Statins

We’re busy updating our review of statins and will provide a rating when that’s complete. While we’re working, we share a summary from our predecessor website, Beyond Conventional Cancer Therapies. The information we share here was last updated in August 2021.

Please consider supporting our update and revision to this information.

Statins

Key Points

• Before using this therapy, consult your oncology team about interactions with other treatments and therapies. Also make sure this therapy is safe for use with any other medical conditions you may have.
• Statins are a class of drugs approved by the FDA for several diseases and conditions.
• Use of statins in cancer prevention or treatment is considered “off-label.”
• Most of the evidence of statin use in cancer is from lab and animal studies and observational studies in humans. There are very few human clinical trials of statin use in cancer.
• Most researchers advise that more research is necessary to determine dosage, formulation, effectiveness and safety for use in cancer.
• BCCT’s interest in statins derives from laboratory and clinical anticancer effects including working against proliferation and angiogenesis, supporting apoptosis, and increasing cancer susceptibility to conventional treatment.
• Certain statins show promise in cancer prevention and treatment.
• Statins are approved for treating high cholesterol and are generally safe and usable long-term, although several cautions, potential side effects and interactions are noted.
• Serious side effects include permanent muscle damage and impaired cognitive function.
• Potential benefits in cancer must be weighed against the risks, and they should be discontinued promptly if serious side effects occur.
• Use statins under the supervision of a medical doctor who is experienced in prescribing and monitoring statins, particularly in patients with cancer.
• Some classes of statins may be more useful in cancer,or come with fewer serious side effects.
• Some integrative oncologists who use statins off-label also prescribe supplements—such as coenzyme Q10—to reduce the risk of muscle damage.

Statins are a class of cholesterol-lowering drugs being used off-label for cancer treatment by some integrative oncologists. Off-label use is a drug’s application for a disease or condition that has not yet received FDA approval. Every US state allows for drugs to be used off-label as long as there is enough evidence to support its use.

Statins are sub-classified as either more hydrophilic (tending to combine with or dissolve in water) or more lipophilic (tending to combine with or dissolve in lipids or fats).

The lipophilic statins are lovastatin, simvastatin, atorvastatin, fluvastatin and pitavastatin. The more hydrophilic statins are pravastatin and rosuvastatin. The more lipophilic statins especially have been associated with anticancer effects and cancer prevention.

CancerChoices sees statins as interesting and promising and is impressed with the early evidence to support re-purposing their use in cancer. At the same time, we are aware that statins can have serious side effects in some people. If you and your doctor are considering using these drugs off-label for your cancer, we urge you to weigh their potential benefits in treating your cancer against the risks.

Most reviewers suggest further study is needed before using statins in clinical practice as a cancer preventive or treatment.

Treating the Cancer

Working against cancer growth or spread, improving survival, or working with other treatments or therapies to improve their anticancer action

Clinical Evidence

General or Unspecified Cancers

Many studies of statins are observational, following people already taking statins to lower cholesterol and prevent heart disease. These patients tend to be older individuals with cardiovascular diseases or diabetes, who are more likely to be overweight and/or to smoke compared to patients who start taking statins only after a cancer diagnosis. These characteristics may explain why prediagnosis statin users have a poorer cancer prognosis.1 Observational studies in humans suggest the following effects of statins on cancer:

• Decreased risk of all-cause mortality compared with nonusers, with reduced cancer-specific mortality and improved progression-free survival, recurrence-free survival and disease-free survival who were taking statins before cancer diagnosis.2
• Postdiagnosis statin users gained significantly more recurrence-free survival benefit than prediagnosis statin users,3 and current users saw benefit, but not past users.4
• Improved survival among people with adenocarcinoma (may include breast, colorectal, lung, pancreatic and prostate cancers) with use at diagnosis. Post-diagnostic statin use was associated with prolonged survival in people, with greater benefit at higher doses.5

Breast Cancer

• Improved recurrence-free survival, cancer-specific survival, and/or overall survival6 including use after breast cancer diagnosis,7 although more uncertainty remains with post-diagnosis use8
• Lipophilic statins—particularly simvastatin—are especially associated with improved recurrence-free survival, overall survival, and cancer-specific survival in some reviews,9 but no difference was found in another10
• Improved three-year local recurrence-free survival in people with inflammatory breast cancer treated with postmastectomy radiation11

Antitumor properties:

• Clinical and epidemiological results show that statins may have anti-tumor potential.12
• Fluvastatin use reduced proliferation and increased cell death (apoptosis) in patients diagnosed with DCIS or stage 1 breast cancer with high grade (poorly differentiated) tumors.13

See Breast Cancer.

Colorectal Cancer

Improved survival or prognosis:

• Reduced all-cause and cancer-specific mortality with statin uses both before and after diagnosis in some reviews and meta-analyses14 and improved overall survival in a separate retrospective cohort review15 but no improvement in overall or progression-free survival in a randomized controlled trial16  or cohort study17
• Some studies and reviews found more benefit for specific people:
  • Benefit among current users, but not past users18
  • Benefit only for people with tumors with intact BMP signaling, independent of KRAS mutation status, when used after diagnosis19
• However, other reviews concluded that most studies were unable to improve progression-free survival and overall survival,20 perhaps due to poor trial design21
• Similar survival outcomes to patients mean BMI 24-25 treated with lifestyle modifications22
• Improved prognosis in large-scale cohort studies23

Antitumor action:

• Higher rate of tumor downstaging (reduction in the cancer stage) with use during neoadjuvant therapy24
• Lower median regression grade and higher likelihood of a better response25
• Better prognosis of surgically resected colorectal cancer in one review,26 although another study found no differences in disease-free survival, recurrence-free survival or all-cause mortality in patients undergoing neoadjuvant chemoradiotherapy and resection for rectal cancer27
• Reduced proportion of late-stage (at diagnosis) colorectal cancer cases among users of lipophilic statins in a large retrospective study of women28 and a population-based case-control study29
• A combination regimen of simvastatin, cetuximab and irinotecan showed promising safety and efficacy in KRAS-mutated colorectal cancer patients for whom irinotecan and oxaliplatin had failed.30

See Colorectal Cancer.

Kidney Cancer

• Improved cancer-specific and overall survival,31 among current users with diabetes32

See Kidney Cancer.

Leukemia

• No convincing evidence of effects to date33

See Leukemia.

Liver Cancer

• Lower risk of death in those with chronic viral hepatitis compared to hydrophilic (water-soluble) statins or no statins with lipophilic (fat-soluble) statins, with the most benefit was seen in those taking moderate doses of the statin for at least two years.34
• Improved survival of patients with advanced hepatocellular carcinoma35 or liver cancer36 with pravastatin

See Liver Cancer.

Lung Cancer

Improved survival:

• Decreased lung cancer-specific mortality37 in cohort studies, but not in case-control studies or randomized controlled trials38 with pravastatin39
• Improved recurrence-free survival40 but not progression-free survival41
• Effects with specific groups or treatments:
  • Improved progression-free survival in a subgroup of nonadenocarcinoma non-small cell lung cancer (NSCLC) patients prescribed simvastatin treated with gefitinib compared to patients prescribed gefitinib alone42 
  • Improved overall survival, cancer-specific survival and recurrence-free survival, especially with use after diagnosis or in stage IV lung cancer43
  • No improved survival with postmenopausal women44
  • Improved survival in patients undergoing surgery with lung adenocarcinoma with mutant p53, but worse prognosis of patients with wild type p5345
  • No impact on survival, recurrence or recurrence-free survival following curative resection with use at least one month before surgery and continued after surgery46
  • Improved 2-year loco-regional control but not survival among people with stage III NSCLC treated with definitive chemoradiation47
  • No improved survival for people with small-cell lung cancer with use at diagnosis48

Chemotherapy enhancer:

• Potentially enhanced the effects of tyrosine kinase inhibitors and chemotherapy on the overall survival of patients with non-small-cell lung cancer, but did not increase overall response rate and toxicity49

See Lung Cancer.

Lymphoma

• Non-Hodgkin’s lymphoma: no improved survival.50
• Burkitt lymphoma: improved survival with use at the time of diagnosis51
• Diffuse large B-cell lymphoma: no meaningful impact on prognosis when treated with rituximab plus CHOP therapy52

See Lymphoma.

Melanoma

• Delayed metastasis53

See Melanoma.

Multiple Myeloma

• Reduced all-cause and cancer-specific mortality54
• Improved progression-free survival, shortened response time for patients with relapsed or refractory multiple myeloma when lovastatin was added to treatment with thalidomide and dexamethasone55
• Reduced resistance to bortezomib and bendamustin with simvastatin,56 but did not reverse resistance to vincristine, adriamycin and dexamethasone (VAD)57
• No benefit, and possible harm regarding osteoclast activiry: no effect on bone turnover with high dose simvastatin for 7 days followed by a rest period of 21 days in two 4-week cycles, but transient stimulation of osteoclast activity58

See Multiple Myeloma.

Ovarian and Other Gynecologic Cancers

• Improved survival, especially with pre-diagnosis use59 but also with use after diagnosis60 among current users, but not past users61
• Effects with specific populations or treatments
  • Improved survival among ovarian cancer patients who underwent surgical resection, for both serous and non-serous histologies62
  • Improved survival with simvastatin among women with invasive epithelial ovarian cancer who were using statins before diagnosis63 
  • Improved survival, especially with atorvastatin or simvastatin, including in women who initiated lipophilic statins post-diagnosis64

See also Uterine Cancer below, plus handbooks on Cervical Cancer, Ovarian Cancer, Vaginal Cancer and Vulvar Cancer.

Pancreatic Cancer

• Improved overall and progression-free survival65
• Results with specific populations or treatments:
  • Improved survival among patients with low-grade (I or II), but not high-grade (III or IV) pancreatic adenocarcinoma66
  • Improved survival with both prior and active statin use, with a trend toward freedom from distant metastasis, in people with advanced-stage pancreatic adenocarcinoma67
  • Improved long-term response and overall survival with a history of statin treatment among people with unresectable pancreatic cancer who received two or more cycles of gemcitabine-erlotinib combination therapy as first-line palliative chemotherapy68
  • Improved survival among people newly diagnosed with pancreatic adenocarcinoma, especially with simvastatin or atorvastatin and patients with nonmetastatic pancreatic cancer69 
  • Improved survival among people with pancreatic ductal adenocarcinoma,70 especially with simvastatin or atorvastatin71

See Pancreatic Cancer.

Prostate Cancer

• Improved cancer-specific and all-cause survival with statin use.72 “If statin use is warranted for another indication, prolonged use, especially with a potent statin, may potentially decrease the risk of advanced prostate cancer or mortality associated with prostate cancer”,73 although one review suggests that use in treatment of prostate cancer is controversial74
• Reduced serum PSA in men when used for greater than 6 months, and especially when used for greater than 2 years75
• Results with specific populations or treatments:
  • Improved prostate cancer-specific survival, especially in advanced cancer and/or with radiation therapy76
  • Improved prostate cancer survival with use after diagnosis, especially in men managed with androgen deprivation therapy77 
  • Short-term treatment with atorvastatin reduced serum PSA level in a small prospective controlled clinical trial78

See Prostate Cancer.

