Lessons learned: The combination of bevacizumab with docetaxel-gemcitabine resulted in unacceptable toxicity, particularly a high rate of pulmonary toxicity (30%).Despite promising efficacy, excessive toxicity of this regimen does not support its use in patients with advanced nonsquamous non-small cell lung cancer.
Background: Prior to immunotherapy, standard treatment for advanced non-small cell lung cancer (NSCLC) was platinum doublet chemotherapy. In a previous phase II study, docetaxel-gemcitabine demonstrated comparable efficacy and tolerability to platinum doublets. In this phase II trial, we evaluated the efficacy and tolerability of adding bevacizumab to docetaxel- gemcitabine in patients with advanced nonsquamous NSCLC.
Methods: Patients with untreated advanced nonsquamous NSCLC were treated with up to six cycles of docetaxel-gemcitabine-bevacizumab, followed by bevacizumab until progression. The primary endpoint for this study was 1-year progression-free survival (PFS); secondary endpoints were safety, overall response rate (ORR) and overall survival (OS). The planned sample size was 46 patients.
Results: A total of 13 patients were enrolled and received a median of six cycles of chemotherapy and four cycles of bevacizumab. The treatment was poorly tolerated, with five patients requiring dose reduction and four discontinuing treatment for toxicity. Grade 3-5 nonhematologic toxicity was seen in 10 patients, and 4 (30%) were hospitalized with pulmonary toxicity possibly related to study drugs. At this point, enrollment was halted for safety concerns. The 12-month PFS was 8%. In 11 evaluable patients, ORR was 72%, median PFS 6 months, and median OS was 11 months.
Conclusion: Docetaxel, gemcitabine, and bevacizumab at this dose and schedule resulted in excessive toxicity. Despite promising efficacy, in light of efficacious and safe alternative therapies, this regimen should not be used to treat advanced NSCLC.
经验获取
• 贝伐单抗和多西他赛‐吉西他滨联合治疗可以产生不可接受的毒性，特别是肺毒性率较高 (30%)。
• 尽管疗效颇具前景，但是，由于此方案可以产生过多的毒性，因而不支持将其用于治疗晚期非鳞状非小细胞肺癌患者。
摘要
背景。在免疫治疗之前，晚期非小细胞肺癌 (NSCLC) 的标准治疗为含铂双药化疗。在既往的 II 期研究中，多西他赛‐吉西他滨治疗显示出可与含铂双药治疗相媲美的有效性和耐受性。在本次 II 期试验中，我们评估了在多西他赛‐吉西他滨治疗中添加贝伐单抗用于治疗晚期非鳞状 NSCLC 患者的有效性和耐受性。
方法。未经治疗的晚期非鳞状 NSCLC 患者接受长达 6 个周期的多西他赛‐吉西他滨‐贝伐单抗治疗，随后接受贝伐单抗治疗直至出现疾病进展。本研究的主要终点为 1 年无进展生存期 (PFS)；次要终点为安全性、总体反应率 (ORR) 和总生存期 (OS)。计划的样本量为 46 名患者。
结果。一共有 13 名患者入组并接受平均 6 个周期的化疗以及 4 个周期的贝伐单抗治疗。治疗的耐受性不佳，由于出现毒性，5 名患者需要减少剂量，4 名患者中断治疗。10 名患者出现 3–5 级非血液毒性，4 名患者 (30%) 因出现可能与研究药物相关的肺毒性而住院治疗。此时，因安全问题而停止招募。12 个月 PFS 为 8%。在 11 名可评估的患者中，ORR 为 72%，中位 PFS 为 6 个月，中位 OS 为 11 个月。
结论。按照此剂量和时间表实施的多西他赛、吉西他滨和贝伐单抗治疗会产生过多的毒性。尽管疗效颇具前景，但是，鉴于存在有效且安全的替代疗法，此方案不应被用于治疗晚期 NSCLC。
Trial registration: ClinicalTrials.gov NCT00970684.
© AlphaMed Press; the data published online to support this summary are the property of the authors.