一项 5-氨基乙酰丙酸盐酸盐和柠檬酸亚铁钠预防肺癌顺铂为基础的化疗引起肾毒性的随机 2 期研究。
A Randomized Phase 2 Study of 5-Aminolevulinic Acid Hydrochloride and Sodium Ferrous Citrate for the Prevention of Nephrotoxicity Induced by Cisplatin-Based Chemotherapy of Lung Cancer.
机构信息
Department of Respiratory Medicine, Saiseikai Kumamoto Hospital, Kumamoto, Japan.
Department of Respiratory Medicine, Saitama Red Cross Hospital, Saitama, Japan.
出版信息
Oncology. 2022;100(11):620-632. doi: 10.1159/000526977. Epub 2022 Sep 13.
INTRODUCTION
Cisplatin-based chemotherapy was established in the 1980s, and it has been improved by the development of a short hydration protocol in lung cancer therapy. However, cisplatin-based chemotherapy is still associated with renal toxicity. Because 5-aminolevulinic acid (5-ALA) with sodium ferrous citrate (SFC) is known to be a mitochondrial activator and a heme oxygenase-1 (HO-1) inducer, 5-ALA with SFC is speculated to mitigate cisplatin-induced renal inflammation.
METHODS
We investigated the effects of oral administration of 5-ALA with SFC for preventing cisplatin-based nephrotoxicity in patients with lung cancer and evaluated its benefits for patients who received cisplatin-based chemotherapy. The primary endpoint was the significance of the difference between the serum creatinine (sCr) levels of the patients administered 5-ALA with SFC and those given placebo after course 1 of chemotherapy. The difference in the estimated glomerular filtration rate (eGFR) between the two groups was also evaluated as the secondary endpoint.
RESULTS
The double-blind, randomized two-arm studies were conducted at 15 medical facilities in Japan; 54 male and 20 female patients with lung cancer who received cisplatin-based chemotherapy between the ages of 42 and 75 years were included in the study. The compliance rate was greater than 94% in the primary assessment and subsequent drug administration periods. All enrolled patients completed the four cycles of cisplatin-based chemotherapy with short hydration. The average level of sCr on day 22 of course 1 was 0.707 mg/dL in the group treated with 5-ALA and SFC and 0.735 mg/dL in the placebo group, respectively, and the sCr in the test group was significantly lower than that in the placebo group (p = 0.038). In addition, the eGFR was significantly higher in the SPP-003 group than in the placebo group up to day 1 of course 3 (84.66 and 75.68 mL/min/1.73 m2, respectively, p = 0.02) and kept better even after the last administration of the study drug (82.37 and 73.49 mL/min/1.73 m2, respectively, p = 0.013).
CONCLUSIONS
The oral administration of 5-ALA with SFC is beneficial to patients undergoing cisplatin-based chemotherapy for lung cancer with short hydration.
简介
顺铂为基础的化疗在 20 世纪 80 年代确立，在肺癌治疗中通过发展短期水化方案得到了改进。然而，顺铂为基础的化疗仍与肾毒性相关。因为 5-氨基酮戊酸（5-ALA）联合柠檬酸亚铁（SFC）已知是线粒体激活剂和血红素加氧酶-1（HO-1）诱导剂，所以推测 5-ALA 联合 SFC 可以减轻顺铂引起的肾炎症。
方法
我们研究了口服 5-ALA 联合 SFC 对预防肺癌患者顺铂肾毒性的效果，并评估了其对接受顺铂为基础化疗的患者的益处。主要终点是化疗第 1 疗程后，接受 5-ALA 联合 SFC 治疗的患者与接受安慰剂治疗的患者之间血清肌酐（sCr）水平的差异的显著性。两组间估算肾小球滤过率（eGFR）的差异也作为次要终点进行评估。
结果
这项双盲、随机两臂研究在日本的 15 家医疗机构进行；纳入了年龄在 42 至 75 岁之间接受顺铂为基础化疗的 54 名男性和 20 名女性肺癌患者。主要评估和后续药物给药期间的依从率均大于 94%。所有入组患者均完成了四周期的顺铂为基础短水化化疗。第 1 疗程第 22 天，5-ALA 联合 SFC 组 sCr 平均水平为 0.707mg/dL，安慰剂组为 0.735mg/dL，试验组 sCr 明显低于安慰剂组（p=0.038）。此外，直到第 3 疗程第 1 天，SPP-003 组的 eGFR 明显高于安慰剂组（分别为 84.66 和 75.68mL/min/1.73m2，p=0.02），甚至在最后一次研究药物给药后仍保持更好（分别为 82.37 和 73.49mL/min/1.73m2，p=0.013）。
结论
口服 5-ALA 联合 SFC 对接受短水化顺铂为基础化疗的肺癌患者有益。
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