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Supplementary Material for: 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

posted on 18.11.2022, 12:59 authored by Kawamura K., Matsushima H., Sakai H., Iwashima A., Nakamura S., Kojima T., Sasaki S., Shigenaga T., Natsume I., Sasaki T., Ohsaki Y., Iwanaga K., Nishi K., Mitsuishi Y., Taniguchi H., Sato K., Yamauchi M., Nakajima M., Takahashi K.
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.