Statins and Cancer: Myriad Trials Exploring Prevention, Mortality Reduction

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Can statins help prevent cancer and reduce mortality?
Can statins help prevent cancer and reduce mortality?

Do statins prevent cancer? Decrease risk of mortality? Prevent radiation damage?

Current data are equivocal but intriguing enough to warrant myriad clinical trials to determine the answer to these—and many other—questions in patients with different types of solid tumors as well as hematologic malignancies. 

At the recent annual meeting of the American Society of Clinical Oncology (ASCO), studies explored statin use in B-cell lymphoproliferative disorders, brain, breast, colorectal, ovarian, prostate and uterine malignancies, and small cell lung cancer.

The focus of each of the currently ongoing studies can be categorized as using statins to: 1) prevent cancer; 2) reduce cancer-mortality risk; 3) abate treatment toxicities; or 4) abrogate effects of cancer, such as deep vein thrombosis (DVT) or acute graft-versus-host disease (GVHD) in stem cell transplantation.

Statins for Cancer Prevention: Yes or No?

Epidemiologic data have suggested that in vitro effects observed with statins “might be more than just laboratory phenomena and might contribute to the prevention of human cancers,” Demierre and colleagues reported in the journal Nature in 2005. Statins are small-molecule inhibitors of 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase. 

Observational, preclinical, and randomized controlled studies of statins have all shown promise for cancer prevention. Specifically, preclinical studies of the effects of statins in both HMG-CoA reductase–dependent and independent pathways are “helping develop selective-targeting approaches for preventing cancer and several other aging-related diseases (for example, neurodegenerative disorders).”1

However, a meta-analysis published in JAMA in 2006 that investigated the effect of statin therapy on cancer incidence and cancer death reported, “statins have a neutral effect on cancer and cancer death risk in randomized controlled trials. We found that no type of cancer was affected by statin use and no subtype of statin affected the risk of cancer.” 

This analysis focused on breast, colon, gastrointestinal tract, prostate, respiratory tract, and skin cancers. The meta-analysis included 6,662 incident cancers and 2,407 cancer deaths. The odds ratio for reduction of cancer incidence was 1.02 (95% CI: 0.97-1.07) and, for cancer deaths, 1.01 (95% CI: 0.93-1.09).2

A recent study of the entire Danish population found that “statin use in persons without cancer, with the aim of reducing the risk of cardiovascular disease, does not influence cancer incidence or cancer-related mortality.”3

In addition, Nicole Nevadunsky, MD, a gynecologic oncologist at Montefiore Einstein Center for Cancer Care, Bronx, NY, who presented data from a retrospective analysis of the effects of statins on uterine malignancies at ASCO, told that “at present, there is not enough evidence to recommend statin use for primary prevention in women with a family history of endometrial cancer.”

A review of ongoing clinical trials of statins (Table 1) found only one prevention study: The National Surgical Adjuvant Breast and Bowel Project is conducting a phase 3 study of rosuvastatin versus placebo in patients with surgically removed stage I or II colorectal cancer to determine whether recurrence can be prevented.4 The results of this study may indicate whether or not there is potential for statins to prevent other cancers as well. # Sponsor
 Study Type  Cancer Primary Objective 
Ottawa Hospital Research Institute
 Phase 1 Advanced solid malignancies, with a focus on squamous cell carcinomas, NSCLC  Dose-finding study of high-dose rosuvastatin with erlotinib 
NCT01605344  University of North Carolina Lineberger Comprehensive Cancer Center  Phase 1  Colorectal  Effect of atorvastatin on PK profile of irinotecan and SN-38; safety in combination with FOLFIRI; safety of irinotecan with atorvastatin 
 NCT00583102  University of Iowa Phase 1, phase 2   Refractory or Relapsed AML  Safety and effectiveness of lovastatin with cytarabine
 NCT01733953  University of Minnesota Clinical and Translational Science Institute  Phase 2  Childhood ALL
Childhood NHL
 Effect of 6 months of statin therapy on conduit artery endothelial function in young adult survivors of childhood cancer
NCT01665677  West Virginia University   Phase 2 Hematological malignancies   Atorvastatin as GVHD prophylaxis for allogeneic HSCT
 NCT01524653 University of Vermont  Phase 2  Advanced cancers  Impact of rosuvastatin on risk markers of venous thromboembolism during systemic therapy for advanced cancer 
 NCT01525407  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium  Phase 2  Leukemias, lymphomas  Donor atorvastatin treatment for the prevention of severe acute GVHD in patients undergoing myeloablative peripheral blood stem cell transplantation
 NCT01299038 Beth Israel Deaconess Medical Center   Phase 2 Metastatic breast cancer  Determine if rosuvastatin lowers the number of tissue factor bearing microparticles, believed to be generated from cancer cells and may be a risk factor for DVT 

