Chemoprevention of cancer

Chemoprevention of cancer

William N. William, Jr. MD equation Waun Ki Hong, MD equation Scott M. Lippman, MD


The field of cancer chemoprevention is underpinned by two phenomena of neoplasia: field carcinogenesis and multistep carcinogenesis. Accurate cancer risk models are critical to chemoprevention and may accelerate drug development in this setting. The Food and Drug Administration has approved several chemoprevention strategies. This chapter describes completed chemoprevention clinical trials focused on the four major cancer sites in the Western world (lung, colon and rectum, prostate, and breast), as well as site–agnostic chemoprevention studies. The contributions of vaccines to cancer prevention are also discussed.

Biology of chemoprevention

The field of cancer chemoprevention is underpinned by two phenomena of neoplasia: (1) field carcinogenesis, which is the multifocal development of intraepithelial neoplasia (IEN, or precancer) or the clonal spread of one or more IENs, and (2) multistep carcinogenesis, which is driven by genetic instability and accumulates progressive genetic and epigenetic changes.1–4 These processes spur evasion of apoptosis, strong replicative potential, and sustained angiogenesis leading to IEN and cancer development. Multistep carcinogenesis allows chemopreventive interventions at step(s) of neoplasia that precede invasive cancer. Drugs developed for cancer therapy can be examined for cancer chemoprevention because of important commonalities—including genetic and epigenetic abnormalities, loss of cellular control, and certain phenotypic characteristics—between cancer and multistep IEN.5 Field carcinogenesis makes approaches such as systemic agents attractive for controlling the neoplastic results of diffuse exposure to carcinogens throughout an epithelial field. The FDA has approved several treatments for IEN.

Cancer risk modeling

Accurate cancer risk models are critical to chemoprevention. Models based on clinical/demographic factors have been developed for breast cancer risk (Gail model) and lung cancer risk (Spitz model), and established identifiers of increased risk include precursor clinical/histologic lesions.6, 7 These risk models and lesions are useful on a population-wide basis but are less helpful in identifying individual or personalized risk. Recent work showed that clinical lung cancer risk models integrating genomics (somatic gene-expression arrays and host DNA-repair capacity) and metabolomics assessed risk more accurately than did the clinical models alone.8–10 Barrett’s esophagus is a well-established but modest predictor of absolute esophageal cancer risk, whereas a striking model incorporating certain loss of heterozygosity (LOH) and DNA-content profiles with Barrett’s distinguished between populations with a high (79% in 6 years) and low (0% in over 6 years) esophageal cancer risk.11 In oral leukoplakia, LOH at specific loci in chromosomes 3p and/or 9p confers a substantially increased risk of oral cancer (vs oral leukoplakia without such LOH)12–14 especially in patients with a previously treated oral cancer,15 and this marker was used as a selection criterion in the first and only personalized, molecularly based, randomized oral cancer chemoprevention trial completed till date—the Erlotinib Prevention of Oral Cancer study.16, 17 A high cancer risk is associated with a specific cyclin D1 genotype (adenine/guanine single-nucleotide polymorphism at position 870 of exon 4 of the cyclin D1 gene)18 in patients with dysplastic oral and/or laryngeal premalignant lesions. Recent work has shown that high cyclin D1 protein expression plus the high-risk cyclin D1 genotype further increased the cancer risk of laryngeal dysplasia patients.19 As such, selection of high-risk individuals for chemoprevention based on cancer risk modeling is considered a key factor to increase the therapeutic index of any given intervention, leading to successful drug development in this area.

Chemoprevention trials

This section describes completed chemoprevention clinical trials focused on the four major cancer sites in the Western world (lung, colon and rectum, prostate, and breast), as well as site-agnostic chemoprevention studies. The contributions of vaccines to cancer prevention are also discussed.

The lung


Clinical and translational chemoprevention trials, including five negative randomized trials of retinoids in smokers with metaplasia, have had little to no effect in reversing lung premalignancy.20 Despite the general negative results, encouraging phase IIb data have emerged from studies of 9-cis-retinoic acid modulation of RAR-β and Ki-6,21, 22 myo-inositol modulation of the PI3 kinase gene-expression pathway,23 budesonide modulation of computed tomography-detected peripheral nodules,24 and anethole dithiolthione25 and iloprost26 modulation of bronchial dysplasia.

