Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho Sunto-gun, Japan.
Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
J Clin Oncol. 2020 Dec 20;38(36):4292-4301. doi: 10.1200/JCO.20.01806. Epub 2020 Nov 2.
To verify the superiority of irinotecan plus cisplatin over etoposide plus cisplatin as postoperative adjuvant chemotherapy for patients with pathologic stage I-IIIA, completely resected, high-grade neuroendocrine carcinoma (HGNEC) of the lung.
This was a randomized, open-label, phase III study on patients with completely resected stage I-IIIA HGNEC of the lung. They were randomly assigned to receive either etoposide (100 mg/m, days 1-3) plus cisplatin (80 mg/m, day 1) or irinotecan (60 mg/m, days 1, 8, 15) plus cisplatin (60 mg/m, day 1) up to four cycles. The primary end point was relapse-free survival (RFS) in the intention-to-treat population. This trial was registered with the Japan Registry of Clinical Trials (jRCTs031180216).
Between April 2013 and October 2018, 221 patients were enrolled (etoposide plus cisplatin arm, 111 patients; irinotecan plus cisplatin arm, 110 patients). In the second interim analysis, early termination of the trial was recommended because of futility. At a median follow-up of 24.1 months, the 3-year RFS was 65.4% for etoposide plus cisplatin and 69.0% for irinotecan plus cisplatin, with a hazard ratio of 1.076 (95% CI, 0.666 to 1.738; one-sided log-rank = .619). Grade 3-4 adverse events were more frequent in the etoposide plus cisplatin arm, with febrile neutropenia (20% of 109 patients 4% of 107 patients) and neutropenia (97% 36%) being the most common. Meanwhile, grade 3-4 anorexia (6% 11%) and diarrhea (1% 8%) were more frequently observed in the irinotecan plus cisplatin arm.
Irinotecan plus cisplatin is not superior to etoposide plus cisplatin for improving RFS in patients with completely resected HGNEC; thus, etoposide plus cisplatin remains the standard treatment.
验证伊立替康联合顺铂对比依托泊苷联合顺铂作为完全切除、病理分期为Ⅰ-Ⅲ A 期的高级别神经内分泌肺癌患者术后辅助化疗的优势。
这是一项针对完全切除的Ⅰ-Ⅲ A 期高级别神经内分泌肺癌患者的随机、开放标签、Ⅲ 期研究。患者被随机分配接受依托泊苷（100 mg/m²，第 1-3 天）联合顺铂（80 mg/m²，第 1 天）或伊立替康（60 mg/m²，第 1、8、15 天）联合顺铂（60 mg/m²，第 1 天），最多四个周期。主要终点是意向治疗人群的无复发生存率（RFS）。该试验在日本临床试验注册中心（jRCTs031180216）注册。
2013 年 4 月至 2018 年 10 月期间，共纳入 221 例患者（依托泊苷联合顺铂组 111 例，伊立替康联合顺铂组 110 例）。在第二次中期分析中，由于无效建议提前终止试验。中位随访 24.1 个月时，依托泊苷联合顺铂组的 3 年 RFS 为 65.4%，伊立替康联合顺铂组为 69.0%，风险比为 1.076（95%CI，0.666 至 1.738；单侧对数秩检验=0.619）。依托泊苷联合顺铂组更常见 3-4 级不良事件，发热性中性粒细胞减少症（109 例患者中有 20%，107 例患者中有 4%）和中性粒细胞减少症（97%，36%）最常见。而伊立替康联合顺铂组更常发生 3-4 级厌食症（6%，11%）和腹泻（1%，8%）。
伊立替康联合顺铂并未改善完全切除的高级别神经内分泌肺癌患者的 RFS，因此依托泊苷联合顺铂仍是标准治疗。
