Sarah Cannon Research Institute, Nashville, TN 37203, USA.
Lung Cancer. 2012 Oct;78(1):70-5. doi: 10.1016/j.lungcan.2012.06.008. Epub 2012 Sep 1.
Epothilones, a new class of cytotoxic agents, have demonstrated activity in non-small-cell lung cancer (NSCLC). This phase II study examined ixabepilone/carboplatin (cohort A) and ixabepilone/carboplatin/bevacizumab (cohort B) as first-line therapy for patients with advanced NSCLC.
Patients were enrolled to either cohort A or B at physician discretion and when eligibility met. Eligible patients had newly diagnosed stage III/IV NSCLC, ECOG PS 0-1, adequate organ function, no active CNS metastases, and, in cohort B, bevacizumab treatment criteria. Both cohorts received ixabepilone 30 mg/m2 and carboplatin AUC=6 IV day 1 every 3-weeks for a maximum of 6 cycles. Patients assigned to cohort B also received bevacizumab 15 mg/kg IV day 1 of each cycle, and could continue single-agent bevacizumab for 6 additional cycles.
Eighty-two patients (median age, 63 years; majority stage IV and former smokers) were enrolled from 11/08 to 10/09 (A-42, B-40) and received medians of 4 and 6 cycles, respectively. The ORRs were 29% and 50%. After median follow up of 17.5 months (A) and 15.7 months (B), median progression free survivals were A-5.3 months (95% CI 2.8-8.6) and B-6.7 months (95% CI 5.1-8.4), with median overall survivals of 9.3 months (95% CI 6.4-16.6) 13.2 months (95% CI 8.9-upper limit not reached), respectively. Grade 3/4 toxicity included: anemia (A-10%, B-27%), neutropenia (A-31%, B-48%), thrombocytopenia (A-19%, B-20%), fatigue (A-10%, B-23%), infection (A-5%, B-20%), and hypersensitivity reaction (A-2%, B-5%). There was one treatment-related death, due to hemoptysis in a cohort B patient with squamous histology.
Ixabepilone can be safely combined with carboplatin in newly diagnosed patients with advanced NSCLC. The benefits of treatment appear consistent with those achieved with other modern platinum-doublet regimens. The addition of bevacizumab increases toxicities, however, these are largely expected and reversible. The high ORR and OS observed in the bevacizumab-cohort are encouraging, but would require validation in a larger randomized trial of cohort A versus B.
埃坡霉素是一类新型细胞毒药物，在非小细胞肺癌（NSCLC）中具有活性。这项 II 期研究评估了伊沙匹隆/卡铂（队列 A）和伊沙匹隆/卡铂/贝伐珠单抗（队列 B）作为晚期 NSCLC 患者的一线治疗。
根据医生的判断和符合入组条件，患者被分配至队列 A 或 B。入组患者为初诊 III/IV 期 NSCLC，ECOG PS 0-1，器官功能良好，无活动性 CNS 转移，且在队列 B 中符合贝伐珠单抗治疗标准。两个队列均接受伊沙匹隆 30mg/m2 和卡铂 AUC=6 IV 第 1 天，每 3 周一次，最多 6 个周期。分配至队列 B 的患者还接受贝伐珠单抗 15mg/kg IV 第 1 天，每个周期，并且可以继续接受单药贝伐珠单抗 6 个周期。
2008 年 11 月至 2009 年 10 月期间，共招募了 82 例患者（中位年龄 63 岁，多数为 IV 期和曾吸烟者），分别入组至队列 A（42 例）和队列 B（40 例），并分别接受了中位数为 4 个和 6 个周期的治疗。ORR 分别为 29%和 50%。中位随访 17.5 个月（A）和 15.7 个月（B）后，无进展生存期分别为 A-5.3 个月（95%CI 2.8-8.6）和 B-6.7 个月（95%CI 5.1-8.4），总生存期分别为 A-9.3 个月（95%CI 6.4-16.6）和 B-13.2 个月（95%CI 8.9-未达到上限）。3/4 级毒性包括：贫血（A-10%，B-27%）、中性粒细胞减少（A-31%，B-48%）、血小板减少（A-19%，B-20%）、疲劳（A-10%，B-23%）、感染（A-5%，B-20%）和过敏反应（A-2%，B-5%）。有 1 例与治疗相关的死亡，为队列 B 中一名鳞状组织学患者的咯血。
伊沙匹隆联合卡铂可安全用于初诊的晚期 NSCLC 患者。治疗的益处似乎与其他现代铂类双联方案一致。贝伐珠单抗的加入增加了毒性，但这些毒性在很大程度上是可预期的且是可逆的。在贝伐珠单抗组中观察到的高 ORR 和 OS 令人鼓舞，但需要更大规模的随机队列 A 与 B 试验来验证。
Zotero 插件