Sarcoma

• Improved survival with bone/connective tissue cancer among current users, but not past users79

See Sarcoma.

Skin Cancer

• Improved survival in people with squamous-cell carcinoma patients with use following diagnosis, with greater benefit at higher doses80

See Skin Cancer.

Stomach (Gastric) Cancer

Improved survival among current users, but not past users81

See Stomach Cancer.

Uterine/Endometrial Cancer

• Improved overall survival,82 although no difference between statin users and nonusers in five-year recurrence-free survival, disease-specific survival or overall survival in a more recent study83
• Results with specific populations or treatments:
  • Improved survival among women with type 2 diabetes with non-endometrioid endometrial cancer84
  • Improved survival among women with primary endometrial cancer with postdiagnosis statin use, with use both before diagnosis and only after diagnosis85

See Uterine Cancer.

Clinical Trials

A few clinical trials have been conducted or are in progress.

• Several ongoing clinical trials are evaluating the effectiveness of statins as neoadjuvant therapy (therapy prior to a main therapy such as surgery) in postmenopausal breast cancer, prostate cancer and colorectal carcinoma. Encouraging clinical trial results suggest further study in these diseases:86
• Chronic lymphoblastic leukemia
• Multiple myeloma
• Pancreatic cancer
• Non small-cell lung cancer
• Small cell lung cancer
• Esophageal cancer
• Colorectal cancer

Modes of Action

Many observational and preclinical studies point to anticancer characteristics of statins:

• Inhibiting tumor growth
• Promoting programmed cell death
• Preventing the development of new blood vessels
• Preventing metastasis

All these processes play an important role in cancer causation, leading to oncologists’ interest in the role of statins in cancer prevention and treatment.87

Based on preclinical studies, researchers suggest that statins, through disturbing lipid metabolism, may influence pathways that signal cell growth and survival, thus leading to programmed cell death.88

The antineoplastic effect (inhibiting or preventing the growth and spread of tumors or malignant cells) of statins might also arise from a number of non-cholesterol-mediated mechanisms, such as immunoregulation, antioxidant activity and indirect anti-inflammatory properties.89

The anticancer effect of statins is a much more complex phenomenon and not only a result of their cholesterol-lowering effect.90

Lab and Animal Evidence

Findings in Specific Cancer Types

• Brain cancer: Anticancer effects have been seen on glioma cells in lab studies; however, whether these effects would be observed in animal and human trials remains uncertain.95
• Colorectal cancer:
  • Anticancer proliferation effects in resistant colorectal cancer cells when used with chemotherapy drugs; interfered with insulin-like growth factor 1 receptor (IGF-1R) signaling, which is known to promote cancer cell survival and proliferation; and other anticancer effects96
  • Only natural statins (simvastatin, mevastatin and lovastatin) suppressed NF-kB activation. NF-kB, a group of proteins that help control cell growth and survival, may be excessive or overactive in some types of cancer cells, which may lead to cancer cell growth.97
  • Pretreatment with lovastatin significantly increased cell death (apoptosis) induced by 5-fluorouracil (5-FU) or cisplatin in colon cancer cell lines.98
• Hematologic (blood) malignancies: A 2015 review of preclinical and clinical studies of statins as adjuvant (supplemental) therapies in hematologic malignancies concluded that statins provide anticancer effects.99 The same review found statins may restore chemosensitivity.100
• Prostate cancer: A 2017 review found statins sensitize cancer cells to radiation and show other potential antitumor effects in prostate cancer. Statins may possibly increase prostate cancer-specific survival.101
• Thyroid cancer:102
  • Statins have been associated with lower number and volume of thyroid nodules, greater cell death (apoptosis), and delayed metastasis, as well as potential protective effects on cancer progression.
  • Statins may interact with other therapies. The combination of lovastatin with the chemotherapy drug paclitaxel reduced the cell-killing ability of paclitaxel and inhibited cell death.

Managing Side Effects and Promoting Wellness

Managing or relieving side effects or symptoms, reducing treatment toxicity, supporting quality of life or promoting general well-being

Clinical Evidence

Cardiovascular Effects

• Reduced anthracycline-induced cardiotoxicity:103
  • Breast cancer patients receiving statins during anthracycline therapy had a lower risk of heart failure.
  • Statins were at least equally potent as dexrazoxane, beta-blockers or angiotensin antagonists in preventing anthracycline-induced cardiotoxicity.
  • Maintained left ventricular ejection fraction (LVEF) among patients receiving either high doses of atorvastatin or any statin during chemotherapy with doxorubicin or idarubicin for up to six months, while patients that did not receive the statin showed a significant decrease in LVEF.
• Reduced risk of stroke and combined risk of cardiovascular and cerebrovascular events from radiation to the chest, head or neck104

Other Side Effects

• Reduced anastomotic leaks (leaking where the colon segments were joined after removing the tumor) after elective colectomyIn colorectal cancer with use of statins near the time of surgery, but no difference in total complications or median hospital stay105 
• Decreased risk of a skeletal-related event in people with multiple myeloma106

Lab and Animal Evidence

Reducing Risk

Reducing the risk of developing cancer or the risk of recurrence

Statins may be useful in reducing risk of several types of cancer. In most of the human observational studies, statins were already being used by patients to lower cholesterol and to prevent heart disease:109

• Modest decrease in the risk of developing colorectal cancer
• Lower risk of advanced/aggressive prostate cancer
• Larger risk reductions for certain cancer types (such as gastric, oesophageal or hepatocellular) associated with statin use.
• Meta-analyses failed to show any difference in cancer risk between hydrophilic and lipophilic statins.

Some analyses conclude that the data are most convincing for simvastatin, with use for several years (greater than three years or greater than five years depending on the study) and in modest doses (up to 40 mg simvastatin, for example). The effect may be greater when combined with aspirin or other nonsteroidal anti-inflammatory drugs.110 

Other reviews found no convincing evidence of any impact of statin use on cancer incidence, neither decreasing nor increasing risk.111

Blood Cancers

(as a group)

• Reduced risk of blood cancers in observational studies, but not randomized control trials112 .

See also Leukemia, Lymphoma and Myeloma below

Brain Cancer

• Reduced risk of glioma113

See Brain, Spine and Nervous System Cancer.

Breast Cancer

Meta-analyses, reviews and case control studies:

• Reduced incidence of breast cancer in several investigations114 but not all115
• Decreased five-year breast cancer recurrence rates with initiatiion of statins less than three years after diagnosis of early stage breast cancer with lipophilic statins but not hydrophilic statins116

See Breast Cancer.

Colorectal Cancer

• Reduced risk of colorectal cancer in large epidemiological studies, but not always in randomized controlled studies, case control and cohort studies, perhaps because of shorter timeframes and confounding conditions, or perhaps because of publication bias in epidemiological studies117
• Mixed evidence regarding reduced risk of recurrent, multiple or advanced adenomas or adenomatous polyps118
• Results with specific populations or treatments:
  • Reduced risk for patients with diabetes or irritable bowel disease (IBD) with long-term use119
  • Lower risk of postcolonoscopy colorectal cancer, particularly for cancer in the lower colon120

Esophageal Cancer

• Some epidemiological evidence of prevention of adenocarcinoma of esophagus in patients with Barrett’s esophagus was found in a 2014 study. However, the authors conclude that sufficient clinical data is lacking, and thus “their use is justified only in patients with cardiovascular disease.”121
• Preliminary evidence of prevention of esophageal carcinoma is cited in a 2014 review.122

See Esophageal Cancer.

Gynecologic Cancer (Endometrial and Ovarian)

• Lab and animal studies suggest a chemopreventive role of statins.123

See Ovarian Cancer and Uterine Cancer.

Head and Neck Cancers

• Reduced incidence of head and neck cancers124

Kidney Cancer

• A preventive effect against kidney cancer in one 2014 review125 but not in a separate 2014 review and meta-analysis126

Leukemia

• Reduced risk of leukemia127

Liver Cancer

• Reviews have found preliminary and promising evidence of statins’ role in prevention,128 especially with simvastatin, lovastatin and atorvastatin.129
• Results with specific populations or treatments:
  • Preventive effect among patients with diabetes.130
  • Lower risk of developing liver cancer among people with with chronic viral hepatitis with use of lipophilic (fat-soluble) statins than use of hydrophilic (water-soluble) statins or no statins at all; for those taking lipophilic statins, the most benefit was seen in those taking moderate doses of the statin for at least two years.131

Lung Cancer

• Reduced lung cancer incidence with statin use132 irrespective of the presence of diabetes, smoking or alcohol use;133 however, a 2014 review concluded that recent studies fail to confirm a beneficial effect.134

Lymphoma

• Reduced risk of non-Hodgkin lymphoma135

Melanoma

• Prevention or delay by statins was noted in preclinical studies in a 2017 review.136 However,  no association was found in a 2014 review.137

Myeloma

• No reduced risk of myeloma in one review,138 but other investigations found lower risk with lipophilic statin, and specifically atorvastatin139 and more consistent protective associations across all latency periods among older patients140

Pancreatic Cancer

• Reduced risk of pancreatic cancer, although data are conflicting, possibly indicating a differential effect by sex, with prevention seen mainly in males.141

Prostate Cancer

• Some conclude that evidence of reduced risk of prostate cancer is inconclusive142 and use in prevention of prostate cancer is controversial.143 But others find reduced risk144145 and conclude that if statin use is warranted for another indication, prolonged use, especially with a potent statin, may potentially decrease the risk of advanced prostate cancer.”146
• Decreased risk of advanced or aggressive prostate cancer.147
• Decreased risk of recurrence after radiation therapy, although evidence of benefit in reducing recurrence is still limited148 but not radical prostatectomy, and only among men undergoing androgen deprivation therapy149

See Prostate Cancer.

Skin Cancer (Non-Melanoma)

Reduced skin cancer incidence with statin use150

Stomach (Gastric) Cancer

• Some evidence indicates statins may reduce the risk of gastric cancer both generally151 and specifically in diabetic patients.152

See Stomach Cancer.

Uterine Cancer

• Reduced risk of non-endometrioid endometrial cancer in women with type 2 diabetes153

Preclinical Evidence:

• Reduced colorectal cancer development in mice154

Optimizing Your Terrain

Creating an environment within your body that does not support cancer development, growth or spread

• Changes in gene expression following two weeks of use before breast cancer surgery155 specifically with high-dose atorvastatin156
• Anti-inflammatory effects influencing the tumor microenvironment and host inflammatory response157

Access

Statins oral form are available with a prescription at pharmacies. The dose and formulation varies by the specific statin prescribed. Some, such as lovastatin, are available in extended-release formulation.

