Table 2.
List of selected lung cancer chemoprevention trials listed in the review.
| Class of Chemopreventive Agents | Chemopreventive Agent | Trial | Suboplulation of Patients | Reported Outcomes |
|---|---|---|---|---|
| Vitamins and minerals | ⍺-tocopherol, β-carotene | ATBC Study (Finland, 1994) | 29, 133 male smokers (≥ 5 cigarettes/day) | 17% increase in the lung cancer rate and 8% increase in the overall death rate [91]. The follow-up study showed reduction in the risk of those who quitted smoking [92]. |
| β-carotene, retinol | CARET Study (USA, 1985) | 18,344 current and ex-smokers, male and female; workers with history of asbestos exposure | Study was stopped 21 months earlier due to the higher incidence of lung cancer, higher rate of cardiovascular-related, mortality and overall mortality [93]. | |
| β-carotene | Physician’s Health Study (USA, 1982) | 22,071 male physicians, current smokers (11%) or former smokers (39%) | After 12 years, no effect was observed on any of the outcomes (malignant neoplasia, cardiovascular diseases, and death from all causes) [95] | |
| Selinium | The Nutritional Prevention of Cancer Trial | 1312 participants | Lung cancer was the secondary end point, with the pronounced benefit observed only in the subgroup with the low baseline of Se in serum [101]. | |
| Selinium | Secondary lung tumor prevention | 1772 patients with resected stage I non-small cell lung cancer | No chemoprevention benefit was observed [102] | |
| Phytochemicals | Green tea or polyphenon E | NCT00363805 (USA, 2004) | 195 patients, current or ex-smokers with Chronic Obstructive Pulmonary Disease | No results were published |
| Green tea, black tea | NCT02719860 High Tea Consumption on Smoking Related Oxidative Stress (USA, 2004) | 154 participants, current and ex-smokers | No results were published | |
| Glucobrassicin-rich Brussels sprouts | NCT0299939 Glucobrassicin-Brussel Sprout Effect on D10 Phe Metabolism (USA, 2016) | 48 participants, current and ex-smokers | Ongoing study | |
| Sulforaphane | NCT03232138 Clinical Trial of Lung Cancer Chemoprevention With Sulforaphane in Former Smokers | 72 participants, current and ex-smokers | Ongoing study | |
| Anti-innflammatory agents | Low-does aspirin (100 mg daily) | Women’s Health Study (USA, 1993) | 39,876 healthy female health professionals | No effect on lung cancer incidents [133] |
| NSAID’s and vitamin B | The VITamins And Lifestyle (Vital) Study | 77,738 men and women | No effect of pre-diagnostic use of aspirin on the survival rate in patients with lung cancer [202]. High use of ibuprofen was associated with the 64% increase in lung cancer mortality. | |
| Low (200 mg daily) and high (400 mg twice a day) doses of celecoxib | Biological activity of celecoxib in the bronchial epithelium of current and former smokers (USA, 2010) | 204 patients, smokers and former smokers | High-dose showed statistically significant reduction in Ki-67 expression in smokers (by 1.10%) and in former smokers (by 3.85%) [131] | |
| Celecoxib (400 mg daily) | Lung cancer chemoprevention with celecoxib in former smokers (USA, 2010) | 137 participants, former smokers (≥ 30-pack-years of smoking; ≥ of sustained abstinence of smoking) | Significant reduction in Ki-67 expression (up to 34%) in the celecoxib-arm. Beneficial results were linked with the higher levels of PGE2 in responders [82]. | |
| Iloprost | Effect of oral iloprost on endobronchial dysplasia in former smokers(USA, 2012) | 152 subjects with the sputum cytologic atypia (current and former smokers) | Significant improvement in biopsy data for former smokers, no effect was observed for current smokers [137]. | |
| Budenoside(1600μg daily for 6 months) | A randomized phase IIb trial of pulmicort turbuhaler (budesonide) in people with dysplasia of the bronchial epithelium. | 112 smokers with one or more sites of bronchial dysplasia | In smokers, inhaled budenoside showed no effect on regression of bronchial dysplastic lesions or prevention of new lesions [142]. | |
