Long-term treatment with sulindac in familial adenomatous polyposis: Is there an actual efficacy in prevention of rectal cancer?

Tonelli, Francesco; Valanzano, Rosa; Messerini, Luca; Ficari, Ferdinando

doi:10.1002/1096-9098(200005)74:1<15::aid-jso4>3.0.co;2-z

Cited by 68 publications

(57 citation statements)

References 31 publications

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“…In one prospective study, patients with FAP treated with sulindac maintained an antitumor response at a mean of 63.4 months of treatment (36). In another study, rectal adenomas regressed significantly during the first 6 months of sulindac use, but after a mean of f48 months of treatment both number and size of adenomas increased, showing no statistical difference with baseline values (37). Case reports also indicate that patients with FAP chronically maintained on sulindac for tumor suppression can develop invasive adenocarcinomas (38), an occurrence also seen in one of the Min/+ mice treated long-term with celecoxib (Fig.…”

Section: Discussionmentioning

confidence: 99%

Changes in Antitumor Response in C57BL/6J-Min/+ Mice during Long-term Administration of a Selective Cyclooxygenase-2 Inhibitor

Carothers¹,

Moran²,

Cho³

et al. 2006

Cancer Research

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Selective cyclooxygenase-2 (COX-2) inhibitors are widely prescribed for severe arthritis and are currently under study in human chemoprevention trials. Recently, long-term use of these agents has come under scrutiny due to reports of treatment-associated cardiovascular toxicity. On shortterm administration, the selective COX-2 inhibitor celecoxib inhibits adenoma growth in animal tumor models, including the C57BL/6J-Min/+ (Min/+) mouse. With uninterrupted longterm celecoxib administration, intestinal tumors in Min/+ mice initially regressed and then recurred to levels comparable with untreated controls. Celecoxib treatment initially suppressed COX-2 and prostaglandin E 2 (PGE 2 ) expression, but long-term use produced significantly higher levels of these molecules and reactivated PGE 2 -associated growth factor signaling pathways in tumor and normal tissues. These results indicate that COX-2 is an important chemoprevention target and that inhibition of this enzyme alters a paracrine enterocyte regulatory pathway. Chronic uninterrupted celecoxib treatment, however, induces untoward effects that enhance early progression events in intestinal tumorigenesis and may contribute to treatment toxicity. (Cancer Res 2006; 66(12): 6432-8)

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Section: Discussionmentioning

confidence: 99%

Changes in Antitumor Response in C57BL/6J-Min/+ Mice during Long-term Administration of a Selective Cyclooxygenase-2 Inhibitor

Carothers¹,

Moran²,

Cho³

et al. 2006

Cancer Research

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“…However, doses of sulindac 150-200 mg a day appeared ineffective. 88,95 A non-randomized controlled study showed the efficacy of rectal administration of sulindac 300 mg a day against rectal adenomas. 97 Also, indomethacin suppositories regressed rectal polyps in a non-controlled series of patients at a dose of 100 mg, but not 50 mg a day.…”

Section: Nsaids and Cox-2 Inhibitors For Colon Cancer Preventionmentioning

confidence: 99%

“…[39][40][41]43,49,78,[83][84][85][86][87][88][89][90][91][92][93][94][95][96][97] Endpoints are number and size of adenomas measured by flexible sigmoidoscopy or colonoscopy. All studies report complete or partial regression of adenomas after 3-6 months of treatment with sulindac 300-400 mg a day.…”

Section: Nsaids and Cox-2 Inhibitors For Colon Cancer Preventionmentioning

confidence: 99%

“…Also, reports about long-term administration of sulindac (Table 2) [93][94][95][96][97] showed (partial) regression of polyps during continuous treatment. In one investigation, sulindac reduced the number and size of polyps after 6 months, but not after prolonged treatment (12-124 months), 95 possibly because of the relative low dose of sulindac (200 mg per day) administered. Thus, 1.…”

Section: Nsaids and Cox-2 Inhibitors For Colon Cancer Preventionmentioning

confidence: 99%

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Chemopreventive Strategies Using NSAIDs and COX-2 Inhibitors