Cautions

Some evidence indicates that statins may increase cancer risk in elderly patients, especially in association with hydrophilic statin use.158 A 2014 review concluded that “recent meta-analysis, however, showed no evidence of cancer increment in statin-treated elderly participants.”159 Some evidence indicates they may induce resistance to chemotherapy.160

Grade 3 or higher nausea and anorexia were noted slightly more often in patients with metastatic colorectal cancer in the simvastatin arm compared with with the placebo arm during treatment with XELIRI/FOLFIRI.161 Gastrointestinal side effects were also noted with high-dose simvastatin for people with multiple myeloma.162

Common Side Effects/Adverse Events

Side effects in conventional dosing to lower cholesterol:163

• Headache
• Difficulty sleeping
• Flushing of the skin
• Muscle aches, tenderness, or weakness (myalgia)
• Drowsiness
• Dizziness
• Nausea or vomiting
• Abdominal cramping or pain
• Bloating or gas
• Diarrhea
• Constipation
• Rash

Statins also carry warnings of the following possible side effects:164

• Memory loss
• Mental confusion
• High blood sugar
• Type 2 diabetes

Rare, but potentially serious side effects:165

• Myositis (inflammation of the muscles), the risk of muscle injury increases when certain other medications are taken with statins.
• Elevated levels of CPK (creatine kinase), a muscle enzyme that when elevated, can cause muscle pain, mild inflammation, and muscle weakness. This condition, though uncommon, can take a long time to resolve.
• Rhabdomyolysis (extreme muscle inflammation and damage). With this condition, muscles all over the body become painful and weak. The severely damaged muscles release proteins into the blood that collect in the kidneys. The kidneys can become damaged trying to eliminate a large amount of muscle breakdown caused by statin use. This can ultimately lead to kidney failure or even death. Fortunately, rhabdomyolysis is extremely rare.

“Statins should always be accompanied by CoQ-10 or ubiquinol” according to integrative oncologist and BCCT advisor Dwight McKee, MD.166 Integrative oncologist and BCCT advisor Keith Block, MD, concurs: “Because statins deplete coenzyme Q10 especially from your muscle cells, particularly your heart, I advise patients on statins to take at least 30 mg of coQ10 per day, and 200 mg or considerably more if they are taking any heart-damaging medications such as Adriamycin or Herceptin.”167   See further discussion in the Commentary section below.

In 2019, the FDA added statins to its list of drugs requiring evaluation for the need for regulatory action. The side effect in question is immune-mediated necrotising myopathy, characterized by “signs of necrosis, or cell death, in the muscles, which causes weakness and fatigue.”168 BCCT asked retired integrative oncologist and BCCT advisor Dwight McKee, MD, about the implications of this FDA evaluation and if people with autoimmune conditions were at increased risk for this side effect. See his reply in Commentary below.

“Although they have been observed, such side effects as insomnia and decrease in cognitive function are still questionable. It is very important for a pharmacist to suggest a less lipophilic member of the statin group when dealing with patients who have an existing or potential condition of insomnia or decreased cognitive function.”169

Thus a trade-off exists: the more lipophilic statins are considered to have greater anticancer potential but also greater risks for cognitive function. Therefore, potential benefits of statin use solely for anticancer purposes need to be carefully weighed for those with insomnia or at risk of decreased cognitive function.

Statins and Drug or Food Interactions

Statins may interact with drugs, causing potentially serious side effects including these:170

• Over-the-counter vitamins and dietary and herbal supplements
• Cholesterol lowering medications such as fibrates or nicotinic acid
• Certain antibiotics
• Birth control medications
• Warfarin (Coumadin), a blood thinner (the combination of statins and warfarin may cause blood to become too thin)
• Medications to treat HIV/AIDS
• Medications used to suppress the immune system.
• Grapefruit juice may decrease the ability of the liver to metabolize some statins, such as atorvastatin (Lipitor), simvastatin (Zocor), and lovastatin (Mevacor, Altocor); thus grapefruit juice should not be consumed at the same time as the statin medication is taken. Some doctors recommend avoiding any grapefruit juice.
• Pomegranate Juice: “Pomegranate juice may increase the risk of rhabdomyolysis for patients on statin therapy, possibly due to the inhibition of CYP 450 enzymes.”171
• Baicalin, an active constituent of skullcap, can decrease the blood level of statin drugs.172

Interactions increasing the risk of rhabdomyolysis (breakdown of muscle tissue that releases a damaging protein into the blood): “Rhabdomyolysis is probably the most serious statin side effect. Risk is increased when statins are co-administered with medications that inhibit their elimination. Due to differences among statins in elimination pathways, not all statins pose the same risk of drug interactions. Lovastatin, simvastatin, and to a lesser extent atorvastatin, have the most drug interactions.”173

Interaction with chemotherapy:

• One study found that use of lovastatin at the same time as paclitaxel interfered with paclitaxel’s cell-killing ability as well as cell death (apoptosis).174
• Because statins may interact with chemotherapy and other drugs, make sure your oncologist and primary care doctor know you are taking statins.

Checking for drug interactions:

• Clinicians can use the chart in the Canadian Pharmacist’s Letter to tailor medication choices to minimize risk.
• Patients can use the WebMD Interaction Checker to check for drug interactions.

Contraindications

Individuals with these situations should not use statins:175

• Allergic to statins or their ingredients
• Pregnant or planning a pregnancy
• Breastfeeding
• Active liver disease
• Drink excessive amounts of alcohol or are an alcoholic
• History of myopathy (a type of muscle disease)
• Renal failure due to rhabdomyolysis

Dosing

CancerChoices does not recommend therapies or doses, but only provides information for patients and providers to consider as part of a complete treatment plan. Patients should discuss therapies with their physicians, as contraindications, interactions and side effects must be evaluated.

Dosing of statins in conventional use varies depending on the particular statin prescribed.

The most effective dosing of statins for use in cancer treatment has not yet been established by randomized control clinical trials. At this time, no single statin agent and dose has been recommended for cancer prevention in the general population.176

Since most human studies have been observational of people already on statins for lowering cholesterol and other conditions, conventional doses were used. Some lab and animal studies suggest that higher doses may be needed for anticancer effects.177

The following reviews discuss doses of specific statin drugs used in cancer prevention and/or treatment studies:

• A 2014 review of therapeutic use of statins in several cancers178
• A 2001 trial of prevastatin in hepatocellular carcinoma179
• A 2016 review of DCIS or stage 1 breast cancer180
• Fluvastatin dosing in invasive breast cancer181

Integrative Programs, Protocols and Medical Systems

For more information about programs and protocols, see our Integrative Programs and Protocols page.

• Programs and protocols
  • Block program¹⁸² for inflammation
  • Chang strategies183
    • Liver cancer use as an adjuvant treatment
    • In cocktail treatment for both primary and secondary cancer prevention (preventing cancer occurrence as well as recurrence), especially for breast, colon, lung and prostate cancer

Commentary

Regarding concern for cognitive dysfunction with statin use, Gary Oberlender, MD, a geriatrician and consultant in geriatric care states: “Though the connection between statins and cognitive dysfunction has not been ‘proven’, that does not prove a lack of connection. The studies published have been too short and not well performed, in my view. However, there is abundant anecdotal evidence, including my own [clinical] experience, that strongly suggests that some, but certainly not all, people who take statins experience brain fog or other ill-defined cognitive symptoms. I think it has to do with too low LDL levels. In any event, I routinely recommend stopping statin drugs in persons experiencing cognitive symptoms, but only after a discussion with their primary care provider. I am not aware of evidence linking statin use with improved cognitive performance, though statins may reduce the risk of vascular dementia.”184

Retired integrative oncologist and BCCT advisor Dwight McKee, MD: It’s been known for a long time that statins can cause muscle inflammation, pain and weakness. In 2013 it was found that there is a subset of these side effects that are autoimmune mediated—that is, the person’s immune system reacts against the same enzyme target as the statins.[185 This happens in about 2-3 per 100,000 statin users, so it’s pretty rare. I think it probably should be added to the list, with that proviso that the incidence appears to be about 2-3 persons per 100,000 statin users.

I doubt there are any data, but the precautionary principle would certainly dictate that people with autoimmune disease avoid statins. When I was in practice, I used red yeast rice (RYR) that had adequate monokolin K content (which is identical to lovastatin. The pharmaceutical chemist who ‘invented’ lovastatin appears to have copied it from the yeast and knew of its long use in Chinese medicine for ‘excessive blood thickness’.) Several clinical studies in Asia have shown similar results in cancer control with RYR as with pharmaceutical statins.

I’ve never seen any of the typical statin side effects from red yeast rice, and it’s been shown to have similar anticancer effects as do statins. One problem however, is that in the US the FDA forbids RYR that contains monocolin K, since that’s a known ‘drug’ (lovastatin). In the European Union, the regulation is the opposite—manufacturers can’t make any health claims about red yeast rice UNLESS they have an adequate content of monocolin K.

The nutraceutical company that I formulate for (Life Plus International) has its major markets in Europe, where we sell a monocolin K rich RYR (took a while to find one with very low levels of citrinin, a mycotoxin that can develop during production–and high levels of citrinin often accompany low levels of monocolin K. Citrinin is nephrotoxic in animals, not tested in humans). I formulated it with 50 mg of Co-q-10 in each capsule. We can only sell it in the EU, however, where it’s required to have minimum 10 mg monocolin K per capsule to make the allowed health claims for red yeast rice.

In the US, there are a number of the professional line supplement companies that have intact monocolin K, despite the FDA rule. Thorne Research and several of the other professional supplement lines (used primarily by health care professionals) make red yeast rice (RYR) without removing the monocolin K, which is required for the cholesterol lowering effect. Other companies such as Metagenics and Designs for Health also do. Since these supplements are not FDA-approved drugs they don’t require a prescription. But the fact that doctors recommend these particular products seems to give them a bit more insulation from FDA than non-professional-line supplements. I would advise against buying RYR in a drug store or health food store, as FDA does not regulate for citrinin content. Consumer lab.com, a private company that analyzes and publishes their findings on many RYR products, found low levels of monocolin K, and substantial levels of the mycotoxin citirinin in many OTC brands of RYR.

I think it’s always a good idea to take Co Q10 (or the reduced form, ubiquinol) with RYR, since inhibition of the enzyme HMG COA reductase (the target of statins, and also the target of the autoimmune response that can be triggered by taking statins), also prevents the body’s ability to produce Co Q10.

Uses of Statins Off-Label for Cancer

What some researchers and clinicians are saying:

Integrative oncologist and BCCT advisor Keith Block, MD, wrote in his 2009 book: “A 2007 trial suggested that a statin may overcome drug resistance in multiple myeloma. So if a patient has multiple myeloma and is out of options, I would certainly consider as one option prescribing a statin for her alongside her drug protocol, in hopes of overcoming resistance and initiating a response.”186

Raymond Chang, MD, FACP, medical director of the Meridian Medical Group, writes: “Based on the large volume of research, the benefits of statin use appear to outweigh the potential risks. Still, patients should discuss statin use with a healthcare professional and take the drug only as directed.“187

Pon et al. in a 2015 review: “If statin use is warranted for another indication, prolonged use, especially with a potent statin, may potentially decrease the risk of advanced prostate cancer or mortality associated with prostate cancer.”188

Henninger and Fritz: “Off-label use of statins or novel Rac1 inhibitors might represent a promising pharmacological approach to gain control over chronic cardiotoxicity by interfering with key mechanisms of anthracycline-induced cardiomyocyte cell death.”189

Wang et al.: “Studies seem to suggest that statins may be protective and are not likely to be harmful in the setting of cancer, suggesting that cancer patients who already take statins should not have this medication discontinued.”190

Integrative oncologist and BCCT advisor Dwight McKee, MD, among others, concludes that “because most of the statins have patents that are expired or near expiration, there is a lack of incentive on the part of drug companies to conduct large scale clinical trials using these agents against cancer, so it is not clear that we will gain much more useful clinical insight in the near future, but strong reasons to consider adding statins to most cancer preventative or treatment cocktails unless side-effects are an issue in an individual patient.

