International Journal of Clinical Oncology

, Volume 11, Issue 2, pp 133–139

Does a selective cyclooxygenase-2 inhibitor (tiracoxib) induce clinically sufficient suppression of adenomas in patients with familial adenomatous polyposis? A randomized double-blind placebo-controlled clinical trial

  • Takeo Iwama
  • Takayuki Akasu
  • Joji Utsunomiya
  • Tetsuichiro Muto



There have been few placebo-controlled randomized double-blind studies of the clinical effects of selective cyclooxygenase-2 (COX-2) inhibitors on the regression of colorectal tumors. This study was designed to examine the regressive effect of a selective COX-2 inhibitor, tiracoxib (JTE-522), on colorectal polyps in patients with familial adenomatous polyposis (FAP), and its safety.


Sixty-one patients with FAP diagnosed by Japanese criteria were assigned randomly to receive placebo or JTE-522, at either 150 mg or 200 mg, once daily orally for 26 weeks. Prior to and at the end of the medication period, endoscopy was performed. Adenomas located near an india-ink tattoo injected at the first colonoscopy were identified and measured. The response variables were the percent changes from the baseline in polyp numbers and in specified polyp diameters. Any adverse events that appeared in at least four persons were taken into consideration and compared between the JTE-522 treatment groups and the placebo group.


No change in polyp number (median, 0) was observed in any of the three groups. There were no differences between the placebo group and the two treatment groups in the change in polyp size. JTE-522 was well tolerated.


Our findings, in keeping with other reports on COX-2 inhibitors, indicated that the inhibition of a COX-2 with a moderate dose of a selective COX-2 inhibitor did not induce clinically sufficient regression of adenomas in patients with FAP in a limited (6-month) medication period.

Key words

Familial adenomatous polyposis Colorectal adenomas Cyclooxygenase-2 inhibitor Nonsteroidal anti-inflammatory drugs Chemoprevention of adenoma 


