TORG1835/NEXT-SHIP研究的原理与方案设计：一项关于卡铂、依托泊苷和尼达尼布用于伴有特发性肺纤维化的不可切除的局限期/广泛期小细胞肺癌的II期研究。
Rationale and protocol design for the TORG1835/NEXT-SHIP study: a phase II study of carboplatin, etoposide and nintedanib for unresectable limited/extensive disease small cell lung cancer with idiopathic pulmonary fibrosis.
作者信息
Ikeda Satoshi, Ogura Takashi, Kato Terufumi, Kenmotsu Hirotsugu, Iwasawa Tae, Misumi Toshihiro, Yamanaka Takeharu, Okamoto Hiroaki
机构信息
Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, 6-16-1 Tomioka-higashi, Kanazawa-ku, Yokohama-city, Kanagawa Prefecture, 236-0051, Japan.
Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama-city, Kanagawa Prefecture, Japan.
出版信息
Ther Adv Med Oncol. 2020 May 18;12:1758835920923431. doi: 10.1177/1758835920923431. eCollection 2020.
BACKGROUND
Interstitial pneumonia (IP) is one of the most common and poor prognostic comorbidities in patients with small cell lung cancer (SCLC). The pharmacotherapy for SCLC occasionally induces fatal acute exacerbation of comorbid IP, especially in patients with idiopathic pulmonary fibrosis (IPF). Safe and effective pharmacotherapy is of greater importance in patients with SCLC and IPF, because SCLC presents a poor prognosis without systemic treatment. Nintedanib is expected to restrain acute exacerbation and present angiogenesis-inhibiting effects.
METHODS
The TORG1835/NEXT-SHIP study is the world's first multi-center, single-arm, phase II trial for unresectable limited or extensive disease SCLC with IPF. The patients receive carboplatin (area under the curve 5, day 1), etoposide (<75 years old: 100 mg/m; ⩾75 years old: 80 mg/m; days 1-3), and nintedanib (150 mg twice a day) every 3 weeks for four cycles. After completion or discontinuation of carboplatin plus etoposide, the patients continue nintedanib until the discontinuation criteria are met. The primary endpoint is the incidence of acute exacerbation of IPF at 28 days after last administration of cytotoxic anti-cancer agents. We set an expected value of 5% and a threshold value of 20%. Taking statistical points (a/b errors: 0.05/0.75) and ineligible patients into account, the sample size was set at 33. The key secondary endpoints are time to first acute exacerbation of IPF, overall response rate, progression-free survival, overall survival, and toxicities.
DISCUSSION
Because there is no clinical trial for unresectable SCLC with IPF, our study would provide a major impact on clinical practice.
TRIAL REGISTRATION
Japan Registry of Clinical Trials, jRCTs031190119, registered date: October 18, 2019 - Retrospectively registered, https://jrct.niph.go.jp/en-latest-detail/jRCTs031190119.
背景
间质性肺炎（IP）是小细胞肺癌（SCLC）患者中最常见且预后较差的合并症之一。SCLC的药物治疗偶尔会引发合并的IP致命性急性加重，尤其是在特发性肺纤维化（IPF）患者中。安全有效的药物治疗对于SCLC和IPF患者更为重要，因为未经系统治疗的SCLC预后较差。尼达尼布有望抑制急性加重并呈现抗血管生成作用。
方法
TORG1835/NEXT-SHIP研究是世界上首个针对伴有IPF的不可切除局限性或广泛性疾病SCLC的多中心、单臂、II期试验。患者每3周接受一次卡铂（曲线下面积5，第1天）、依托泊苷（<75岁：100mg/m²；≥75岁：80mg/m²；第1 - 3天）和尼达尼布（150mg，每日两次），共四个周期。在完成或停用卡铂加依托泊苷后，患者继续服用尼达尼布直至符合停药标准。主要终点是末次给予细胞毒性抗癌药物后28天IPF急性加重的发生率。我们设定预期值为5%，阈值为20%。考虑到统计点（a/b错误：0.05/0.75）和不符合条件的患者，样本量设定为33。关键次要终点是IPF首次急性加重的时间、总缓解率、无进展生存期、总生存期和毒性。
讨论
由于尚无针对伴有IPF的不可切除SCLC的临床试验，我们的研究将对临床实践产生重大影响。
试验注册
日本临床试验注册中心，jRCTs031190119，注册日期：2019年10月18日 - 回顾性注册，https://jrct.niph.go.jp/en-latest-detail/jRCTs031190119 。
Zotero 插件