative effect and adverse reactions were observed. RESULTS The number of patients in clinical commonly used five different first-line programs were： GP 358, TP 157, DP 99, PP 93, NP 31. There were no significant differences of the objective response rate for five different kinds of first-line chemotherapy, only the disease or control rate of PP scheme was better than that of the other four schemes, χ^2 =4.01, P〈0. 038. Adverse reaction of five scheme had obvious difference, in which the NP scheme in the above grade 3 leueopenia was significantly higher than that of other scheme,χ^2= 3.33, P= 0. 042. TP and DP scheme was significantly higher than those of other schemes in stomatitis, peripheral neuritis, 3 level and above of alopecia,all P values were less than 0.05. GP scheme in thrombocytopenia and elevated alanine aminotransferase was significantly higher than that of other scheme,χ^2 = 3, 21, P= 0. 043. PP scheme was significantly higher than that of other schemes in the weak, χ^2= 3.93,P= 0,041. There were no significant differences of the rate of anemia, nausea, vomiting, diarrhea, blood creatinine, rash of reaction in the five schemes. For five different schemes, in the past five years the percentages of regimens used for treatment respectively were GP 48.51%, TP 21.27%, DP 13. 41%, PP 12. 60%, NP 4. 20%. These ordering was completed consistent with average score of 5 different first-line schemes given by 5 different physicians. Scheme selection of specific reasons analysis showed four factors, such as adverse reactions, the convenience, the economic reason and the medical insurance policy were the main reason that affected the scheme selection. But the objective response rate was not obvious difference. It was not the main reason affecting the selection of schemes. The NP scheme got the lowest score because of its adverse reaction and inconvenient use. The GP program got the highest score because of its no obvious disadvantages. CONCLUSIONS In wild type EGFR of advanced lung adenocarcinoma patients, the percentages of five kinds of commonly used first-line chemotherapy in use over the past five years respectively were GP, TP, DP, NP, PP. There was significant correlation between specific doctors choose the different programs and the formulation of the recommended scheme, and the specific reason mainly concentrated in the four factors： adverse reactions, use convenience, economic reasons and the medical insurance policy, but the objective response rate was not the main factor.