Prevention of primary lung cancer

The National Cancer Institute-sponsored Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study was a phase III trial of α-tocopherol and β-carotene to prevent primary lung cancer. The ATBC study involved 29,133 male smokers between 50 and 69 years of age who had smoked an average of one pack of cigarettes a day for approximately 36 years.27 This trial’s 2 × 2 factorial design called for α-tocopherol (50 mg/day) and β-carotene (20 mg/day) to be given in a randomized, double-blind, placebo-controlled fashion. The factorial design allowed the study scientists to assess the individual effects of each agent. Significant increases in lung cancer incidence (18% increase, p = 0.01) and total mortality (8%, p = 0.02) occurred in the β-carotene-treated subjects after 6.1 years’ median follow-up. α-Tocopherol had no significant impact on the lung cancer mortality rate, and there was no evidence of an interaction between α-tocopherol and β-carotene.28

The Beta-Carotene and Retinol Efficacy Trial (CARET) tested the combination of β-carotene (30 mg/day) plus retinyl palmitate (25,000 IU/day) in 17,000 smokers and asbestos workers.29 It confirmed the major finding of the ATBC study with its primary finding that the β-carotene combination increased lung cancer risk in this high-risk population. There was no evidence from either the ATBC study or the CARET that β-carotene increased lung cancer risk in nonsmokers, or former or moderate (<1 pack a day) smokers.

SPT prevention

Two large-scale phase III retinoid trials have been completed in the setting of second primary tumor (SPT) prevention: one in Europe (investigating retinyl palmitate and/or N-acetyl-L-cysteine)31 and the other in the United States (investigating low-dose 13cRA).32 Neither demonstrated a reduction in SPT in the population overall. Selenium also failed to prevent SPTs compared with placebo in a RCT of 1151 patients with resected stage I nonsmall cell lung cancers.33

Colon and rectum

Colorectal trial designs have primarily employed the intermediate end points of adenomatous polyp development and response and hyperproliferation markers.

Sulindac and celecoxib can effectively treat (but not prevent) adenomas in individuals with familial adenomatous polyposis (FAP).34, 35 High-dose celecoxib (800 mg/day) reduced large-bowel polyposis by 28% and duodenal polyposis, which is difficult to resect, by 14% (vs placebo).36 These studies led to the interim FDA approval of celecoxib as an adjunct to endoscopic and surgical treatment of FAP patients. However, the labeled indication for polyp management in FAP patients was withdrawn due to challenges in conducting confirmatory trials in this high-risk setting. Calcium (1200 mg/day) reduced the risk of sporadic adenomas by 15% overall37 and even more in later-stage disease (vs placebo). The CAPP-1 and CAPP-2 trials examined aspirin (600 mg q.d.) in subjects with the hereditary colorectal cancer (CRC) syndromes of FAP and Lynch syndrome, respectively. CAPP-1 identified a nonsignificant reduction (23%) in polyp count and a trend toward reduced largest polyp size within the aspirin-treated group, after a median of 17 months of intervention. CAPP-2 found a significant reduction in risk of CRC (59%) only in subjects completing at least 2 years of intervention after a mean of 55.7 months of follow-up.38, 39

Four RCTs have tested the efficacy of aspirin in preventing sporadic adenomas, showing significant reductions in recurrent adenomas among patients treated for 1 or more years.40–43 There was no protective effect of aspirin on CRC risk in men and women in the Physician’s Health Study and Women’s Health Study (WHS). However, after an overall follow-up time of 18 years, recent results from the WHS indicate a significantly reduced risk for CRC in healthy women.44 Recent pooled analyses of the British Doctors Aspirin Trial and the UK Transient Ischaemic Attack Aspirin Trial found that aspirin was associated with a significant 26% reduction in CRC risk. The effect was greatest with at least 5 years treatment and did not appear for at least 10 years.45 The latter results are consistent with a recent, very large cohort study involving over 47,000 men from the Health Professionals Follow-up Study, which found a significant dose- and duration-related reduction in CRC risk.46

