Leukotriene Receptor Antagonist Therapy for the Chemoprevention of Human Rectal Aberrant Crypt Foci: Nonrandomized, Open-Label, Controlled Trial.

Abstract

Leukotriene receptor antagonists (LTRA) are widely used drugs for treating allergic asthma, and they have recently been suggested to have a suppressive effect on carcinogenesis and cancer cell proliferation. Aberrant crypt foci (ACF) are considered a reliable surrogate biomarker of colorectal cancer. This prospective study explored the chemopreventive effect of an LTRA on colonic ACF formation and the safety of the medicine in patients as a pilot trial leading to a colorectal cancer chemoprevention trial.

This was a nonrandomized, open-label, controlled trial in patients with colorectal ACFs. The participants were allocated to LTRA or observation groups. Patients in the LTRA group received 10 mg of montelukast orally daily for 8 weeks. After the intervention, colonoscopy was performed to evaluate the changes in the number of ACFs.

From November 2017 to March 2020, 40 patients were enrolled. The first 30 were assigned to the LTRA group, and the remaining 10 were assigned to the observation group. In the LTRA group, the mean change in the number of ACFs per patient at 8 weeks from baseline was -2.4 ± 2.2, while the mean change in the observation group was 0.4 ± 2.3 (P = 0.002). There were no severe adverse events.

This is the first study to explore the effect of LTRAs against colorectal ACF formation in humans. LTRAs are potential candidates for chemoprevention in colorectal cancer.

PREVENTION RELEVANCE:

We conducted the first LTRA chemoprevention trial for human rectal ACFs, which is considered a surrogate marker of colorectal carcinogenesis. 8-week treatment with LTRA suppressed ACF formation and cell proliferation in colonic epithelium. LTRAs are possible candidates for chemoprevention in colorectal cancer. See related Spotlight, p. 637.

• Authors: Takuma Higurashi, Keiichi Ashikari, Shigeki Tamura, Yusuke Saigusa, Tomohiro Takatsu, Noboru Misawa, Tsutomu Yoshihara, Tetsuya Matsuura, Akiko Fuyuki, Hidenori Ohkubo, Takaomi Kessoku, Kunihiro Hosono, Masato Yoneda, Atsushi Nakajima
• Journal: Cancer prevention research (Philadelphia, Pa.) (Cancer Prev Res (Phila)) Vol. 15 Issue 10 Pg. 661-668 (10 04 2022) ISSN: 1940-6215 [Electronic] United States
• PMID: 36083855 (Publication Type: Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2022 American Association for Cancer Research.

Chemical References

• Leukotriene Antagonists

Topics

• Aberrant Crypt Foci (drug therapy, prevention & control)
• Carcinogenesis
• Chemoprevention
• Colorectal Neoplasms (drug therapy, prevention & control)
• Humans
• Leukotriene Antagonists (therapeutic use)
• Prospective Studies