“Notwithstanding occasional contradictory reports of statins increasing the risk of cancer, given the safety (simvastatin is available as an OTC in the U.K.) and low cost of statins, plus the wide array of studies and accumulating data showing a protective effect of statins against cancer development and recurrence, statins should be seriously considered as part of a cocktailed approach for primary and secondary cancer prevention (especially for colon, breast, lung and prostate—where the data are strongest).

“Statins should also be seriously considered as a cornerstone ingredient to combine synergistically with other compounds such as gamma tocotrienols, cox-2 inhibitors, bisphosphonates etc for added effects in cancer treatment. Not all statins are the same however, and some (e.g. lipophilic statins such as simvastatin) may work better against certain cancers than others (e.g. hydrophilic statins such as pravastatin). Dosage may be important as well.”193

Also known by these names

• HMG-CoA reductase inhibitors
• Generic and brand names available in the US:
  • Atorvastatin (Lipitor)
  • Pitavastatin (Livalo)
  • Fluvastatin (Lescol, Lescol XL)
  • Lovastatin (Mevacor, Altoprev)
  • Simvastatin (Zocor)
  • Pravastatin (Pravachol)
  • Rosuvastatin (Crestor)

Helpful links

• Chang R. Beyond the Magic Bullet: The Anti-Cancer Cocktail. New York: Square One Publishers. 2012. p. 104-105.
• Block KI. Life Over Cancer. New York: Bantam Dell. 2009. p. 522.
• Clinical trial using statins for cancer are listed at clinicaltrials.gov.
• Healthline: Red Yeast Rice: Benefits, Side Effects and Dosage
• Moss Reports podcast: Repurposed Drugs for Cancer with Raymond Chang, MD
• LifeExtension Nutritional Support: Cancer Adjuvant Therapy: Repurposing Common Drugs as Adjuvant Cancer Therapies
• Block KI, Block PB, Gyllenhaal C: Integrative Treatment for Colorectal Cancer
• Dwight McKee, MD, editor: Clinical Pearls

