培美曲塞联合铂类一线治疗晚期非鳞非小细胞肺癌的临床观察

Clinical observation of efficacy and safety of pemetrexed plus platinum as the first–line chemotherapy with advanced non-squamous non-small cell lung cancer

背景与目的：晚期肺癌一线化疗有效率仅30%～40%，本研究旨在探讨培美曲塞联合铂类药物（卡铂或顺铂）治疗晚期非鳞非小细胞肺癌（non-small cell lung cancer，NSCLC）的疗效及不良反应。方法：121例非鳞NSCLC患者，给予培美曲塞联合铂类化疗：培美曲塞500 mg/m2第1天，静脉滴注，卡铂300 mg/m2，第1天，静脉滴注，每3周重复；或培美曲塞500 mg/m2，第1天，静脉滴注，顺铂70 mg/m2，第1天，静脉滴注，每3周重复。上述方案连用2-6个周期，至少2个周期评价疗效。主要观察终点是疾病控制率（disease control rate，DCR），其次是中位无进展生存时间（progression-free survival，PFS）、1年生存率和安全性。结果：全组可评价疗效121例，完全缓解（complete response，CR）1例，部分缓解（partial response， PR）44例，病情稳定（stable disease，SD）50例，疾病进展（progressive disease，PD）26例，客观有效率（objective response rate，ORR）为37.2%（45/121），DCR为78.5%（95/121），PFS为5.2个月（95%CI：4.4~6.0个月），1年生存率为59.0%。其中培美曲塞联合卡铂组ORR为38.3%（23/60），DCR为78.3%（47/60）， PFS为5.1个月（95%CI：3.8~6.4个月），1年生存率55.2%；培美曲塞联合顺铂组ORR为36.1%（22/61），DCR为78.7%（48/61），PFS为6.2个月（95%CI：4.3~8.1个月），1年生存率为62.5%。两组之间的ORR、DCR、PFS和1年生存率差异无统计学意义（P＞0.05）。主要不良反应为中性粒细胞和白细胞下降、乏力及胃肠道反应。结论：培美曲塞联合铂类药物一线治疗晚期非鳞NSCLC疗效确切，不良反应发生率低，耐受性较好。

Background and purpose：The effective rate of ifrst-line chemotherapy for advanced lung cancer is 30%-40%. The purpose of this study was to evaluate the efifcacy and adverse effects of pemetrexed combined with carboplatin or cisplatin in the treatment of patients with advanced non-squamous non-small cell lung cancer （NSCLC）. Methods：One hundrend and twenty-one patients with advanced non-squamous NSCLC were enrolled in this study and all of these patients had been conifrmed with pathology or cytology. Among the 121 cases, 60 cases were male and 61 were female, the median age was 59 years, adnenocarcinoma in 113 patients and large cell carcinoma in 8 patients. Combination regimen： patients received pemetrexed 500 mg/m2 on day 1 and carboplatin 300 mg/m2 or cisplatin 70 mg/m2 on day 1 by intravenous infusion, administrated every 3 weeks for 2 to 6 cycles. All patients who received 2 or more cycles could be evaluated. Disease control rate （DCR） was the primary end point; secondary end points included progression-free survival （PFS）, 1-year survival rate and safety.Results：There was 1 case with complete response （CR）, 44 cases achieved partial response （PR）, 50 had stable disease （SD） and 26 cases had progressive disease （PD） in the overall cases. ORR and DCR were 37.2% （45/121） and 78.5% （95/121）, respectively. The median PFS time was 5.2 months and 1-year survival rate was 59.0%. In pemetrexed combined with carboplatin group, the ORR and DCRwere 38.3% （23/60） and 78.3% （47/60）, respectively; The median PFS was 5.1 months （95%CI： 3.8-6.4 month） and 1-year survival rate was 55.2%. The patients treated with pemetrexed plus cisplatin, the ORR and DCR were 36.1% （22/61） and 78.7% （48/61）, respectively. Median PFS was 6.2 months （95%CI： 4.3-8.1 month） and 1-year survival rate was 62.5%. There were no statistical differences between carboplatin/pemetrexed and cisplatin/pemetrexed for both ORR, DCR, PFS and 1-year survival rate （P〉0.05）. The major adverse effects were leukopenia, neutropenia, fatigue and gastrointestinal reaction.Conclusion：Pemetrexed plus platinum chemotherapy could be considered as the ifrst-line treatment option for advanced non-squamous NSCLC patients. Pemetrexed combined with carboplatin/ cisplatin regimen has efifcacy with mild toxicity and better tolerability.