Three RCTs assessed coxibs (vs placebo) in preventing sporadic adenomas in patients with a prior history of colorectal polyps. The Adenomatous Polyp Prevention on Vioxx (APPROVe) trial tested rofecoxib, and various doses of celecoxib were tested in the APC and Prevention of Colorectal Sporadic Adenomatous Polyps (PreSAP) trials. Interim cardiovascular event rates were unexpectedly higher in APPROVe and APC but not PreSAP.47–49 The relevant data and safety monitoring committees stopped all three RCTs early because of these safety issues, despite significant activity against colorectal adenomas, and rofecoxib was withdrawn from the world market by the manufacturer. In APPROVe (2587 randomized subjects), rofecoxib reduced adenomas by 24%.50 In the APC (2035 randomized patients), adenoma rates were significantly different at 37.5% (celecoxib, 400 mg twice daily), 43% (celecoxib, 200 mg twice daily), and 60% (placebo) (p < 0.001)51; serious cardiovascular adverse event rates significantly increased in a dose-dependent manner. The PreSAP trial with 1561 randomized patients found incidences of adenomas of 33.6% (celecoxib, 400 mg once daily) and 49.3% (placebo) (p < 0.001).47 The risk of cardiovascular events did not increase in the PreSAP trial. In a recent extension analysis of APC patients, it appeared that the serious cardiovascular event rate wore off 2 years after stopping the drug and that a repression of adenomas persisted (albeit diminished), particularly for advanced adenomas. Results of a recent pooled analysis of the major celecoxib placebo-controlled trials (double-blind and planned follow-up of at least 3 years in nonarthritis disease settings) suggested that there was no increase in serious cardiovascular events at any studied dose (up to 400 mg b.i.d.) in people with a low-baseline cardiovascular risk (about 15–20% of people on these trials). These results strongly suggest that low-baseline cardiovascular risk can improve risk-benefit and help in selecting patients for future COX-2-specific NSAID (nonsteroidal anti-inflammatory drug) trials.52

Trials of vitamins and diet (low-fat, high fruits and vegetables and fiber) for reducing colorectal adenoma risk have had largely negative results.53, 54 Calcium reduced adenoma risk by a modest statistically significant 19%,37 which persisted in long-term follow-up.55 Two RCTs of folate showed no reduction in adenoma risk with a 0.5- or 1-mg/day dose; a subset analysis of one study suggested that folate (1 mg/day) may even increase the risk of advanced or multiple adenomas.43, 56

Preclinical studies of low doses of DFMO and sulindac supported an RCT of combined oral DFMO (500 mg) and sulindac (150 mg; vs placebo) for 36 months in 375 patients with a history of resected (≥3 mm) adenomas [stratified by use of low-dose aspirin (81 mg) at baseline and clinical adenoma site].57 Colorectal adenoma recurrence rates were as follows: one or more adenomas—41.1% placebo versus 12.3% (combination; relative risk (RR) 0.30; 95% confidence interval (CI), 0.18–0.49; p < 0.001); one or more advanced adenomas—8.5% (placebo) versus 0.7% (combination; RR 0.085; 95% CI, 0.011–0.65; p < 0.001); multiple adenomas—13.2% (placebo) versus 0.7% (combination; RR 0.055; 95% CI, 0.0074–0.41; p < 0.001). Combination chemoprevention has been long believed to have great potential for enhancing the activity and reducing the toxicity of active single agents, a belief that is reinforced by the landmark advance of this combination trial.

The breast

Based on highly significant positive results of the Breast Cancer Prevention Trial (BCPT), the selective estrogen-receptor modulator (SERM) tamoxifen became the first chemopreventive agent to earn FDA approval. Conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP), the BCPT compared tamoxifen with placebo in preventing breast cancer in 13,388 women at high-risk of this disease.58 The major high-risk eligibility criteria were age >60 years and history of lobular carcinoma in situ (LCIS), or women from 35 to 59 years old with 5-year breast cancer risk of 1.66% based on the Gail model. The actual overall average, 5-year baseline, breast cancer risk was 3.2%. At a median follow-up of 55 months, primary invasive breast cancer findings for the tamoxifen and placebo groups were 89 versus 175, respectively, for a 49% relative reduction (p < 0.00001). The relative breast cancer risk reduction was similar for all age and risk groups and was limited to ER (estrogen-receptor)-positive tumors. Tamoxifen nonsignificantly reduced overall and breast cancer mortality. Beneficial secondary findings included 19% fewer fractures in the tamoxifen group. Secondary adverse findings associated with tamoxifen were increased endometrial cancers, vascular events, and cataracts.