References

1. Mei Z, Liang M et al. Effects of statins on cancer mortality and progression: a systematic review and meta-analysis of 95 cohorts including 1,111,407 individuals. International Journal of Cancer. 2017 Mar 1;140(5):1068-1081.
2. He Y, Li X et al. Statins and multiple noncardiovascular outcomes: umbrella review of meta-analyses of observational studies and randomized controlled trials. Annals of Internal Medicine. 2018 Oct 16;169(8):543-553.
3. Mei Z, Liang M et al. Effects of statins on cancer mortality and progression: a systematic review and meta-analysis of 95 cohorts including 1,111,407 individuals. International Journal of Cancer. 2017 Mar 1;140(5):1068-1081; Zhong S, Zhang X et al. Statin use and mortality in cancer patients: systematic review and meta-analysis of observational studies. Cancer Treatment Reviews. 2015 Jun;41(6):554-67.
4. Wang A, Aragaki AK et al. Statin use and all-cancer survival: prospective results from the Women’s Health Initiative. Journal of Clinical Oncology. 2015 May;33(15suppl):1506-1506.
5. Ung MH, MacKenzie TA, Onega TL, Amos CI, Cheng C. Statins associate with improved mortality among patients with certain histological subtypes of lung cancer. Lung Cancer. 2018 Dec;126:89-96.
6. Manthravadi S, Shrestha A, Madhusudhana S. Impact of statin use on cancer recurrence and mortality in breast cancer: a systematic review and meta-analysis. International Journal of Cancer. 2016 Sep 15;139(6):1281-8; Mansourian M, Haghjooy-Javanmard S et al. Statins use and risk of breast cancer recurrence and death: a systematic review and meta-analysis of observational studies. Journal of Pharmacy and Pharmaceutical Sciences. 2016;19(1):72-81. p. 74; Wu QJ, Tu C et al. Statin use and breast cancer survival and risk: a systematic review and meta-analysis. Oncotarget. 2015 Dec 15;6(40):42988-3004; Wang A, Aragaki AK et al. Statin use and all-cancer survival: prospective results from the Women’s Health Initiative. Journal of Clinical Oncology. 2015 May;33(15suppl):1506-1506.
7. Wu QJ, Tu C et al. Statin use and breast cancer survival and risk: a systematic review and meta-analysis. Oncotarget. 2015 Dec 15;6(40):42988-3004. p. 42299.
8. Murtola TJ, Visvanathan K, Artama M, Vainio H, Pukkala E. Statin use and breast cancer survival: a nationwide cohort study from Finland. PloS One. 2014 Oct 20;9(10):e110231.
9. Manthravadi S, Shrestha A, Madhusudhana S. Impact of statin use on cancer recurrence and mortality in breast cancer: a systematic review and meta-analysis. International Journal of Cancer. 2016 Sep 15;139(6):1281-8; Ahern TP, Lash TL, Damkier P, Christiansen PM, Cronin-Fenton DP. Statins and breast cancer prognosis: evidence and opportunities. Lancet Oncology. 2014 Sep;15(10):e461-8.
10. Mansourian M, Haghjooy-Javanmard S et al. Statins use and risk of breast cancer recurrence and death: a systematic review and meta-analysis of observational studies. Journal of Pharmacy and Pharmaceutical Sciences. 2016;19(1):72-81.
11. Lacerda L, Reddy JP et al. Simvastatin radiosensitizes differentiated and stem-like breast cancer cell lines and is associated with improved local control in inflammatory breast cancer patients treated with postmastectomy radiation. Stem Cells Translational Medicine. 2014 Jul;3(7):849-56.
12. Micallef D, Micallef S, Schembri-Wismayer P, Calleja-Agius J. Novel applications of COX-2 inhibitors, metformin, and statins for the primary chemoprevention of breast cancer. Journal of the Turkish German Gynecological Association. 2016 Dec 1;17(4):214-223. p. 221.
13. Garwood ER, Kumar AS et al. Fluvastatin reduces proliferation and increases apoptosis in women with high grade breast cancer. Breast Cancer Research and Treatment. 2010 Jan;119(1):137-44.
14. Li Y, He X, Ding Y, Chen H, Sun L. Statin uses and mortality in colorectal cancer patients: An updated systematic review and meta-analysis. Cancer Medicine. 2019;8(6):3305–3313; Zhong S, Zhang X et al. Statin use and mortality in cancer patients: systematic review and meta-analysis of observational studies. Cancer Treatment Reviews. 2015 Jun;41(6):554-67; Ling Y, Yang L et al. Prognostic significance of statin use in colorectal cancer: a systematic review and meta-analysis. Medicine (Baltimore). 2015 Jun;94(25):e908; Cai H, Zhang G, Wang Z, Luo Z, Zhou X. Relationship between the use of statins and patient survival in colorectal cancer: a systematic review and meta-analysis. PLoS One. 2015 Jun 1;10(6):e0126944; Gray RT, Coleman HG, Hughes C, Murray LJ, Cardwell CR. Statin use and survival in colorectal cancer: results from a population-based cohort study and an updated systematic review and meta-analysis. Cancer Epidemiology. 2016 Dec;45:71-81; He Y, Li X et al. Statins and multiple noncardiovascular outcomes: umbrella review of meta-analyses of observational studies and randomized controlled trials. Annals of Internal Medicine. 2018 Oct 16;169(8):543-553.
15. Mafiana RN, Al-Kindi MS, Mafiana N, Al Lawati AS, Al Moundhri M. Impact of metabolic syndrome diagnosis and its treatment on survival of colorectal cancer patients. Journal of Cancer Epidemiology. 2019;2019:6527457.
16. Lim SH, Kim TW et al. A randomised, double-blind, placebo-controlled multi-centre phase III trial of XELIRI/FOLFIRI plus simvastatin for patients with metastatic colorectal cancer. British Journal of Cancer. 2015 Nov 17;113(10):1421-6.
17. Gray RT, Loughrey MB et al. Statin use, candidate mevalonate pathway biomarkers, and colon cancer survival in a population-based cohort study. British Journal of Cancer. 2017 Jun 6;116(12):1652-1659.
18. Wang A, Aragaki AK et al. Statin use and all-cancer survival: prospective results from the Women’s Health Initiative. Journal of Clinical Oncology. 2015 May;33(15suppl):1506-1506. 
19. Voorneveld PW, Reimers MS et al. Statin use after diagnosis of colon cancer and patient survival. Gastroenterology. 2017 Aug;153(2):470-479.
20. Qu B, Qu H. The influence of statins on risk and patient survival in colorectal cancer. Journal of Clinical Gastroenterology. 2019;53(9):699–701; Krens LL, Simkens LH, Baas JM, et al. Statin use is not associated with improved progression free survival in cetuximab treated KRAS mutant metastatic colorectal cancer patients: results from the CAIRO2 study. PLoS One. 2014;9(11):e112201.
21. Fong W, To KKW. Drug repurposing to overcome resistance to various therapies for colorectal cancer. Cellular and Molecular Life Sciences. 2019;76(17):3383–3406.
22. Yokomichi H, Nagai A et al. Statin use and all-cause and cancer mortality: BioBank Japan cohort. Journal of Epidemiology. 2017 Mar;27(3S):S84-S91.
23. Joo MK, Park JJ, Chun HJ. Additional benefits of routine drugs on gastrointestinal cancer: statins, metformin, and proton pump inhibitors. Digestive Diseases. 2018;36(1):1-14.
24. Gash KJ, Chambers AC, Cotton DE, Williams AC, Thomas MG. Potentiating the effects of radiotherapy in rectal cancer: the role of aspirin, statins and metformin as adjuncts to therapy. British Journal of Cancer. 2017 Jul 11;117(2):210-219.
25. Mace AG, Gantt GA et al. Statin therapy is associated with improved pathologic response to neoadjuvant chemoradiation in rectal cancer. Diseases of the Colon & Rectum. 2013 Nov;56(11):1217-27.
26. Qu B, Qu H. The influence of statins on risk and patient survival in colorectal cancer. Journal of Clinical Gastroenterology. 2019;53(9):699–701.
27. Fransgaard T, Hallas J, Thygesen LC, Gögenur I. Association of statin use and oncological outcomes after neoadjuvant radiotherapy in patients with rectal cancer. Anticancer Research. 2019;39(4):2177–2182.
28. Rutledge BP, Desai P et al. The association between statins and colorectal cancer stage in the Women’s Health Initiative. Molecular and Clinical Oncology. 2019;11(3):252–258.
29. Coogan PF, Smith J, Rosenberg L. Statin use and risk of colorectal cancer. Journal of the National Cancer Institute. 2007;99(1):32–40.
30. Qu B, Qu H. The influence of statins on risk and patient survival in colorectal cancer. Journal of Clinical Gastroenterology. 2019;53(9):699–701.
31. Nayan M, Punjani N et al. Statin use and kidney cancer survival outcomes: a systematic review and meta-analysis. Cancer Treatment Reviews. 2017 Jan;52:105-116.
32. Nayan M, Macdonald EM et al. Medication use and survival in diabetic patients with kidney cancer: a population-based cohort study. Pharmacological Research. 2016 Nov;113(Pt A):468-474.
33. Shadman M, Mawad R et al. Idarubicin, cytarabine, and pravastatin as induction therapy for untreated acute myeloid leukemia and high-risk myelodysplastic syndrome. American Journal of Hematology. 2015 Jun;90(6):483-6; Advani AS, McDonough S et al. SWOG0919: A phase 2 study of idarubicin and cytarabine in combination with pravastatin for relapsed acute myeloid leukaemia. British Journal of Haematology. 2014 Oct;167(2):233-7.
34. Simon TG, Duberg AS et al. Lipophilic statins and risk for hepatocellular carcinoma and death in patients with chronic viral hepatitis: results from a nationwide Swedish population. Annals of Internal Medicine. 2019 Sep 3;171(5):318-327.
35. Kawata S, Yamasaki E et al. Effect of pravastatin on survival in patients with advanced hepatocellular carcinoma. A randomized controlled trial. British Journal of Cancer. 2001 Apr 6;84(7):886-91.
36. Chang, R. Beyond the Magic Bullet: The Anti-Cancer Cocktail. New York: Square One Publishers. 2012.
37. Saxena A, Becker D et al. Therapeutic effects of repurposed therapies in non-small cell lung cancer: what is old is new again. Oncologist. 2015 Aug;20(8):934-45;Yang J, Li C, Shen Y, Zhou H, Shao Y, Zhu W, Chen Y. Impact of statin use on cancer-specific mortality and recurrence: a meta-analysis of 60 observational studies. Medicine (Baltimore). 2020 Apr;99(14):e19596; Chen Y, Li X et al. Effects of statin exposure and lung cancer survival: a meta-analysis of observational studies. Pharmacological Research. 2019 Mar;141:357-365.
38. Xia DK, Hu ZG, Tian YF, Zeng FJ. Statin use and prognosis of lung cancer: a systematic review and meta-analysis of observational studies and randomized controlled trials. Drug Design, Development and Theory. 2019 Jan 23;13:405-422.
39. Seckl MJ, Ottensmeier CH et al. Multicenter, phase III, randomized, double-blind, placebo-controlled trial of pravastatin added to first-line standard chemotherapy in small-cell lung cancer (LUNGSTAR). Journal of Clinical Oncology. 2017 May;35(14):1506–1514.
40. Yang J, Li C, Shen Y, Zhou H, Shao Y, Zhu W, Chen Y. Impact of statin use on cancer-specific mortality and recurrence: a meta-analysis of 60 observational studies. Medicine (Baltimore). 2020 Apr;99(14):e19596; Chen Y, Li X et al. Effects of statin exposure and lung cancer survival: a meta-analysis of observational studies. Pharmacological Research. 2019 Mar;141:357-365.
41. Yang J, Li C, Shen Y, Zhou H, Shao Y, Zhu W, Chen Y. Impact of statin use on cancer-specific mortality and recurrence: a meta-analysis of 60 observational studies. Medicine (Baltimore). 2020 Apr;99(14):e19596; Xia DK, Hu ZG, Tian YF, Zeng FJ. Statin use and prognosis of lung cancer: a systematic review and meta-analysis of observational studies and randomized controlled trials. Drug Design, Development and Theory. 2019 Jan 23;13:405-422.
42. Saxena A, Becker D et al. Therapeutic effects of repurposed therapies in non-small cell lung cancer: what is old is new again. Oncologist. 2015 Aug;20(8):934-45.
43. Chen Y, Li X et al. Effects of statin exposure and lung cancer survival: a meta-analysis of observational studies. Pharmacological Research. 2019 Mar;141:357-365.
44. Wang A, Aragaki AK et al. Statin use and all-cancer survival: prospective results from the Women’s Health Initiative. Journal of Clinical Oncology. 2015 May;33(15suppl):1506-1506.
