Tetsuji Takayama, Koichi Okamoto, Hideki Ishikawa, Kaizo Kagemoto, Tatsuhisa Yasaka, Takashi Hisabe, Koichi Kawabe, Toyotaka Kasai, Masaya Kubota, Masahito Shimizu, Tomoyuki Abe, Jiro Nakamoto, Masahiko Nakasono, Sho Takahashi, Keita Harada, Shinji Kitamura, Hisashi Nakamura, Shinya Minami, Manabu Sawatani, Koshi Fujikawa, Toshihito Tanahashi, Shin-Ichiro Hori, Tsutomu Nagata, Yasushi Sato, Michihiro Mutoh, J-CAP-C study group
Between April 1, 2016, and March 31, 2020, 577 patients were randomly assigned to curcumin (n=287) or placebo groups (n=290). The detection rate of recurrent colorectal adenomas at 2 years, the primary endpoint, did not differ significantly between groups (risk ratio [RR] 0.98; 95% CI 0.82-1.16). However, the detection rate of adenomas ≥6 mm, a prespecified lesion category recommended for endoscopic resection in Japanese guidelines, was significantly lower with curcumin (RR, 0.56; 95% CI, 0.33-0.95; P=0.04). The per-patient number of adenomas ≥6 mm was also significantly lower (P=0.03), and the median size of all detected adenomas was significantly smaller in the curcumin group (P=0.003). The inhibitory effect appeared more pronounced in patients with higher baseline adenoma burden and in men in exploratory analyses. Treatment-related adverse events were infrequent and mild.
INTRODUCTION: Experimental and limited clinical studies suggest that curcumin has chemopreventive activity in the colorectum. This large-scale clinical trial evaluated the efficacy and safety of curcumin in patients with previously endoscopically resected colorectal neoplasia.
METHODS: This randomized, double-blind, placebo-controlled multicenter trial enrolled patients with previously resected colorectal neoplasia. Eligible patients were randomly assigned (1:1), using a stratified, computer-generated scheme to receive oral submicron-powdered curcumin (Theracurmin®; 180 mg twice daily) or identical placebo capsules for 2 years. All analyses were performed according to a modified intention-to-treat principle including all randomly assigned patients who underwent the 2-year colonoscopy.
RESULTS: Between April 1, 2016, and March 31, 2020, 577 patients were randomly assigned to curcumin (n=287) or placebo groups (n=290). The detection rate of recurrent colorectal adenomas at 2 years, the primary endpoint, did not differ significantly between groups (risk ratio [RR] 0.98; 95% CI 0.82-1.16). However, the detection rate of adenomas ≥6 mm, a prespecified lesion category recommended for endoscopic resection in Japanese guidelines, was significantly lower with curcumin (RR, 0.56; 95% CI, 0.33-0.95; P=0.04). The per-patient number of adenomas ≥6 mm was also significantly lower (P=0.03), and the median size of all detected adenomas was significantly smaller in the curcumin group (P=0.003). The inhibitory effect appeared more pronounced in patients with higher baseline adenoma burden and in men in exploratory analyses. Treatment-related adverse events were infrequent and mild.
DISCUSSION: Curcumin inhibited the growth of recurrent colorectal adenomas, despite no significant reduction in the overall incidence of recurrence. This is the first large-scale randomized clinical trial demonstrating the suppressive efficacy of curcumin against colorectal neoplasia, and also highlighting the importance of incorporating growth-related endpoints, in addition to incidence- or detection-based endpoints, in chemoprevention studies. (jRCTs061180079).