한빛사논문
- 조회956
Hyung-Joo Oh1#, Suk-Chul Bae2#, In-Jae Oh1, Cheol-Kyu Park1, Kyoung-Mi Jung2, Da-Mi Kim2, Jung-Won Lee2, Chang Kyun Kang3, Il Yeong Park3, and Young-Chul Kim1*
1Department of Internal Medicine, Chonnam National University Medical School, and CNU Hwasun Hospital, Hwasun, Jeonnam, South Korea.
2Department of Biochemistry, College of Medicine, Chungbuk National University, Cheongju, South Korea.
3College of Pharmacy, Chungbuk National University, Cheongju, South Korea.
#H.-J. Oh and S.-C. Bae contributed equally as co-first authors of this article.
*Corresponding Author: Young-Chul Kim
Abstract
Purpose: RUNX3 is a tumor suppressor gene, which is inactivated in approximately 70% of lung adenocarcinomas. Nicotinamide, a sirtuin inhibitor, has demonstrated potential in re-activating epigenetically silenced RUNX3 in cancer cells. This study assessed the therapeutic benefits of combining nicotinamide with first-generation EGFR-tyrosine kinase inhibitors (TKI) for patients with stage IV lung cancer carrying EGFR mutations.
Patients and methods: We assessed the impact of nicotinamide on carcinogen-induced lung adenocarcinomas in mice and observed that nicotinamide increased RUNX3 levels and inhibited lung cancer growth. Subsequently, 110 consecutive patients with stage IV lung cancer who had EGFR mutations were recruited: 70 females (63.6%) and 84 never-smokers (76.4%). The patients were randomly assigned to receive either nicotinamide (1 g/day, n = 55) or placebo (n = 55). The primary and secondary endpoints were progression-free survival (PFS) and overall survival (OS), respectively.
Results: After a median follow-up of 54.3 months, the nicotinamide group exhibited a median PFS of 12.7 months [95% confidence interval (CI), 10.4-18.3], while the placebo group had a PFS of 10.9 months (9.0-13.2; P = 0.2). The median OS was similar in the two groups (31.0 months with nicotinamide vs. 29.4 months with placebo; P = 0.2). Notably, subgroup analyses revealed a significant reduction in mortality risk for females (P = 0.01) and never-smokers (P = 0.03) treated with nicotinamide.
Conclusions: The addition of nicotinamide with EGFR-TKIs demonstrated potential improvements in PFS and OS, with notable survival benefits for female patients and those who had never smoked (ClinicalTrials.gov Identifier: NCT02416739).
논문정보
- Research article
- 2024년 04월 (BRIC 등록일 2024-04-12)
- 국내 연구진
- 의약학 > 종양의학
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