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  1. 1.
    Winawer, SJ, Zauber, AG, Ho, MN,  et al. 1993Prevention of colorectal cancer by colonoscopic polypectomyN Engl J Med32919771981CrossRefPubMedGoogle Scholar
  2. 2.
    Citarda, F, Tomaselli, G, Capocaccia, R,  et al. 2001Efficacy in standard clinical practice of colonoscopic polypectomy in reducing colorectal cancer incidenceGut48812815CrossRefPubMedGoogle Scholar
  3. 3.
    Powell, SM, Zilz, N, Beazer-Barclay, Y,  et al. 1992APC mutations occur early during colorectal tumorigenesisNature359235237CrossRefPubMedGoogle Scholar
  4. 4.
    Miyaki, M, Konishi, M, Kikuchi-Yanoshita, R,  et al. 1994Characteristic of somatic mutation of the adenomatous polyposis coli gene in colorectal tumorsCancer Res5430113020PubMedGoogle Scholar
  5. 5.
    Pollard, M, Luckert, PH 1980Indomethacin treatment of rats with dimethylhydrazine-induced intestinal tumorsCancer Treat Rep6413231327PubMedGoogle Scholar
  6. 6.
    Narisawa, T, Satoh, M, Sano, M,  et al. 1983Inhibition of initiation and promotion by N-methylnitrosourea-induced colon carcinogenesis in rats by non-steroid anti-inflammatory agent indomethacinCarcinogenesis412251227PubMedGoogle Scholar
  7. 7.
    Oshima, M, Dinchuk, JE, Kargman, SL,  et al. 1996Suppression of intestinal polyposis in ApcΔ716 knockout mice by inhibition of cyclooxygenase-2 (COX-2)Cell87803809CrossRefPubMedGoogle Scholar
  8. 8.
    Mahmoud, NN, Boolbol, SK, Dannenberg, AJ,  et al. 1998The sulfide metabolite of sulindac prevents tumors and restores enterocyte apoptosis in a murine model of familial adenomatous polyposisCarcinogenesis198791CrossRefPubMedGoogle Scholar
  9. 9.
    Waddell, WR, Loughry, RW 1983Sulindac for polyposis of the colonJ Surg Oncol248387PubMedGoogle Scholar
  10. 10.
    Cruz-Correa, M, Hylind, LM, Romans, KE,  et al. 2002Long-term treatment with sulindac in familial adenomatous polyposis: a prospective cohort studyGastroenterology122641645PubMedGoogle Scholar
  11. 11.
    Matsuhashi, N, Nakajima, A, Fukushima, Y,  et al. 1997Effects of sulindac on sporadic colorectal adenomatous polypsGut40344349PubMedGoogle Scholar
  12. 12.
    Esaki, M, Matsumoto, T, Mizuno, M, Kobori, Y,  et al. 2002Effect of sulindac treatment for attenuated familial adenomatous polyposis with a new germline APC mutation at codon 161: report of a caseDis Colon Rectum4513971402CrossRefPubMedGoogle Scholar
  13. 13.
    Sandler, RS, Halabi, S, Baron, JA,  et al. 2003A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancerNew Engl J Med348883890PubMedGoogle Scholar
  14. 14.
    Benamouzig, R, Deyra, J, Martin, A,  et al. 2003Daily soluble aspirin and prevention of colorectal adenoma recurrence: 1-year results of the APACC trialGastroenterology125328336CrossRefPubMedGoogle Scholar
  15. 15.
    Takayama, T, Katsuki, S, Takahashi, Y,  et al. 1998Aberrant crypt foci of the colon as precursors of adenoma and cancerNew Engl J Med33912771284CrossRefPubMedGoogle Scholar
  16. 16.
    Thun, MJ, Namboodiri, MM, Heath, CW 1991Aspirin use and reduced risk of fatal colon cancerN Engl J Med32515931596PubMedGoogle Scholar
  17. 17.
    Steinbach, G, Lynch, PM, Phillips, RKS,  et al. 2000The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposisNew Engl J Med34219461952CrossRefPubMedGoogle Scholar
  18. 18.
    Higuchi, T, Iwama, T, Yoshinaga, K,  et al. 2003A randomized, double-blind, placebo-controlled trial of the effects of rofecoxib, a selective cyclooxygenase-2 inhibitor, on rectal polyps in familial adenomatous polyposis patientsClin Cancer Res947564760PubMedGoogle Scholar
  19. 19.
    Wakitani, K, Nanayama, T, Masaki, M,  et al. 1998Profile of JTE-522 as a human cyclooxygenase-2 inhibitorJpn J Pharmacol78365371CrossRefPubMedGoogle Scholar
  20. 20.
    Sasai, H, Masaki, M, Wakitani, M 2000Suppression of polypogenesis in a new mouse strain with a truncated ApcΔ474 by a novel COX-2 inhibitor, JTE-522Carcinogenesis21953958CrossRefPubMedGoogle Scholar
  21. 21.
    Japanese Society for Cancer of the Colon and Rectum1988General rules for clinical and pathological studies on cancer of the colon, rectum and anus (in Japanese)6th ed.KaneharaTokyo64Google Scholar
  22. 22.
    Fenwick, SW, Toogood, GJ, Lodge, PA,  et al. 2003The effect of the selective cyclooxygenase-2 inhibitor rofecoxib on human colorectal cancer liver metastasesGastroenterology125716729CrossRefPubMedGoogle Scholar
  23. 23.
    Seseko, S, Umemura, K, Nakashima, M 2003Pharmacokinetics and safety of JTE-522 in Japanese healthy male and female volunteers (in Japanese)Jpn J Clin Pharmacol Ther34201202SGoogle Scholar
  24. 24.
    Ladenheim, J, Garcia, G, Titzer, D,  et al. 1995Effect of sulindac on sporadic colonic polypsGastroenterology10810831087CrossRefPubMedGoogle Scholar
  25. 25.
    Giardiello, FM, Yang, VW, Hylind, LM,  et al. 2002Primary chemoprevention of familial adenomatous polyposis with sulindacNew Engl J Med34610541059CrossRefPubMedGoogle Scholar
  26. 26.
    Baron, JA, Cole, BF, Sandler, RS,  et al. 2003A randomized trial of aspirin to prevent colorectal adenomasN Engl J Med348891899CrossRefPubMedGoogle Scholar
  27. 27.
    Suleiman, S, Rex, DK, Sonnenberg, A 2002Chemoprevention of colorectal cancer by aspirin: a cost-effectiveness analysisGastroenterology1227887CrossRefPubMedGoogle Scholar
  28. 28.
    Bodenheimer, T 2000Uneasy alliance—clinical investigators and the pharmaceutical industryN Engl J Med3421539154PubMedGoogle Scholar

Copyright information

© The Japan Society of Clinical Oncology 2006

Authors and Affiliations

  • Takeo Iwama
    • 1
  • Takayuki Akasu
    • 2
  • Joji Utsunomiya
    • 3
  • Tetsuichiro Muto
    • 4
  1. 1.Department of SurgeryKyoundo Hospital, Sasaki InstituteTokyoJapan
  2. 2.Department of Colorectal SurgeryNational Cancer Center HospitalTokyoJapan
  3. 3.Junshin Familial Cancer InstituteTokyoJapan
  4. 4.Cancer Institute HospitalJapanese Foundation for Cancer ResearchTokyoJapan

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