45. Nishikawa S, Menju T et al. Statins may have double-edged effects in patients with lung adenocarcinoma after lung resection. Cancer Management and Research. 2019 Apr 18;11:3419-3432.
46. Oh TK, Kim K et al. Impact of statin use on recurrence or survival after surgical curative resection of non-small cell lung cancer. Cancer Control. 2018 Jan-Mar;25(1):1073274818778000.
47. Iarrobino NA, Gill BS et al. The impact of serum glucose, anti-diabetic agents, and statin usage in non-small cell lung cancer patients treated with definitive chemoradiation. Frontiers in Oncology. 2018 Jul 27;8:281.
48. Ung MH, MacKenzie TA, Onega TL, Amos CI, Cheng C. Statins associate with improved mortality among patients with certain histological subtypes of lung cancer. Lung Cancer. 2018 Dec;126:89-96.
49. Xia DK, Hu ZG, Tian YF, Zeng FJ. Statin use and prognosis of lung cancer: a systematic review and meta-analysis of observational studies and randomized controlled trials. Drug Design, Development and Theory. 2019 Jan 23;13:405-422.
50. Ye X, Mneina A, Johnston JB, Mahmud SM. Associations between statin use and non-Hodgkin lymphoma (NHL) risk and survival: a meta-analysis. Hematological Oncology. 2017 Jun;35(2):206-214.
51. Brånvall E, Eloranta S, Ekberg S, Birmann BM, Smedby KE. Statin use and prognosis in 12,865 non-Hodgkin lymphoma patients treated in the rituximab-era. Hematological Oncology. 2017 Jun;35(2suppl):230–232.
52. Ennishi D, Asai H et al. Statin-independent prognosis of patients with diffuse large B-cell lymphoma receiving rituximab plus CHOP therapy. Annals of Oncology: Official Journal of the European Society for Medical Oncology. 2010 Jun;21(6):1217-1221. 
53. Kushchayeva Y, Jensen K, Burman KD, Vasko V. Repositioning therapy for thyroid cancer: new insights on established medications. Endocrine-Related Cancer. 2014 May 6;21(3):R183-94.
54. Sanfilippo KM, Keller J et al. Statins are associated with reduced mortality in multiple myeloma. Journal of Clinical Oncology. 2016 Nov 20;34(33):4008-4014.
55. Hus M, Grzasko N et al. Thalidomide, dexamethasone and lovastatin with autologous stem cell transplantation as a salvage immunomodulatory therapy in patients with relapsed and refractory multiple myeloma. Annals of Hematology. 2011 Oct;90(10):1161-6.
56. Chae YK, Yousaf M et al. Statins as anti-cancer therapy; can we translate preclinical and epidemiologic data into clinical benefit? Discovery Medicine. 2015 Dec;20(112):413-27.
57. van der Spek E, Bloem AC, Sinnige HA, Lokhorst H. High dose simvastatin does not reverse resistance to vincristine, adriamycin, and dexamethasone (VAD) in myeloma. Haematologica. 2007 Dec;92(12):e130-1.
58. Sondergaard TE, Pedersen PT et al. A phase II clinical trial does not show that high dose simvastatin has beneficial effect on markers of bone turnover in multiple myeloma. Hematological Oncology. 2009 Mar;27(1):17-22.
59. Gizzo S, Quaranta M, Nardelli GB, Noventa M. Lipophilic statins as anticancer agents: molecular targeted actions and proposal in advanced gynaecological malignancies. Current Drug Targets. 2015;16(10):1142-59; Khan MS, Fatima K, Rameez. Impact of statins on risk and survival of ovarian cancer. Journal of Gynecologic Oncology. 2015 Jul;26(3):240-1; Urpilainen E, Marttila M et al. Prognosis of ovarian cancer in women with type 2 diabetes using metformin and other forms of antidiabetic medication or statins: a retrospective cohort study. BMC Cancer. 2018 Jul 28;18(1):767; Verdoodt F, Kjaer Hansen M et al. Statin use and mortality among ovarian cancer patients: a population-based cohort study. International Journal of Cancer. 2017 Jul 15;141(2):279-286;Xie W, Ning L, Huang Y et al. Statin use and survival outcomes in endocrine-related gynecologic cancers: a systematic review and meta-analysis. Oncotarget. 2017;8:41508–41517.
60. Kobayashi Y, Banno K, Kunitomi H, Tominaga E, Aoki D. Current state and outlook for drug repositioning anticipated in the field of ovarian cancer. Journal of Gynecologic Oncology. 2019 Jan;30(1):e10.
61. Wang A, Aragaki AK et al. Statin use and all-cancer survival: prospective results from the Women’s Health Initiative. Journal of Clinical Oncology. 2015 May;33(15suppl):1506-1506.
62. Vogel TJ, Goodman MT, Li AJ, Jeon CY. Statin treatment is associated with survival in a nationally representative population of elderly women with epithelial ovarian cancer. Gynecologic Oncology. 2017 Aug;146(2):340-345.
63. Couttenier A, Lacroix O et al. Statin use is associated with improved survival in ovarian cancer: a retrospective population-based study. PloS One. 2017 Dec 19;12(12):e0189233.
64. Visvanathan K, Modur S, Artama M, Murtola T. Lipophilic statins show promise for treatment of epithelial ovarian cancer. Cancer Research. 2020 Aug;80(16suppl):5782-5782.
65. Abdel-Rahman O. Statin treatment and outcomes of metastatic pancreatic cancer: a pooled analysis of two phase III studies. Clinical and Translational Oncology. 2019 Jun;21(6):810-816. 
66. Amin S, Boffetta P, Lucas AL. The role of common pharmaceutical agents on the prevention and treatment of pancreatic cancer. Gut and Liver. 2016 Sep 15;10(5):665-71.
67. Iarrobino NA, Gill B, Bernard ME, Mishra MV, Champ CE. Targeting tumor metabolism with statins during treatment for advanced-stage pancreatic cancer. American Journal of Clinical Oncology. 2018 Nov;41(11):1125-1131.
68. Moon do C, Lee HS et al. Concomitant statin use has a favorable effect on gemcitabine-erlotinib combination chemotherapy for advanced pancreatic cancer. Yonsei Med J. 2016 Sep;57(5):1124-30.
69. Lee HS, Lee HS et al. Statin use and its impact on survival in pancreatic cancer patients. Medicine (Baltimore). 2016 May;95(19):e3607.
70. Kozak MM, Anderson EM, von Eyben R, Pai JS, Poultsides GA, Visser BC, Norton JA, Koong AC, Chang DT. Statin and metformin use prolongs survival in patients with resectable pancreatic cancer. Pancreas. 2016 Jan;45(1):64-70.
71. Huang BZ, Chang JI, Li E, Xiang AH, Wu BU. Influence of statins and cholesterol on mortality among patients with pancreatic cancer. Journal of the National Cancer Institute. 2016 Dec 31;109(5).
72. Pon D, Abe A, Gupta EK. A review of statin use and prostate cancer. Current Atherosclerosis Reports. 2015;17(2):474; Raval AD, Thakker D et al. Association between statins and clinical outcomes among men with prostate cancer: a systematic review and meta-analysis. Prostate Cancer Prostatic Dis. 2016 Jun;19(2):151-62; Larsen SB, Dehlendorff C et al. Postdiagnosis statin use and mortality in Danish patients with prostate cancer. Journal of Clinical Oncology. 2017 Oct 10;35(29):3290-3297.
73. Pon D, Abe A, Gupta EK. A review of statin use and prostate cancer. Current Atherosclerosis Reports. 2015;17(2):474.
74. Pisanti S, Picardi P, Ciaglia E, D’Alessandro A, Bifulco M. Novel prospects of statins as therapeutic agents in cancer. Pharmacological Research. 2014 Oct;88:84-98.
75. Mener, DJ. Prostate specific antigen reduction following statin therapy: mechanism of action and review of the literature. IUBMB Life. 2010 Aug;62(8):584-90.
76. Alfaqih MA, Allott EH, Hamilton RJ, Freeman MR, Freedland SJ. The current evidence on statin use and prostate cancer prevention: are we there yet? Nature Reviews. Urology. 2017 Feb;14(2):107-119.
77. Murtola TJ, Peltomaa AI et al. Statin use and prostate cancer survival in the Finnish randomized study of screening for prostate cancer. European Urology Focus. 2017 Apr;3(2-3):212-220.
78. Khosropanah I, Falahatkar S, Farhat B, Heidari Bateni Z, Enshaei A, Allahkhah AA, Khosropanah D. Assessment of atorvastatin effectiveness on serum PSA level in hypercholesterolemic males. Acta Med Iran. 2011;49(12):789-94.
79. Wang A, Aragaki AK et al. Statin use and all-cancer survival: prospective results from the Women’s Health Initiative. Journal of Clinical Oncology. 2015 May;33(15suppl):1506-1506.
80. Ung MH, MacKenzie TA, Onega TL, Amos CI, Cheng C. Statins associate with improved mortality among patients with certain histological subtypes of lung cancer. Lung Cancer. 2018 Dec;126:89-96.
81. Wang A, Aragaki AK et al. Statin use and all-cancer survival: prospective results from the Women’s Health Initiative. Journal of Clinical Oncology. 2015 May;33(15suppl):1506-1506.
82. Xie W, Ning L, Huang Y et al. Statin use and survival outcomes in endocrine-related gynecologic cancers: a systematic review and meta-analysis. Oncotarget. 2017;8:41508–41517.
83. Segev Y, Gemer O et al. An Israeli gynecologic oncology group study of statin use and endometrial cancer prognosis. International Journal of Gynaecology & Obstetrics. 2020 Jan;148(1):79-86.
84. Arima R, Marttila M et al. Antidiabetic medication, statins and the risk and prognosis of non-endometrioid endometrial cancer in women with type 2 diabetes. Anticancer Research. 2018 Jul;38(7):4169-4178.
85. Sperling CD, Verdoodt F et al. Statin use and mortality among endometrial cancer patients: a Danish nationwide cohort study. International Journal of Cancer. 2018 Dec 1;143(11):2668-2676.
86. Pisanti S, Picardi P, Ciaglia E, D’Alessandro A, Bifulco M. Novel prospects of statins as therapeutic agents in cancer. Pharmacological Research. 2014 Oct;88:84-98. p. 92.
87. Kubatka P, Kruzliak P, Rotrekl V, Jelinkova S, Mladosievicova B. Statins in oncological research: from experimental studies to clinical practice. Critical Reviews in Oncology/Hematology. 2014 Dec;92(3):296-311.
88. Apostolova SN, Toshkova RA, Momchilova AB, Tzoneva RD. Statins and alkylphospholipids as new anticancer agents targeting lipid metabolism. Anticancer Agents Med Chem. 2016;16(12):1512-1522.
89. Alfaqih MA, Allott EH, Hamilton RJ, Freeman MR, Freedland SJ. The current evidence on statin use and prostate cancer prevention: are we there yet? Nature Reviews. Urology. 2017 Feb;14(2):107-119.
90. Stryjkowska-Góra A, Karczmarek-Borowska B, Góra T, Krawczak K. Statins and cancers. Contemporary Oncology (Pozn). 2015;19(3):167-75.
91. Pisanti S, Picardi P, Ciaglia E, D’Alessandro A, Bifulco M. Novel prospects of statins as therapeutic agents in cancer. Pharmacological Research. 2014 Oct;88:84-98.
92. Yao H, He G et al. Triple-negative breast cancer: is there a treatment on the horizon? Oncotarget. 2017 Jan 3;8(1):1913-1924.
93. Manthravadi S, Shrestha A, Madhusudhana S. Impact of statin use on cancer recurrence and mortality in breast cancer: a systematic review and meta-analysis. International Journal of Cancer. 2016 Sep 15;139(6):1281-8.
94. Pisanti S, Picardi P, Ciaglia E, D’Alessandro A, Bifulco M. Novel prospects of statins as therapeutic agents in cancer. Pharmacological Research. 2014 Oct;88:84-98. p. 94.
95. Rundle-Thiele D, Head R, Cosgrove L, Martin JH. Repurposing some older drugs that cross the blood-brain barrier and have potential anticancer activity to provide new treatment options for glioblastoma. British Journal of Clinical Pharmacology. 2016 Feb;81(2):199-209.
96. Fong W, To KKW. Drug repurposing to overcome resistance to various therapies for colorectal cancer. Cellular and Molecular Life Sciences. 2019;76(17):3383–3406.
97. Ahn KS, Sethi G, Aggarwal BB. Reversal of chemoresistance and enhancement of apoptosis by statins through down-regulation of the NF-kappaB pathway. Biochemical pharmacology. 2008 Feb 15;75(4):907-13.
98. Agarwal B, Bhendwal S et al. Lovastatin augments apoptosis induced by chemotherapeutic agents in colon cancer cells. Clinical Cancer Research. 1999;5(8):2223–2229.
99. Bockorny B, Dasanu CA. HMG-CoA reductase inhibitors as adjuvant treatment for hematologic malignancies: what is the current evidence? Annals of Hematology. 2015 Jan;94(1):1-12.
100. Bockorny B, Dasanu CA. HMG-CoA reductase inhibitors as adjuvant treatment for hematologic malignancies: what is the current evidence? Annals of Hematology. 2015 Jan;94(1):1-12.