Although the BCPT successfully completed testing its primary hypothesis, it also raised several key unresolved issues, such as effects on mortality, optimal tamoxifen duration, generalizability of results, and the issue of prevention versus treatment. The FDA subsequently approved tamoxifen for breast cancer risk reduction in high-risk women. The FDA recommendation is 20 mg/day for 5 years for high-risk women and warns of tamoxifen-associated risks. The FDA also approved tamoxifen for reducing the incidence of contralateral breast cancers, based on consistent secondary adjuvant data.59

The NSABP B-24 study tested 5 years of tamoxifen (20 mg/day) versus placebo after resection and radiation in 1804 patients with ductal carcinoma in situ (DCIS).60 At a median follow-up of 74 months, 5-year incidences of all breast cancer events (invasive and noninvasive) were 8.2% and 13.4% in the tamoxifen and placebo groups, respectively, representing a 43% relative risk reduction (p = 0.0009). The cumulative incidence at 5 years of all invasive breast cancer events in the tamoxifen group was 4.1% versus 7.2% in the placebo group (p = 0.004). The FDA approved tamoxifen for risk reduction in the setting of locally treated (resection and radiation) breast DCIS.

The International Breast Cancer Intervention Study (IBIS-I) randomized 7410 women and showed a 32% reduction in breast cancer risk with tamoxifen.60 The positive results in this trial and the BCPT (the two stronger RCTs in this setting) were limited to ER-positive cancers. A report of the long-term follow-up of IBIS-I suggests that the beneficial tamoxifen effects on breast cancer risk reduction persist for at least 10 years, but most side effects resolve after the 5-year treatment period, including all serious adverse events (e.g., thrombotic events and endometrial cancer).61 These long-term findings have important implications for the risk/benefit profile of tamoxifen for prevention.

The Study of Tamoxifen and Raloxifene (STAR) tested the SERM raloxifene against its fellow SERM tamoxifen for better efficacy and lesser toxicity in breast cancer prevention.62 A total of 19,747 postmenopausal women with an increased risk of breast cancer were randomized to tamoxifen (20 mg/day) or raloxifene (60 mg/day) for 5 years. On long-term follow-up, raloxifene had slightly higher rates of invasive breast cancer (RR 1.24; 95% CI, 1.05–1.47), but produced fewer cases of uterine cancer than tamoxifen (RR 0.55; 95% CI, 0.36–0.83). Furthermore, the risks of thromboembolic events and cataracts were statistically significantly lower with raloxifene than with tamoxifen. Tamoxifen and raloxifene had similar effects in reducing noninvasive breast cancer.63 Raloxifene was approved by the FDA for invasive breast cancer risk reduction in postmenopausal women at a high such risk or with osteoporosis.

Following these seminal trials, the chemopreventive effect of third-generation SERMs was investigated. The Postmenopausal Evaluation and Risk-Reduction with Lasofoxifene Trial studied the effects of lasofoxifene in postmenopausal women with low bone mineral density (BMD),64, 65 showing a 79% reduction of invasive breast cancer and an 83% reduction in ER-positive breast cancer. A similar phase III prevention trial, known as the Generations Trial, reported a 56% decrease in invasive breast cancers in postmenopausal women with low BMD treated with arzoxifene.66, 67 These trials found that both lasofoxifene and arzoxifene reduce the risk of nonvertebral and vertebral fractures; however, these third-generation SERMs, like raloxifene and tamoxifen, still increase the risk of venous thromboembolic events.

A recent meta-analysis that included all nine of the large-scale phase III SERM prevention trials68 found that both overall and ER-positive breast cancer incidence is decreased by SERMs, and that DCIS incidence is decreased by all SERMs analyzed except raloxifene.

Based largely on results of the Anastrozole, Tamoxifen Alone or in Combination (ATAC) trial,69 there has been great interest in aromatase inhibitors for breast cancer prevention in postmenopausal women. The Mammary Prevention 3 trial randomized 4560 postmenopausal high-risk women to receive 25 mg of exemestane or placebo for 5 years. There was a 65% reduction in the annual incidence of invasive breast cancer in favor of exemestane (hazard ratio (HR) 0.35; 95% CI, 0.18–0.70). There were no differences between the groups in bone fractures, cardiovascular events, or other cancers.70 The IBIS-II trial evaluated anastrozole 1 mg daily versus placebo for 5 years in 3864 high-risk postmenopausal women and also demonstrated a reduction in the incidence in invasive breast cancer in favor of the aromatase inhibitor (HR 0.47; 95% CI, 0.32–0.68). Anastrozole also reduced the incidence of skin, gynecologic, gastrointestinal, and other cancers. More aches and pains, joint stiffness, vasomotor symptoms, dry eyes, and hypertension were seen in the anastrozole group, but there was no statistical significant difference in the incidence of fractures between the arms.71 To date, no agent has proven efficacy in the prevention of ER-negative breast cancer, although a number of drugs are under investigation.

