Katahara Honami, Baba Kaede, Nakajima Hiromichi, Funasaka Chikako, Kondoh Chihiro, Naito Yoichi, Udagawa Hibiki, Shitara Kohei, Sasaki Tomoaki, Kawasaki Toshikatsu, Mukohara Toru
Department of Pharmacy, National Cancer Center Hospital East, Kashiwa, Japan.
Department of Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Front Oncol. 2025 May 16;15:1567317. doi: 10.3389/fonc.2025.1567317. eCollection 2025.
Drug-induced interstitial lung disease (DIILD) is a serious complication of cancer treatment that is primarily treated with corticosteroids. However, effective standardized regimens for corticosteroid-refractory DIILD have not been established. Cyclophosphamide (CPA) is an immunosuppressant that is potentially effective against DIILD, but supporting evidence is limited, particularly for diseases induced by novel chemotherapeutic drugs. In this study, we examined the efficacy and safety of CPA in corticosteroid-refractory DIILD caused by various anticancer drugs.
We retrospectively reviewed the medical records of patients who underwent CPA therapy for corticosteroid-refractory DIILD at the National Cancer Center Hospital East between January 2013 and October 2023. Corticosteroid-refractory DIILD was defined as cases of DIILD classified as grade ≥3 according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, in which no improvement was observed within 48 hours after initiating corticosteroid therapy. The primary endpoint was 30-day survival post-CPA. The secondary endpoints included radiological improvements and changes in oxygen supplementation.
Fifteen patients (median age 73 years; 80% male) were included in the analysis. Patients were classified into molecular-targeted drugs (MT; 20%, 3/15), MT + cytotoxic drugs (33%, 5/15), immune checkpoint inhibitors (ICI) ± cytotoxic drugs (27%, 4/15), and cytotoxic drugs alone (20%, 3/15) groups. The overall 30-day survival rate was 47% (7/15). Improvement of oxygen demand allowed 20% (3/15) of patients to discontinue oxygen supplementation. CPA demonstrated drug class-dependent efficacy: highest in the MT group (67% survival, 2/3), less benefit in the cytotoxic drugs alone group (0% survival, 0/3). Adverse events included grade 3 anemia (n=2), grade 4 neutropenia (n=1), and grade 2 cytomegalovirus infection (n=1), with no treatment-related deaths.
CPA exhibited potential efficacy for corticosteroid-refractory DIILD, particularly in patients with MT-induced DIILD, with manageable toxicity. The differential responses based on drug category suggest tailored approaches to DIILD management may be warranted. These findings may contribute to optimizing the management of severe DIILD during cancer treatment.
药物性间质性肺病（DIILD）是癌症治疗的一种严重并发症，主要采用皮质类固醇进行治疗。然而，针对皮质类固醇难治性DIILD的有效标准化治疗方案尚未确立。环磷酰胺（CPA）是一种免疫抑制剂，对DIILD可能有效，但支持证据有限，尤其是对于新型化疗药物所致的疾病。在本研究中，我们考察了CPA治疗由各种抗癌药物引起的皮质类固醇难治性DIILD的疗效和安全性。
我们回顾性分析了2013年1月至2023年10月在国立癌症中心东医院接受CPA治疗皮质类固醇难治性DIILD患者的病历。皮质类固醇难治性DIILD定义为根据不良事件通用术语标准（CTCAE）第5.0版分类为≥3级的DIILD病例，在开始皮质类固醇治疗后48小时内未观察到改善。主要终点是CPA治疗后30天生存率。次要终点包括影像学改善和氧疗变化。
15例患者（中位年龄73岁；80%为男性）纳入分析。患者分为分子靶向药物（MT；20%，3/15）、MT + 细胞毒性药物（33%，5/15）、免疫检查点抑制剂（ICI）± 细胞毒性药物（27%，4/15）和单纯细胞毒性药物（20%，3/15）组。总体30天生存率为47%（7/15）。氧需求的改善使20%（3/15）的患者停止吸氧。CPA显示出药物类别依赖性疗效：在MT组中最高（生存率67%，2/3），在单纯细胞毒性药物组中获益较少（生存率0%，0/3）不良事件包括3级贫血（n = 2）、4级中性粒细胞减少（n = 1）和2级巨细胞病毒感染（n = 1），无治疗相关死亡。
CPA对皮质类固醇难治性DIILD显示出潜在疗效，尤其是在MT诱导的DIILD患者中，且毒性可控。基于药物类别的不同反应提示，可能需要针对DIILD管理采取个性化方法。这些发现可能有助于优化癌症治疗期间严重DIILD的管理。
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