Randomized, Placebo-Controlled, Esophageal Squamous Cell Cancer Chemoprevention Trial of Selenomethionine and Celecoxib

Limburg, Paul J.; Wei, Wenqiang; Ahnen, Dennis J.; Qiao, You‐Lin; Hawk, Ernest T.; Wang, Guoqing; Giffen, Carol; Wang, Guiqi; Roth, Mark J.; Lü, Ning; Korn, Edward L.; Ma, Yurong; Caldwell, Kathleen L.; Dong, Zheiwei; Taylor, Philip R.; Dawsey, Sanford M.

doi:10.1053/j.gastro.2005.06.024

Cited by 95 publications

(69 citation statements)

References 28 publications

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“…Our findings are in keeping with a recent report on chemoprevention of esophageal squamous cell cancer with another COX-2 inhibitor, celecoxib (21). In that study, treatment with celecoxib for up to 10 months had no effect on histologic grade of esophageal dysplasia.…”

Section: Discussionsupporting

confidence: 93%

Effects of Long-term Rofecoxib on Gastric Intestinal Metaplasia: Results of a Randomized Controlled Trial

Leung

Chan

et al. 2006

Clinical Cancer Research

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Purpose: Gastric cancer and its premalignant gastric lesion, intestinal metaplasia (IM), frequently express cyclooxygenase-2 (COX-2) at high levels. We tested whether long-term use of specific COX-2 inhibitors regress gastric IM. Experimental Design: This is a double-blind, randomized, placebo-controlled trial. Individuals with confirmed IM and Helicobacter pylori clearance were randomized to receive rofecoxib 25 mg daily or placebo. Endoscopy was done at baseline, at the end of year 1, and at the end of year 2, with multiple biopsies taken from the antrum and corpus. The primary end point was the proportion of subjects with regression of IM. Secondary end points were the severity of other histologic variables and the proportion of subjects with complete regression of IM. Results: Two-hundred and thirteen subjects with confirmed IM were randomized. The proportion of subjects with the regression of IM did not differ significantly between rofecoxib and placebo groups (antrum, 24.5% versus 26.9%; P = 0.74; corpus, 4.3% versus 2.2%; P = 0.68). Patients on rofecoxib (19.1%) and on placebo (16.1%) had no IM detected in the stomach (P = 0.59). There was also no significant difference in the severity of IM between the two treatment groups (P z 0.3). Conclusions: There was no trend to suggest that treatment with rofecoxib for 2 years resulted in the regression of gastric IM. Although our findings cast doubt on the reversibility of gastric IM by COX-2 inhibitor, further studies are needed to establish the role of COX-2 inhibitors in different stages of gastric carcinogenesis.

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Section: Discussionsupporting

confidence: 93%

Effects of Long-term Rofecoxib on Gastric Intestinal Metaplasia: Results of a Randomized Controlled Trial

Leung

Chan

et al. 2006

Clinical Cancer Research

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“…51 Although data are scarce on the efficacy of multivitamin and mineral supplement use in the primary prevention of cancer, evidence accumulated to date suggests their potential benefits in cancer prevention in persons with poor nutritional status. 52 In a randomized, controlled trial of selenomethionine (a synthetic form of organic selenium) and/or celecoxib among residents in a poorly nourished Chinese population (Linxian), Limburg et al 53 reported that neither selenomethionine nor celecoxib inhibited esophageal squamous carcinogenesis for high-risk subjects, but selenomethionine showed a protective effect among subjects with mild esophageal squamous dysplasia, thus providing the first report of a possible beneficial effect for any candidate esophageal SCC chemopreventive agent in a randomized controlled trial. In the earlier Linxian nutrition intervention trials of esophageal SCC, no significant reductions in the prevalence of esophageal or gastric dysplasia or cancer were seen with any of the 4 vitamin and mineral supplement groups that included zinc.…”

Section: Discussionmentioning

confidence: 99%

Prevention of upper aerodigestive tract cancer in zinc‐deficient rodents: Inefficacy of genetic or pharmacological disruption of COX‐2