101. Hutchinson J, Marignol L. Clinical potential of statins in prostate cancer radiation therapy. Anticancer Research. 2017 Oct;37(10):5363-5372.
102. Kushchayeva Y, Jensen K, Burman KD, Vasko V. Repositioning therapy for thyroid cancer: new insights on established medications. Endocrine-Related Cancer. 2014 May 6;21(3):R183-94.
103. Henninger C, Fritz G et al. Statins in anthracycline-induced cardiotoxicity: Rac and Rho, and the heartbreakers. Cell Death & Disease. 2017 Jan 19;8(1):e2564.
104. Boulet J, Peña J et al. Statin use and risk of vascular events among cancer patients after radiotherapy to the thorax, head, and neck. Journal of the American Heart Association. 2019 Jul 2;8(13):e005996.
105. Qu B, Qu H. The influence of statins on risk and patient survival in colorectal cancer. Journal of Clinical Gastroenterology. 2019;53(9):699–701; Singh PP, Srinivasa S et al. Perioperative use of statins in elective colectomy. Diseases of the Colon & Rectum. 2012 Feb;55(2):205-10.
106. Sanfilippo KM, Keller J et al. Statins are associated with reduced mortality in multiple myeloma. Journal of Clinical Oncology. 2016 Nov 20;34(33):4008-4014.
107. Henninger C, Fritz G et al. Statins in anthracycline-induced cardiotoxicity: Rac and Rho, and the heartbreakers. Cell Death & Disease. 2017 Jan 19;8(1):e2564.
108. Henninger C, Fritz G et al. Statins in anthracycline-induced cardiotoxicity: Rac and Rho, and the heartbreakers. Cell Death & Disease. 2017 Jan 19;8(1):e2564.
109. Bonovas S. Statins: do they have a potential role in cancer prevention and modifying cancer-related outcomes? Drugs. 2014 Oct;74(16):1841-8.
110. Gronich N, Rennert G. Beyond aspirin–cancer prevention with statins, metformin and bisphosphonates. Nature Reviews. Clinical Oncology. 2013 Nov;10(11):625-42.
111. Kaye JA, Jick H. Statin use and cancer risk in the General Practice Research Database. British Journal of Cancer. 2004 Feb 9;90(3):635-7.
112. Yi X, Jia W, Jin Y, Zhen S. Statin use is associated with reduced risk of haematological malignancies: evidence from a meta-analysis. PLoS One. 2014 Jan 31;9(1):e87019; Pradelli D, Soranna D et al. Statins use and the risk of all and subtype hematological malignancies: a meta-analysis of observational studies. Cancer Medicine. 2015 May;4(5):770-80.
113. Pisanti S, Picardi P, Ciaglia E, D’Alessandro A, Bifulco M. Novel prospects of statins as therapeutic agents in cancer. Pharmacological Research. 2014 Oct;88:84-98.
114. Micallef D, Micallef S, Schembri-Wismayer P, Calleja-Agius J. Novel applications of COX-2 inhibitors, metformin, and statins for the primary chemoprevention of breast cancer. Journal of the Turkish German Gynecological Association. 2016 Dec 1;17(4):214-223. p. 221; Micallef D, Micallef S, Schembri-Wismayer P, Calleja-Agius J. Novel applications of COX-2 inhibitors, metformin, and statins for the primary chemoprevention of breast cancer. Journal of the Turkish German Gynecological Association. 2016 Dec 1;17(4):214-223. p. 221; Kochhar R, Khurana V, Bejjanki H, Caldito G, Fort C. Statins to reduce breast cancer risk: a case control study in US female veterans. Journal of Clinical Oncology. 2005 23:16_suppl, 514-514; Chae YK, Yousaf M et al. Statins as anti-cancer therapy; can we translate preclinical and epidemiologic data into clinical benefit? Discovery Medicine. 2015 Dec;20(112):413-27; Bonovas S, Filioussi K, Tsavaris N, Sitaras NM. Use of statins and breast cancer: a meta-analysis of seven randomized clinical trials and nine observational studies. Journal of Clinical Oncology. 2005 Dec 1;23(34):8606-12.
115. Islam MM, Yang HC et al. Exploring association between statin use and breast cancer risk: an updated meta-analysis. Archives of Gynecology and Obstetrics. 2017 Dec;296(6):1043-1053; Ahern TP, Lash TL, Damkier P, Christiansen PM, Cronin-Fenton DP. Statins and breast cancer prognosis: evidence and opportunities. Lancet Oncology. 2014 Sep;15(10):e461-8.
116. Kwan ML, Habel LA, Flick ED, Quesenberry CP, Caan B. Post-diagnosis statin use and breast cancer recurrence in a prospective cohort study of early stage breast cancer survivors. Breast Cancer Research and Treatment. 2008;109(3):573–579; Ahern TP, Pedersen L et al. Statin prescriptions and breast cancer recurrence risk: a Danish nationwide prospective cohort study. Journal of the National Cancer Institute. 2011;103(19):1461–1468.
117. Katona BW, Weiss JM. Chemoprevention of colorectal cancer. Gastroenterology. 2020;158(2):368–388; Joo MK, Park JJ, Chun HJ. Additional benefits of routine drugs on gastrointestinal cancer: statins, metformin, and proton pump inhibitors. Digestive Diseases. 2018;36(1):1-14; Dobrzycka M, Spychalski P et al. Statins and colorectal cancer—a systematic review. Experimental and Clinical Endocrinology & Diabetes. 2018;10.1055/a-0668-5692; Qu B, Qu H. The influence of statins on risk and patient survival in colorectal cancer. Journal of Clinical Gastroenterology. 2019;53(9):699–701; Krstic MN, Mijac DD, Popovic DD, Pavlovic Markovic A, Milosavljević T. General aspects of primary cancer prevention. Digestive Diseases. 2019;37(5):406–415; Lee JW, You NY et al. Statin use and site-specific risk of colorectal cancer in individuals with hypercholesterolemia from the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS). Nutrition, Metabolism & Cardiovascular Diseases. 2019;29(7):701–709; Ibáñez-Sanz G, Guinó E et al. Statin use and the risk of colorectal cancer in a population-based electronic health records study. Scientific Reports. 2019;9(1):13560; Lai SW, Kuo YH, Fang CW, Liao KF. Statins therapy and colorectal cancer risk. Nutrition, Metabolism & Cardiovascular Diseases. 2019;29(12):1429–1430; Cheung KS, Chen L et al. Statins reduce the progression of non-advanced adenomas to colorectal cancer: a postcolonoscopy study in 187 897 patients. Gut. 2019;68(11):1979–1985; Bonovas S. Statins: do they have a potential role in cancer prevention and modifying cancer-related outcomes? Drugs. 2014 Oct;74(16):1841-8; Gronich N, Rennert G. Beyond aspirin–cancer prevention with statins, metformin and bisphosphonates. Nature Reviews. Clinical Oncology. 2013 Nov;10(11):625-42; Pisanti S, Picardi P, Ciaglia E, D’Alessandro A, Bifulco M. Novel prospects of statins as therapeutic agents in cancer. Pharmacological Research. 2014 Oct;88:84-98; Broughton T, Sington J, Beales IL. Statin use is associated with a reduced incidence of colorectal cancer: a colonoscopy-controlled case-control study. BMC Gastroenterology. 2012 Apr 24;12:36; Lytras T, Nikolopoulos G, Bonovas S. Statins and the risk of colorectal cancer: an updated systematic review and meta-analysis of 40 studies. World Journal of Gastroenterology. 2014 Feb 21;20(7):1858-70; Lochhead P, Chan AT. Statins and colorectal cancer. Clinical Gastroenterology and Hepatology. 2013 Feb;11(2):109-18; quiz e13-4\; Bowles EJA, Yu O et al. Cardiovascular medication use and risks of colon cancer recurrences and additional cancer events: a cohort study. BMC Cancer. 2019;19(1):270; Dolejs SC, Gayed B, Fajardo A. Prevention of colorectal neoplasia. Clinics in Colon and Rectal Surgery. 2016;29(4):353-362; Wakeman C, Keenan J et al. Chemoprevention of colorectal neoplasia. ANZ Journal of Surgery. 2017 Dec;87(12):E228-E232; Chae YK, Yousaf M et al. Statins as anti-cancer therapy; can we translate preclinical and epidemiologic data into clinical benefit? Discovery Medicine. 2015 Dec;20(112):413-27; Coogan PF, Smith J, Rosenberg L. Statin use and risk of colorectal cancer. Journal of the National Cancer Institute. 2007;99(1):32–40; Singh H, Mahmud SM, Turner D, Xue L, Demers AA, Bernstein CN. Long-term use of statins and risk of colorectal cancer: a population-based study. American Journal of Gastroenterology. 2009 Dec;104(12):3015-23.
118. Katona BW, Weiss JM. Chemoprevention of colorectal cancer. Gastroenterology. 2020;158(2):368–388; Qu B, Qu H. The influence of statins on risk and patient survival in colorectal cancer. Journal of Clinical Gastroenterology. 2019;53(9):699–701; Liu Y, Tang W et al. Association between statin use and colorectal cancer risk: a meta-analysis of 42 studies. Cancer Causes Control. 2014 Feb;25(2):237-49; Pisanti S, Picardi P, Ciaglia E, D’Alessandro A, Bifulco M. Novel prospects of statins as therapeutic agents in cancer. Pharmacological Research. 2014 Oct;88:84-98; Broughton T, Sington J, Beales IL. Statin use is associated with a reduced incidence of colorectal cancer: a colonoscopy-controlled case-control study. BMC Gastroenterology. 2012 Apr 24;12:36; Samadder NJ, Mukherjee B et al. Risk of colorectal cancer in self-reported inflammatory bowel disease and modification of risk by statin and NSAID use. Cancer. 2011 Apr 15;117(8):1640-8.
119. Qu B, Qu H. The influence of statins on risk and patient survival in colorectal cancer. Journal of Clinical Gastroenterology. 2019;53(9):699–701.
120. Cheung KS, Chen L et al. Statins reduce the progression of non-advanced adenomas to colorectal cancer: a postcolonoscopy study in 187 897 patients. Gut. 2019 Feb 26. pii: gutjnl-2018-317714.
121. Tsibouris P, Vlachou E, Isaacs PE. Role of chemoprophylaxis with either NSAIDs or statins in patients with Barrett’s esophagus. World Journal of Gastrointestinal Pharmacology and Therapeutics. 2014 Feb 6;5(1):27-39.
122. Bonovas S. Statins: do they have a potential role in cancer prevention and modifying cancer-related outcomes? Drugs. 2014 Oct;74(16):1841-8.
123. Gizzo S, Quaranta M, Nardelli GB, Noventa M. Lipophilic statins as anticancer agents: molecular targeted actions and proposal in advanced gynaecological malignancies. Current Drug Targets. 2015;16(10):1142-59.
124. Chae YK, Yousaf M et al. Statins as anti-cancer therapy; can we translate preclinical and epidemiologic data into clinical benefit? Discovery Medicine. 2015 Dec;20(112):413-27.
125. Pisanti S, Picardi P, Ciaglia E, D’Alessandro A, Bifulco M. Novel prospects of statins as therapeutic agents in cancer. Pharmacological Research. 2014 Oct;88:84-98.
126. Zhang XL, Liu M et al. Statin use and risk of kidney cancer: a meta-analysis of observational studies and randomized trials. British Journal of Clinical Pharmacology. 2014 Mar;77(3):458-65.
127. Pradelli D, Soranna D et al. Statins use and the risk of all and subtype hematological malignancies: a meta-analysis of observational studies. Cancer Medicine. 2015 May;4(5):770-80.
128. Bonovas S. Statins: do they have a potential role in cancer prevention and modifying cancer-related outcomes? Drugs. 2014 Oct;74(16):1841-8; Ampuero J, Romero-Gomez M. Prevention of hepatocellular carcinoma by correction of metabolic abnormalities: role of statins and metformin. World Journal of Hepatology. 2015 May 18;7(8):1105-11; He Y, Li X et al. Statins and multiple noncardiovascular outcomes: umbrella review of meta-analyses of observational studies and randomized controlled trials. Annals of Internal Medicine. 2018 Oct 16;169(8):543-553; Chae YK, Yousaf M et al. Statins as anti-cancer therapy; can we translate preclinical and epidemiologic data into clinical benefit? Discovery Medicine. 2015 Dec;20(112):413-27.
129. Pisanti S, Picardi P, Ciaglia E, D’Alessandro A, Bifulco M. Novel prospects of statins as therapeutic agents in cancer. Pharmacological Research. 2014 Oct;88:84-98.
130. El-Serag HB, Johnson ML, Hachem C, Morgana RO. Statins are associated with a reduced risk of hepatocellular carcinoma in a large cohort of patients with diabetes. Gastroenterology. 2009 May;136(5):1601-8.
131. Simon TG, Duberg AS et al. Lipophilic statins and risk for hepatocellular carcinoma and death in patients with chronic viral hepatitis: results from a nationwide Swedish population. Annals of Internal Medicine. 2019 Sep 3;171(5):318-327.
132. Chae YK, Yousaf M et al. Statins as anti-cancer therapy; can we translate preclinical and epidemiologic data into clinical benefit? Discovery Medicine. 2015 Dec;20(112):413-27.
