Background and objective: Platinum-based chemotherapy doublets reached an efficacy plateau in nonsmall-cell lung cancer (NSCLC). This randomized controlled study prospectively assessed the efficacy and safety of cisplatin plus gemcitabine with either Sorafenib or placebo as first-line therapy for NSCLC.
Methods: Thirty patients, which were confirmed advanced NSCLC histologically or cytologically, were randomly assigned to receive up to six cycles of cisplatin plus gemcitabine with sorafenib or placebo. The maintenance of sorafenib or placebo after chemotherapy will continued in patients with response or stable disease until disease progression or unacceptable adverse events.
Results: Overall demographics were balanced between experimental group (sorafenib+chemotherapy) and controlled group (chemotherapy only). Overall response (OS) rate was 55.6% and 41.7% in experimental arm and controlled arm, respectively (P=0.905). Median progressive-free survival (PFS) and median overall survival were similar (5 months vs 4 months, P=0.75; 18 months vs 18 months, P=0.68). Adverse events were tolerable, though the risk of hypertension and diarrhea was increase in experimental arm. Since patients with ECOG PS 0, stage IIIb, no liver metastasis and tyrasine kinasis inhibitor treatment after study had longer survive, these factors seemed to be predictive factors favor of survival in Cox regression analyses.
Conclusions: No additional benefit of response rate, PFS or OS were observed from adding targeted agent-sorafenib to regular cisplatin plus gemcitabine chemotherapy. Selecting aproper patients is needed in further study.
背景与目的: 新药含铂两药联合治疗晚期非小细胞肺癌（non-small cell lung cancer, NSCLC）的疗效已达到平台期，本研究采用前瞻性随机对照的方法比较了吉西他滨顺铂联合索拉非尼或安慰剂一线治疗晚期NSCLC的疗效和安全性。
方法: 经细胞学或病理学证实的30例晚期NSCLC患者随机进行吉西他滨顺铂联合索拉非尼或安慰剂治疗，化疗不超过6个周期，有效或稳定的患者继续服用索拉非尼或安慰剂，直至疾病进展或不能耐受不良反应。
结果: 实验组（索拉非尼联合化疗组）和对照组（单纯化疗组）的分布基本平衡，两组有效率（response rate, RR）分别为55.6%和41.7%（P=0.905）；两组的中位无疾病进展时间（progress-free survival, PFS）相似，分别为5个月和4个月（P=0.75）；两组的中位生存时间（overall survival, OS）均为18个月，无统计学差异（P=0.68）。不良反应可耐受，实验组的高血压和腹泻发生率较对照组高。Cox多因素回归分析显示，身体状况好（ECOG评分为0分）、肺癌分期早（Ⅲb期）、无肝转移和后续进行酪氨酸激酶抑制剂（tyrasine kinasis inhibitor, TKI）治疗的患者生存明显延长，提示这些因素为良好的预后因素。
结论: 在常规吉西他滨顺铂化疗的基础上增加靶向药物索拉非尼并未增加RR、PFS以及OS，后续类似研究需谨慎选择合适的患者。