Keller¹,

Giardiello²

2003

Cancer Biology & Therapy

112

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“…Sulindac therapy is recommended in FAP patients after subtotal colectomy with IRA (48). However, rectal cancer has developed in patients in whom rectal polyps were effectively controlled with sulindac (49)(50)(51). In addition, sulindac appears to lack significant benefit in regressing duodenal adenomas (52) or preventing initial occurrence of adenomas in APC mutation carriers (primary prevention) (53).…”

Section: Chemoprevention Of Colon Cancermentioning

confidence: 99%

Recognition and management of hereditary colorectal cancer syndromes

Herraiz

Muñoz-Navas

2009

Rev. esp. enferm. dig.

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Over 1.900 colorectal tumors will arise in association with a hereditary colorectal cancer syndrome in Spain in 2009.The genetic defects responsible for the most common syndromes have been discovered in recent years.Genetic testing helps diagnose affected individuals and allows identification of individuals at-risk.Colonoscopy and prophylactic colectomy decrease colorectal cancer incidence and overall mortality in patients with hereditary colon cancer.Extracolonic tumors are frequent in these syndromes, so specific surveillance strategies should be offered.Key words: Familial adenomatous polyposis. Lynch syndrome. MYH-associated polyposis. Hereditary colon cancer. INTRODUCTIONIn 2009, it is estimated that around 38,000 people (1) in Spain will be diagnosed with colorectal cancer (CRC). Among these cases, more than 15% will exhibit familial clustering, and over 1,900 tumors (5%) will arise in association with a hereditary colorectal cancer syndrome. The most common hereditary colon cancer syndromes are: Familial Adenomatous Polyposis (FAP), attenuated FAP (AFAP), MYH associated polyposis (MAP), and Lynch syndrome, also known as Hereditary Non-Polyposis Colorectal Cancer syndrome (HNPCC) (2).During the last two decades, the most important advancement has been the identification of the genes that underlie these syndromes. This has permitted more accurate classifications of the various syndromes based upon genetic criteria, and consequently this has resulted in more tailored management strategies based on these criteria (3). The management of individuals with hereditary colon cancer or at-risk for hereditary colon cancer is dramatically different, so recognizing these syndromes is critical. Specifically, surveillance strategies for colon and extra-colonic tumors as well as surgical approaches (4) for the prevention and treatment of cancer reflect the heightened risks.This review is focused on current treatment strategies in hereditary colon cancer. It is important to recognize that "treatment" includes not only management of already diagnosed cancers but also to prevention of cancer in these high-risk populations. We first briefly summarize the major clinical features of each syndrome, including pattern of inheritance and penetrance, age at diagnosis and associated extra-colonic tumors. Familial adenomatous polyposis and attenuated FAPFAP is the most common adenomatous polyposis syndrome. Its prevalence is 1:5.000-10.000, with a uniform worldwide distribution, affecting both genders equally (5). Inherited in an autosomal dominant manner with a virtually penetrance of 100%, it is caused by a germline mutation in the Adenomatous Polyposis Coli (APC) tu- POINT OF VIEWmor suppressor gene on chromosome 5q21 (6). In 15-20%, the cases are "de novo" without clinical or genetic evidence of FAP in the parents (7). Recent studies indicate the presence of mosaicism in approximately 15% of such cases (8,9).Classic FAP is characterized by the development of hundreds to thousands of colorectal adenomas starting during the...

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Long-term treatment with sulindac in familial adenomatous polyposis: Is there an actual efficacy in prevention of rectal cancer?

Abstract: Sulindac appears to influence the morphological appearance of polyps in FAP patients, inducing apparent regression. However, at a dose of 200 mg, it does not influence the progression of polyps toward a malignant pattern.

Cited by 68 publications

References 31 publications

Changes in Antitumor Response in C57BL/6J-Min/+ Mice during Long-term Administration of a Selective Cyclooxygenase-2 Inhibitor

Changes in Antitumor Response in C57BL/6J-Min/+ Mice during Long-term Administration of a Selective Cyclooxygenase-2 Inhibitor

Chemopreventive Strategies Using NSAIDs and COX-2 Inhibitors

Recognition and management of hereditary colorectal cancer syndromes

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