Department of Radiation Oncology, Yonsei Cancer Center, Heavy Ion Therapy Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea; R&D Center, Hanlim Pharm. Co, Ltd, Seoul, Republic of Korea.
Int J Radiat Oncol Biol Phys. 2024 Oct 1;120(2):432-438. doi: 10.1016/j.ijrobp.2024.03.033. Epub 2024 Mar 31.
We aimed to investigate the safety and efficacy of HL301, a standardized combination product of 7 medicinal plants, in radiation pneumonitis in patients with unresectable non-small cell lung cancer undergoing curative concurrent chemoradiotherapy.
The target accrual was 87 and a total of 63 patients were enrolled due to poor accrual rate. We randomly assigned the 63 patients to receive a placebo (arm A), or 1200 mg HL301 (arm B), or 1800 mg HL301 (arm C). Patients received weekly paclitaxel and carboplatin concurrently with intensity-modulated radiation therapy at 60 to 66 Gy in conventional fractionation. Durvalumab was administered as a maintenance treatment according to standard clinical practice. HL301 was administered orally, daily for 12 weeks. The primary endpoint was incidence of grade ≥2 radiation pneumonitis at 24 weeks postchemoradiotherapy.
The baseline characteristics of the patients were well balanced. The drug was tolerable with a compliance rate of 86.6%, 86.2%, and 88.8% in arms A, B, and C, respectively (P = .874). None of the patients experienced severe drug-related adverse events. No significant difference in the rate of adverse events were observed between the treatment arms. The incidence of grade ≥2 radiation pneumonitis at 24 weeks postchemoradiotherapy was 37.5% (95% CI, 18.5%-61.4%), 55.6% (95% CI, 33.7%-75.4%), and 52.4% (95% CI, 32.4%-71.7%) in arms A, B, and C, respectively (P = .535).
This is the first exploratory clinical trial to test the safety and efficacy of HL301 in patients with non-small cell lung cancer. Safety and feasibility of HL301 were established but no signals of efficacy in reducing radiation pneumonitis was observed in this dose level.
我们旨在研究 HL301（7 种药用植物标准化组合产品）在接受根治性同步放化疗的不可切除非小细胞肺癌患者中放射性肺炎的安全性和疗效。
目标入组人数为 87 人，但由于入组率低，共入组 63 人。我们将 63 名患者随机分配接受安慰剂（A 组）、1200mg HL301（B 组）或 1800mg HL301（C 组）。患者每周接受紫杉醇和顺铂联合常规分割强度调制放疗 60-66Gy。根据标准临床实践，使用度伐鲁单抗进行维持治疗。HL301 每日口服，持续 12 周。主要终点是放化疗后 24 周时≥2 级放射性肺炎的发生率。
患者的基线特征均衡良好。药物的耐受性良好，A、B 和 C 组的依从率分别为 86.6%、86.2%和 88.8%（P =.874）。没有患者出现严重的药物相关不良事件。治疗组之间未观察到不良反应发生率的显著差异。放化疗后 24 周时≥2 级放射性肺炎的发生率分别为 37.5%（95%CI，18.5%-61.4%）、55.6%（95%CI，33.7%-75.4%）和 52.4%（95%CI，32.4%-71.7%）在 A、B 和 C 组（P =.535）。
这是首次探索性临床试验，旨在测试 HL301 在非小细胞肺癌患者中的安全性和疗效。HL301 的安全性和可行性得到了确立，但在该剂量水平下，没有观察到降低放射性肺炎的疗效信号。