The prostate

Prostate carcinogenesis is an androgen-driven process, and a large-scale RCT, the Prostate Cancer Prevention Trial (PCPT), tested finasteride (5 mg/day), which inhibits 5-α-reductase from converting testosterone into the more potent androgen dihydrotestosterone, versus placebo for 7 years in 18,882 men 55 years of age or older who had normal digital rectal exam (DRE) and prostate-specific antigen (PSA) level. Finasteride not only reduced the 7-year prostate cancer prevalence by 24.8%72 but also appeared to increase high-grade disease—6.4% (finasteride) versus 5.1% (placebo). Finasteride also reduced the risk of high-grade prostatic IEN.73 PCPT analyses also indicated a reduction in benign prostatic hypertrophy symptoms and an increase in sexual side effects, although a recent detailed analysis found that the effect of finasteride on sexual functioning was minimal.74 Secondary PCPT findings indicated a high risk of prostate cancer, including high-grade disease, among men with normal PSA levels75 and differences in PSA screening performance in men taking or not taking finasteride.76, 77 The adverse high-grade disease finding has sharply limited public interest in finasteride for prostate cancer prevention, and another major concern is that intensive PSA/DRE screening and early detection of prostate cancer in the PCPT could mean that finasteride may have prevented clinically “insignificant” more than “significant” prostate cancer. Several analyses, however, challenge these concerns.77–83 A recent long-term (18-year) follow-up report attempted to address the significance of the high-grade finding (e.g., finasteride-driven artifact vs new finasteride-induced high-grade cancers) and found no significant between-group difference in the rates of overall survival or survival after the diagnosis of prostate cancer.84

The Reduction by Dutasteride of Prostate Cancer Events study compared dutasteride 0.5 mg/day versus placebo in 8231 men 50–75 years of age, with a PSA level between 2.5 and 10 ng/mL and a negative prostate biopsy within 6 months. Participants underwent ultrasound-guided biopsies at years 2 and 4 of treatment. There was a 22.8% relative risk reduction in prostate cancer favoring dutasteride (95% CI, 15.2–29.8; p < 0.001). There were 29 and 19 cancers with Gleason scores of 8–10 in the dutasteride and placebo groups, respectively (p = 0.15) over years 1 through 4; however, during years 3 and 4, there were 12 tumors with Gleason scores of 8–10 in the dutasteride group, and only 1 in the placebo group (p = 0.003). Acute urinary retention was less frequent, but the composite end point of cardiac failure as well as erectile dysfunction and loss of libido was more common in the dutasteride group.85

Another very large RCT, the Selenium and Vitamin E Cancer Prevention Trial (SELECT), recently discontinued supplements and reported results demonstrating that selenium or vitamin E, alone or in combination, did not prevent prostate cancer at the doses and formulations used in a heterogeneous population of 35,533 relatively healthy men. A harmful trend for increased risk of prostate cancer in the vitamin E arm (p = 0.06; RR 1.13; 99% CI, 0.195–1.35)86 became statistically significant on further follow-up.87 A recent follow-on analysis of SELECT investigated whether selenium or vitamin E might benefit men with low-baseline selenium. Contrary to this hypothesis, there was no evidence of benefit of the intervention in the low-baseline selenium group; in fact, vitamin E supplementation actually increased the risk of total prostate cancer by 63% in men with low-baseline toenail selenium, and this effect was even stronger for high grade.88


The proof of principle of vaccinating against infection-related cancer was provided in Taiwan, where vaccinating children against hepatitis B has dramatically reduced the incidence and the mortality of liver cancer.89

HPV infection is an established major risk factor for cervical cancer, and molecular targeting through immunization against infections related to neoplasia is a very successful way to prevent early steps of host cell damage that otherwise can lead to cancer. The landmark advances of cancer chemoprevention are the relatively recent RCTs of HPV vaccines to prevent HPV infection in girls and young women and subsequent FDA approval of HPV vaccination in this setting.