| Budenoside(800μg twice daily for 12 months) | Randomized phase II trial of inhaled budesonide versus placebo in high-Risk individuals with CT screen–detected lung nodules (USA, 2011) | 202 subjects, current and former smokers with CT-detected lung nodules that were persistent for at least 1 year | No effect was detected on lung nodules sizes, although per-lesion analysis showed effect on a regression of existing target nodules. No effect was observed for peripheral nodule sizes [143]. | |
| Triamcinolone, beclomethasone, flunisolide, fluticasone | Inhaled corticosteroids and risk of lung cancer among patients with chronic obstructive pulmonary disease. (USA, 2001) | 10,474 subjects with a diagnosis of COPD and no history of lung cancer | A dose-response decrease in risk of lung cancer was observed [144]. | |
| Fluticasone and budenoside | Effect of inhaled corticosteroids against lung cancer in female patients with COPD: a nationwide population-based cohort study (Taiwan, 2009) | 13,868 female COPD patients | A reduction of 1.5 fold in lung cancer incidence rate was observed in patients treated with the inhaled corticosteroids [145]. | |
| PPARγ agonists | Pioglitazone | A Randomized Phase II Trial of Pioglitazone for Lung Cancer Chemoprevention in High-Risk Current and Former Smokers (USA, 2019) | 92 subjects with the sputum cytologic atypia (current and former smokers) | Slight improvement in worst biopsy scores, dysplasia index, and average score was observed in former smokers. No protective effect was observed in current smokers [155]. |
| Modulators of mTOR pathways | Myo-inositol (18 g daily for 3 months) | A phase I study of myo-inositol for lung cancer chemoprevention (Canada, 2006) | 26 participants, smokers (≥ 30-pack-years of smoking) with one or more sites of bronchial dysplasia. Dose -escalation study had 16 participants, chemoprevention study was done in a group of 10 patients | Significant regression of dysplastic lesions was observed [177]. |
| Statins | Lovastatin, fluvastatin, rosuvastatin, simvastatin, atorvastatin, and pravastatin | A population-based cohort study to evaluate effect of stating against lung cancer in COPD patients (Taiwan, 2012) | 43,802 COPD patients | Statins, except lovastatin and fluvastatin, produce dose-dependent chemopreventive effect in studies COPD group of patients [184]. |
| Statins | A retrospective case-control study of US veterans evaluation the effect of statins on the risk of lung cancer in humans (USA, 2004) | 483,733 subjects | Statins showed protective effect against the development of lung cancer [185]. | |
| Antihypertensive agents | Angiotensin receptor blockers, diuretics beta-blockers, angiotensin-converting enzyme inhibitors and calcium channel blockers. | A retrospective cohort study to analyze an association between the use of angiotensin receptor blockers and cancer (UK, 2010) | 1,165,781 patients that were prescribed antihypertensive agents | Angiotensin receptor blockers, diuretics beta-blockers had no effect on the rate of lung cancer incidences. However, angiotensin-converting enzyme inhibitors and calcium channel blockers were associated with the higher incidences of lung cancer [189]. |
| Angiotensin receptor blockers | A retrospective nationwide cohort study: use of angiotensin receptor blockers and the risk of cancer (Denmark, 2006) | 107,466 ARB users (≥ 35 years) | No effect of Angiotensin receptor blockers on lung cancer incidences [188]. | |
| Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers | Population based cohort study to analyze an association between the use of angiotensin-converting enzyme inhibitors and cancer (UK, 2016) | 992,061 patients newly treated with any hypertensive agents. | Use of angiotensin-converting enzyme inhibitors was associated with the higher incidences of lung cancer [190]. |