Prospective observational study of the efficacy of oral uracil and tegafur plus leucovorin for stage II colon cancer with risk factors for recurrence using propensity score matching (JFMC46-1201)

BMC Cancer

Satoshi Morita¹  Kazuhiro Sakamoto²  Masataka Taguri³  Takao Takahashi⁴  Masataka Ikeda⁵  Hideo Baba⁶  Kiyoshi Maeda⁷  Ichinosuke Hyodo⁸  Hiroki Ohge⁹  Mitsuo Kusano^1,10  Michio Itabashi^1,11  Yutaka Ogata^1,12  Ken Kondo^1,13  Hiroyuki Masuko^1,14  Takashi Tsuchiya^1,15  Sotaro Sadahiro^1,16  Toshihiko Sato^1,17  Madoka Hamada^1,18  Junichi Sakamoto^1,19  Keiichi Takahashi^2,20 

[1] Department of Biomedical Statistics and Bioinformatics, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, 606-8507, Kyoto, Japan;Department of Coloproctological Surgery, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, 113-8421, Tokyo, Japan;Department of Data Science, Yokohama City University, 22-2 Seto, Kanazawa-ku, 236-0027, Yokohama, Kanagawa, Japan;Department of Digestive Surgery, Gifu University Hospital, 1-1 Yanagido, 501-1194, Gifu, Japan;Department of Gastroenterological Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, 663-8501, Nishinomiya, Hyogo, Japan;Department of Gastroenterological Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, 860-8556, Kumamoto, Japan;Department of Gastroenterological Surgery, Osaka City General Hospital, 2-13-22 Miyakojimahondori, Miyakojima-ku, 534-0021, Osaka, Japan;Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, 160 Kou, Minamiumemoto, 791-0280, Matsuyama, Ehime, Japan;Department of Infectious Diseases, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, 734-8551, Hiroshima, Japan;Department of Physical Medicine, Yoichi Hospital, 19-1-1 Kurokawa-cho Yoichi, 046-0003, Hokkaido, Japan;Department of Surgery, Division of Inflammatory Bowel Disease Surgery, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, 162-8666, Tokyo, Japan;Department of Surgery, Kurume University Hospital Cancer Center, 67 Asahi-machi, 830-0011, Kurume, Fukuoka, Japan;Department of Surgery, Nagoya Medical Center, 4-1-1 Sannomaru, Naka-ku, 460-0001, Nagoya, Aichi, Japan;Department of Surgery, Nikko Memorial Hospital, 1-5-13 Shintomi-cho, 051-8501, Muroran, Hokkaido, Japan;Department of Surgery, Sendai City Medical Center, 5-22-1 Tsurugaya, Miyagino-ku, Sendai, 983-0824, Miyagi, Japan;Department of Surgery, Tokai University, 143 Shimokasuya, 259-1193, Isehara, Kanagawa, Japan;Department of Surgery, Yamagata Prefectural Central Hospital, 1800 Aoyagi, 990-2292, Yamagata, Japan;Division of Gastrointestinal Surgery, Kansai Medical University Hospital, 2-3-1 Shinmachi Hirakata, 573-1191, Osaka, Japan;Tokai Central Hospital, 4-6-2 Sohara Higashijima-cho, 504-8601, Kakamigahara, Gifu, Japan;Tokyo Metropolitan Health and Hospitals Corporation Ohkubo Hospital, 2-44-1 Kabuki-cho, Shinjuku-ku, 160-8488, Tokyo, Japan;

关键词: Adjuvant chemotherapy;    Colon cancer;    High-risk;    Stage II;    Propensity score;    Risk factor;    Tegafur;    Uracil;    Leucovorin;    Inverse probability of treatment weighting;   

DOI  :  10.1186/s12885-022-09267-z

来源: Springer

【 摘 要 】

BackgroundThe efficacy of adjuvant chemotherapy for high-risk stage II colon cancer (CC) has not been well established. We compared the effects of surgery with and without oral uracil and tegafur plus leucovorin (UFT/LV) in patients with high-risk stage II CC, adjusting for potential risk factors.MethodsWe enrolled patients with histologically confirmed stage II colon adenocarcinoma with at least one of the following conditions: T4 disease, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, or < 12 dissected lymph nodes. Patients chose to be non-randomized or randomized to undergo surgery alone (NR-Group S or R-Group S) or surgery followed by 6 months of UFT/LV (NR-Group U or R-Group U). The primary endpoint was disease-free survival (DFS) after adjusting for previously reported risk factors using propensity score matching (1:2) and inverse probability of treatment weighting (IPTW) in the non-randomized arm.ResultsOverall, 1,902 (98%) and 36 (2%) patients were enrolled in the non-randomized and randomized arms, respectively. There were too few patients in the randomized arm and these were therefore excluded from the analysis. Of the 1,902 patients, 402 in NR-Group S and 804 in NR-Group U were propensity score-matched. The 3-year DFS rate (95% confidence interval) was significantly higher in NR-Group U (80.9% [77.9%–83.4%]) than in NR-Group S (74.0% [69.3%–78.0%]) (hazard ratio, 0.64 [0.50–0.83]; P = 0.0006). The 3-year overall survival rate was not significantly different between NR-Group S and NR-Group U. Significantly higher 3-year DFS (P = 0.0013) and overall survival (P = 0.0315) rates were observed in NR-Group U compared with NR-Group S using IPTW.ConclusionsAdjuvant chemotherapy with UFT/LV showed a significant survival benefit over surgery alone in patients with high-risk stage II CC characterized by at least one of the following conditions: T4 disease, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, or < 12 dissected lymph nodes.Trial registrationJapan Registry of Clinical Trials: jRCTs031180155 (date of registration: 25/02/2019) (UMIN Clinical Trials Registry: UMIN000007783, date of registration: 18/04/2012).

【 授权许可】

CC BY