Fong¹,

Jiang²,

Riley³

et al. 2007

Intl Journal of Cancer

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Zinc deficiency in humans is associated with an increased risk of upper aerodigestive tract (UADT) cancer. In rodents, zinc deficiency predisposes to carcinogenesis by causing proliferation and alterations in gene expression. We examined whether in zinc-deficient rodents, targeted disruption of the cyclooxygenase (COX)-2 pathway by the COX-2 selective inhibitor celecoxib or by genetic deletion prevent UADT carcinogenesis. Tongue cancer prevention studies were conducted in zinc-deficient rats previously exposed to a tongue carcinogen by celecoxib treatment with or without zinc replenishment, or by zinc replenishment alone. The ability of genetic COX-2 deletion to protect against chemically-induced forestomach tumorigenesis was examined in mice on zinc-deficient versus zinc-sufficient diet. The expression of 3 predictive biomarkers COX-2, nuclear factor (NF)-j B p65 and leukotriene A 4 hydrolase (LTA 4 H) was examined by immunohistochemistry. In zinc-deficient rats, celecoxib without zinc replenishment reduced lingual tumor multiplicity but not progression to malignancy. Celecoxib with zinc replenishment or zinc replenishment alone significantly lowered lingual squamous cell carcinoma incidence, as well as tumor multiplicity. Celecoxib alone reduced overexpression of the 3 biomarkers in tumors slightly, compared with intervention with zinc replenishment. Instead of being protected, zinc-deficient COX-2 null mice developed significantly greater tumor multiplicity and forestomach carcinoma incidence than wild-type controls. Additionally, zinc-deficient COX-22/2 forestomachs displayed strong LTA 4 H immunostaining, indicating activation of an alternative pathway under zinc deficiency when the COX-2 pathway is blocked. Thus, targeting only the COX-2 pathway in zinc-deficient animals did not prevent UADT carcinogenesis. Our data suggest zinc supplementation should be more thoroughly explored in human prevention clinical trials for UADT cancer. ' 2007 Wiley-Liss, Inc.Key words: zinc deficiency; upper aerodigestive tract cancer; chemoprevention; COX-2; COX-2 null mice Upper aerodigestive tract (UADT) cancer, including esophageal and oral cancer, is an important cause of morbidity and mortality worldwide. 1 With a 5-year survival of 10%, esophageal cancers are deadly. The prognosis of oral cancer, the major site being the tongue, is equally dismal, with an increasing incidence worldwide, particularly in young adults. 2 Patients with oral cancer have a high mortality rate, because of field cancerization effects that result in second primary tumors, particularly in the esophagus. 3,4 Thus, new chemopreventive and therapeutic approaches are much needed to prevent and treat these deadly cancers.While chronic alcohol consumption and tobacco use are the major risk factors for UADT cancer, epidemiologic and clinical studies have implicated dietary zinc deficiency (ZD) in the etiology of esophageal squamous cell carcinoma (SCC) and head and neck SCC. [5][6][7][8][9] In 2005, Abnet et al. 10 provided the strongest evidence of an a...

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“…In a randomized, placebo-controlled ESCC precancerous trial with selenomethionine and celecoxib for 10 months, selenomethionine improved squamous histology in 115 patients with mild dysplasia, but not in 125 patients with severe dysplasia (17). Celecoxib had no effect on the squamous histology.…”

Section: Etiology and Nutrition Intervention Studies Of Esophageal/ Gmentioning

confidence: 94%

Cancer Prevention Research in China

Yang

et al. 2015

Cancer Prevention Research

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Randomized, Placebo-Controlled, Esophageal Squamous Cell Cancer Chemoprevention Trial of Selenomethionine and Celecoxib

Cited by 95 publications

References 28 publications

Effects of Long-term Rofecoxib on Gastric Intestinal Metaplasia: Results of a Randomized Controlled Trial

Effects of Long-term Rofecoxib on Gastric Intestinal Metaplasia: Results of a Randomized Controlled Trial

Prevention of upper aerodigestive tract cancer in zinc‐deficient rodents: Inefficacy of genetic or pharmacological disruption of COX‐2

Cancer Prevention Research in China

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