The placebo-controlled (phase III) trial, Females United to Unilaterally Reduce Endo/Ectocervical Disease (FUTURE) I, evaluated the role of quadrivalent vaccine against HPV types 6, 11, 16, and 18 in preventing anogenital diseases in women aged 16–24 years. The co-primary composite end points were the incidence of genital warts, vulvar or vaginal IEN, or cancer and the incidence of cervical IEN, adenocarcinoma in situ, or cancer associated with HPV types 6, 11, 16, or 18 in a per-protocol susceptible population of women without virologic evidence of HPV infection. The vaccine efficacy was 100% for each of the co-primary end points.90 Similarly, the FUTURE II study found that the quadrivalent vaccine reduced the risk of the primary composite end point [cervical IEN (grades 2 and 3), adenocarcinoma in situ, or cancer-related to HPV types 16 or 18] by 98% in women between ages 15 and 26 years with no virologic evidence of HPV types 16 or 18.91 Another phase III trial tested a bivalent (HPV types 16 and 18) vaccine in 18,644 girls and women aged 15–25 years. The primary end point, grade 2 cervical IEN associated with HPV types 16 or 18, was reduced by 90% in women with no evidence of prior HPV infection.92 In a community-based, randomized, control trial in young women aged 18–25 years, the bivalent vaccine has been demonstrated to have high efficacy against HPV types 16 or 18 persistent infection and partial cross-protection against HPV types 31, 33, and 45.93

In males, the quadrivalent HPV vaccine has also been shown to reduce HPV infections and development of related external genital lesions,94 as well as anal IEN.95 Oral HPV infections are also reduced by HPV vaccination in women (bivalent vaccine), but it is unknown whether this will eventually translate into prevention of HPV-related head and neck squamous cell carcinomas.96 HPV vaccines have not been shown to accelerate HPV clearance and so are unlikely to prevent cancer in already infected patients.97

Overall cancer

Two important large US trials have tested the ability of β-carotene to reduce overall cancer incidence. The Physicians’ Health Study (PHS) was a 12-year test of β-carotene effects on overall cancer incidence.98 β-Carotene produced no significant differences in overall incidence of cancer (including lung cancer). Only 11% of this population were current smokers. Similar β-carotene results of the Women’s Health Study were reported.99 Recently, the results of the PHS II were reported. This large-scale (N = 14,641 men), randomized, placebo-controlled study demonstrated that daily low-dose multivitamin led to a statistically significant reduction in the incidence of total cancer compared with placebo (17.0 and 18.3 events, respectively, per 1000 person-years; HR 0.92, 95% CI, 0.86–0.998; p = 0.04), primarily in individuals with a prior cancer history. There were no reductions in the incidence of site-specific cancers.100 The clinical significance of this modest effect is yet to be determined.


Clinical cancer chemoprevention has matured with the FDA approvals of several agents to prevent cancer or to treat or prevent IEN, most recently raloxifene is used for preventing invasive breast cancer in high-risk women and HPV vaccine is used for anogenital cancer prevention. The current list of FDA-approved agents for cancer prevention includes diclofenac, Photofrin [in conjunction with photodynamic therapy (PDT)], tamoxifen, hepatitis B vaccine, bacillus Calmette–Guerin, valrubicin, masoprocol, 5-FU, aminolevulinic acid (with PDT), and HPV vaccine. Personalized approaches to identify patients most likely to benefit and least likely to be harmed by particular interventions are evolving from continued study of aspirin and celecoxib in colorectal neoplasia. One of the most promising current directions of cancer chemoprevention is combined agents. The concept that combinations can increase the ratio of benefit (activity) to risk (toxicity) for effective single agents received strong support from the stunning colorectal adenoma results of the DFMO-sulindac trial discussed earlier. Based on this trial, chemopreventive combinations may be at the threshold of becoming a standard clinical reality, and other active combinations should be moved into clinical trials.101


Cancer chemoprevention is beginning to add impressive data to the long list of advances resulting from cancer therapy. There have been several exciting developments in clinical chemoprevention, including, for example, the US Food and Drug Administration (FDA) approval of tamoxifen for reducing the risk of preinvasive and invasive breast cancer in the late 1990s, followed by subsequent FDA approvals of raloxifene for reducing the risk of invasive breast cancer and of human papillomavirus (HPV) vaccine for reducing cervical neoplasia risk. More recently, aromatase inhibitors have been shown to prevent breast cancers in postmenopausal women, with a favorable side effect profile. A randomized controlled trial (RCT) of combined sulindac and difluoromethylornithine (DFMO) achieved an extraordinary 70% reduction in colorectal adenomas (>90% in advanced adenomas) highlighting the chemoprevention focus on combined agents and signaling, perhaps the near realization of this approach in standard clinical practice.

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Apr 12, 2017 | Posted by in ONCOLOGY | Comments Off on Chemoprevention of cancer

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