133. Khurana V, Bejjanki HR, Caldito G, Owens MW. Statins reduce the risk of lung cancer in humans: a large case-control study of US veterans. Chest. 2007 May;131(5):1282-8.
134. Pisanti S, Picardi P, Ciaglia E, D’Alessandro A, Bifulco M. Novel prospects of statins as therapeutic agents in cancer. Pharmacological Research. 2014 Oct;88:84-98.
135. Pradelli D, Soranna D et al. Statins use and the risk of all and subtype hematological malignancies: a meta-analysis of observational studies. Cancer Medicine. 2015 May;4(5):770-80; Cho SF, Yang YH et al. Previous exposure to statin may reduce the risk of subsequent non-Hodgkin lymphoma: a nationwide population-based case-control study. PLoS One. 2015 Oct 1;10(10):e0139289; Ye X, Mneina A, Johnston JB, Mahmud SM. Associations between statin use and non-Hodgkin lymphoma (NHL) risk and survival: a meta-analysis. Hematological Oncology. 2017 Jun;35(2):206-214; Wallace R, Anderson M et al. Prospective analysis of statin use and risk of non-Hodgkin’s lymphoma in the Women’s Health Initiative Cohort. Blood. 2013 Nov;122(21):4279..
136. Chhabra G, Ndiaye MA, Garcia-Peterson LM, Ahmad N. Melanoma chemoprevention: current status and future prospects. Photochemistry and Photobiology. 2017 Jul;93(4):975-989.
137. Pisanti S, Picardi P, Ciaglia E, D’Alessandro A, Bifulco M. Novel prospects of statins as therapeutic agents in cancer. Pharmacological Research. 2014 Oct;88:84-98.
138. Pradelli D, Soranna D et al. Statins use and the risk of all and subtype hematological malignancies: a meta-analysis of observational studies. Cancer Medicine. 2015 May;4(5):770-80.
139. Chiu BCH, Chen JH et al. Long term statin use and risk of multiple myeloma among 15.5 million Taiwanese adults: a retrospective cohort study. Blood. 2015 Dec;126(23):4198–4198.
140. Epstein MM, Divine G et al. Statin use and risk of multiple myeloma: an analysis from the cancer research network. International Journal of Cancer. 2017 Aug 1;141(3):480-487.
141. Pisanti S, Picardi P, Ciaglia E, D’Alessandro A, Bifulco M. Novel prospects of statins as therapeutic agents in cancer. Pharmacological Research. 2014 Oct;88:84-98; Amin S, Boffetta P, Lucas AL. The role of common pharmaceutical agents on the prevention and treatment of pancreatic cancer. Gut and Liver. 2016 Sep 15;10(5):665-71; Chae YK, Yousaf M et al. Statins as anti-cancer therapy; can we translate preclinical and epidemiologic data into clinical benefit? Discovery Medicine. 2015 Dec;20(112):413-27..
142. Babcook MA, Joshi A, Montellano JA, Shankar E, Gupta S. Statin use in prostate cancer: an update. Nutrition and Metabolic Insights. 2016 Jul 14;9:43-50; Bonovas S, Filioussi K, Sitaras NM. Statin use and the risk of prostate cancer: a metaanalysis of 6 randomized clinical trials and 13 observational studies. International Journal of Cancer. 2008 Aug 15;123(4):899-904. .
143. Pisanti S, Picardi P, Ciaglia E, D’Alessandro A, Bifulco M. Novel prospects of statins as therapeutic agents in cancer. Pharmacological Research. 2014 Oct;88:84-98; Pon D, Abe A, Gupta EK. A review of statin use and prostate cancer. Current Atherosclerosis Reports. 2015;17(2):474; Alfaqih MA, Allott EH, Hamilton RJ, Freeman MR, Freedland SJ. The current evidence on statin use and prostate cancer prevention: are we there yet? Nature Reviews. Urology. 2017 Feb;14(2):107-119..
144. Chae YK, Yousaf M et al. Statins as anti-cancer therapy; can we translate preclinical and epidemiologic data into clinical benefit? Discovery Medicine. 2015 Dec;20(112):413-27;
145. Moon H, Hill MM, Roberts MJ, Gardiner RA, Brown AJ. Statins: protectors or pretenders in prostate cancer? Trends in Endocrinology and Metabolism. 2014 Apr;25(4):188-96; Murtola TJ, Tammela TL et al. Prostate cancer and PSA among statin users in the Finnish prostate cancer screening trial. International Journal of Cancer. 2010 Oct 1;127(7):1650-9.
146. Pon D, Abe A, Gupta EK. A review of statin use and prostate cancer. Current Atherosclerosis Reports. 2015;17(2):474.
147. Bonovas S. Statins: do they have a potential role in cancer prevention and modifying cancer-related outcomes? Drugs. 2014 Oct;74(16):1841-8.
148. Pon D, Abe A, Gupta EK. A review of statin use and prostate cancer. Current Atherosclerosis Reports. 2015;17(2):474; Tan P, Wei S et al. The effect of statins on prostate cancer recurrence and mortality after definitive therapy: a systematic review and meta-analysis. Scientific Reports. 2016 Jul 7;6:29106.
149. Tan P, Wei S et al. The effect of statins on prostate cancer recurrence and mortality after definitive therapy: a systematic review and meta-analysis. Scientific Reports. 2016 Jul 7;6:29106.
150. Chae YK, Yousaf M et al. Statins as anti-cancer therapy; can we translate preclinical and epidemiologic data into clinical benefit? Discovery Medicine. 2015 Dec;20(112):413-27.
151. Bonovas S. Statins: do they have a potential role in cancer prevention and modifying cancer-related outcomes? Drugs. 2014 Oct;74(16):1841-8; Ma Z, Wang W, Jin G, Chu P, Li H. Effect of statins on gastric cancer incidence: a meta-analysis of case control studies. Journal of Cancer Research and Therapeutics. 2014 Oct-Dec;10(4):859-65.
152. Pisanti S, Picardi P, Ciaglia E, D’Alessandro A, Bifulco M. Novel prospects of statins as therapeutic agents in cancer. Pharmacological Research. 2014 Oct;88:84-98.
153. Arima R, Marttila M et al. Antidiabetic medication, statins and the risk and prognosis of non-endometrioid endometrial cancer in women with type 2 diabetes. Anticancer Research. 2018 Jul;38(7):4169-4178.
154. Katona BW, Weiss JM. Chemoprevention of colorectal cancer. Gastroenterology. 2020;158(2):368–388.
155. Bjarnadottir O, Kimbung S et al. Global transcriptional changes following statin treatment in breast cancer. Clinical Cancer Research. 2015 Aug 1;21(15):3402-11.
156. Feldt M, Bjarnadottir O et al. Statin-induced anti-proliferative effects via cyclin D1 and p27 in a window-of-opportunity breast cancer trial. Journal of Translational Medicine. 2015 Apr 29;13:133.
157. Pisanti S, Picardi P, Ciaglia E, D’Alessandro A, Bifulco M. Novel prospects of statins as therapeutic agents in cancer. Pharmacological Research. 2014 Oct;88:84-98.
158. Bonovas S. Statins: do they have a potential role in cancer prevention and modifying cancer-related outcomes? Drugs. 2014 Oct;74(16):1841-8.
159. Pisanti S, Picardi P, Ciaglia E, D’Alessandro A, Bifulco M. Novel prospects of statins as therapeutic agents in cancer. Pharmacological Research. 2014 Oct;88:84-98.
160. Ahmadi Y, Karimian R, Panahi Y. Effects of statins on the chemoresistance—the antagonistic drug-drug interactions versus the anti-cancer effects. Biomedicine and Pharmacotherapy. 2018 Dec;108:1856-1865.
161. Lim SH, Kim TW et al. A randomised, double-blind, placebo-controlled multi-centre phase III trial of XELIRI/FOLFIRI plus simvastatin for patients with metastatic colorectal cancer. British Journal of Cancer. 2015 Nov 17;113(10):1421-6.
162. Sondergaard TE, Pedersen PT et al. A phase II clinical trial does not show that high dose simvastatin has beneficial effect on markers of bone turnover in multiple myeloma. Hematological Oncology. 2009 Mar;27(1):17-22.
163. Beckerman J. Side effects of cholesterol-lowering statin drugs. WebMD. July 25, 2016. Viewed November 30, 2017.
164. Beckerman J. Side effects of cholesterol-lowering statin drugs. WebMD. July 25, 2016. Viewed November 30, 2017.
165. Beckerman J. Side effects of cholesterol-lowering statin drugs. WebMD. July 25, 2016. Viewed November 30, 2017.
166. McKee D. Questions about off-label drugs in oncology. Email communication with Laura Pole and others. September 2, 2020.
167. Block K. Life Over Cancer. New York: Bantam Dell. 2009. p. 522; Deichmann R, Lavie C, Andrews S. Coenzyme q10 and statin-induced mitochondrial dysfunction. Ochsner Journal. 2010;10(1):16-21.
168. Necrotizing Myopathy. The Myositis Association. Viewed November 13, 2019.
169. Motylev A. Lipophilic or hydrophilic nature of statins is important. Pharmacy Times. March 1, 2005. Viewed November 30, 2017.
170. Wedro B, Omudhome O. Statins (Cholesterol Drugs). eMedicineHealth. November 21, 2017. Viewed November 30, 2017.
171. Memorial Sloan Kettering Cancer Center. About Herbs: Pomegranate. December 19, 2017. Viewed August 17, 2018.
172. Fan L, Zhang W, Guo D, et al. The effect of herbal medicine baicalin on pharmacokinetics of rosuvastatin, substrate of organic anion-transporting polypeptide 1B1. Clin Pharmacol Ther. 2008 Mar;83(3):471-6. Viewed August 18, 2018.
173. Pharmacist’s Letter Detail-Document. Clinically Significant Statin Drug Interactions. Canadian Pharmacist’s Letter. March 2016. Viewed November 30, 2017.
174. Kushchayeva Y, Jensen K, Burman KD, Vasko V. Repositioning therapy for thyroid cancer: new insights on established medications. Endocrine-Related Cancer. 2014 May 6;21(3):R183-94.
175. Wedro B, Omudhome O. Statins (Cholesterol Drugs). eMedicineHealth. November 21, 2017. Viewed November 30, 2017.
176. May MB, Glode A. Novel uses for lipid-lowering agents. Journal of the Advanced Practitioner in Oncology. 2016 Mar;7(2):181-187.
177. Licarete E, Sesarman A, Banciu M. Exploitation of pleiotropic actions of statins by using tumour-targeted delivery systems. Journal of Microencapsulation. 2015;32(7):619-31.
178. Pisanti S, Picardi P, Ciaglia E, D’Alessandro A, Bifulco M. Novel prospects of statins as therapeutic agents in cancer. Pharmacological Research. 2014 Oct;88:84-98.
179. Kawata S, Yamasaki E et al. Effect of pravastatin on survival in patients with advanced hepatocellular carcinoma. A randomized controlled trial. British Journal of Cancer. 2001 Apr 6;84(7):886-91.
180. Micallef D, Micallef S, Schembri-Wismayer P, Calleja-Agius J. Novel applications of COX-2 inhibitors, metformin, and statins for the primary chemoprevention of breast cancer. Journal of the Turkish German Gynecological Association. 2016 Dec 1;17(4):214-223. p. 221.
181. Mansourian M, Haghjooy-Javanmard S et al. Statins use and risk of breast cancer recurrence and death: a systematic review and meta-analysis of observational studies. Journal of Pharmacy and Pharmaceutical Sciences. 2016.
182. Block KI. Life over Cancer: The Block Center Program for Integrative Cancer Treatment. New York: Bantam Dell. 2009.
183. Chang R. Beyond the Magic Bullet: The Anti-Cancer Cocktail. New York: Square One Publishers. 2012.
184. Oberlender G. Email communication with Laura Pole. November 19, 2018.
185. Hamann PD, Cooper RG, McHugh NJ, Chinoy H. Statin-induced necrotizing myositis – a discrete autoimmune entity within the “statin-induced myopathy spectrum.” Autoimmunity Reviews. 2013 Oct;12(12):1177-81.
186. Block K. Life Over Cancer. New York: Bantam Dell. 2009. p. 522.
187. Chang R. Beyond the Magic Bullet: The Anti-Cancer Cocktail. New York: Square One Publishers. 2012. p. 105.
188. Pon D, Abe A, Gupta EK. A review of statin use and prostate cancer. Current Atherosclerosis Reports. 2015.
189. Henninger C, Fritz G. Statins in anthracycline-induced cardiotoxicity: Rac and Rho, and the heartbreakers. Cell Death and Disease. 2017 Jan 19;8(1):e2564.
190. Wang A, Wakelee HA et al. Protective effects of statins in cancer: should they be prescribed for high-risk patients? Current Atherosclerosis Reports. 2016 Dec;18(12):72.
191. Obru O. Statins. MedicineNet. Viewed November 28, 2017.
192. Obru O. Statins. MedicineNet. Viewed November 28, 2017; Chang R. Beyond the Magic Bullet: The Anti-Cancer Cocktail. New York: Square One Publishers. 2012.
193. McKee D; Lecture: Off label pharmaceutical ‘cocktails’ for cancer treatment. Presentation at A4M Integrative Cancer Therapies, Module 6. June 6-8, 2013. Used with permission of Dwight McKee and Raymond Chang. Slides are available on request.