Virginia Commonwealth University

 Phase 2  Prostate cancer  Determine whether lovastatin protects against late effects of radiation therapy
NCT01831232   Fred Hutchinson Cancer Research Center  Phase 2 Acute myeloid leukemia or myelodysplastic syndromes   Determine cytostatic effect of idarubicin and cytarabine plus pravastatin
 NCT01561482  Baylor College of Medicine Phase 2  Prostate  Determine whether metformin and simvastatin can slow the speed of rise of PSA; stop its rise; or bring the level down 
 NCT01491958 Ohio State University Comprehensive Cancer Center   Phase 2  Acute myelogenous leukemia, acute lymphocytic leukemia, myelodysplastic syndrome  Evaluate safety and efficacy of atorvastatin for prophylaxis of GVHD in patients with hematologic malignances undergoing human leukocyte antigen–matched related donor HSCT
NCT01011478  National Surgical Adjuvant Breast and Bowel Project   Phase 3 Colorectal   Rosuvastatin vs placebo to prevent recurrence in patients with stage I or stage II surgically removed colon cancer
 NCT01772719  James Graham Brown Cancer Center  Interventional Refractory multiple myeloma   Effect of simvastatin with zoledronic acid on M-protein and/or free light chains when added to conventional chemotherapy
 NCT00572468  Department of Veterans Affairs  Interventional Prostate  Effect of simvastatin vs placebo on mevalonate pathway targets in men undergoing a prostatectomy as planned management for prostate cancer 

Note: All information found on

Abbreviations: NSCLC, non-small cell lung cancer; PK, pharmacokinetic; AML, acute myeloid leukemia; ALL, acute lymphoblastic leukemia; NHL, non-Hodgkin lymphoma; PSA, prostate-specific antigen; GVHD, graft-versus-host disease; DVT, deep vein thrombosis; HSCT,hematopoietic stem cell transplant.

Reducing Risk of Cancer Mortality: A New Role for Statins?

The Danish study did find, however, that “statin use in patients with cancer was associated with reduced cancer-related mortality.” These findings “are plausible,” the authors reported in the New England Journal of Medicine in 2012, because statins inhibit cholesterol synthesis within cells through the inhibition of HMG-CoA reductase, “the rate-limiting enzyme in the mevalonate and cholesterol-synthesis pathway.” 

They observed an association between the use of statins at the time of cancer diagnosis, with reduced cancer-related mortality among statin users versus those who had never used statins for each of the 13 types of cancer evaluated. Adjusted hazard ratios (HRs) were 0.85 (95% CI: 0.83- 0.87) for death from any cause and 0.85 (95% CI; 0.82- 0.87) for death from cancer. “Prospective evaluation of the hypothesis that statin use prolongs the survival of patients with cancer is needed,” they concluded.3

Dr. Nevadunsky, who is also an assistant professor in the Department of Obstetrics & Gynecology and Women's Health at the Albert Einstein College of Medicine of Yeshiva University, said their data on statins “suggest a survival advantage for women with endometrial cancer, and potential synergistic effect of aspirin use.”

As reported earlier on, a multivariate analysis showed that women who used statins had a 45% decreased hazard of death compared with nonhyperlipidemic women (HR, 0.55; 95% CI: 0.35-0.87). Further, aspirin users had improved survival compared with nonusers (HR, 0.47; 95% CI: 0.29-0.76). Women using statins and aspirin had an 84% decreased hazard of death compared with other groups (HR, 0.16; 95% CI: 0.07-0.38; P<0.01).4

The confounding effects of comorbidities such as cardiovascular disease “are extremely important in patients with endometrial cancer, as several metabolic issues, including diabetes and obesity, are risk factors for the development of endometrial cancer,” she added. To evaluate the contribution of cardiovascular disease to decreased mortality for women who are statin users, additional research needs to be conducted.

“Data from our preliminary retrospective analysis regarding decreased risk of mortality for women with endometrial cancer who were taking statin therapy is extremely compelling,” Dr. Nevadunsky said. “These data need to be further validated with prospective trials.” Further translational work is planned to elucidate the mechanism of action.

Abating Treatment Toxicities

Several ongoing phase 2 trials are assessing the effects of statins to abate toxicities of cancer treatments. Virginia Commonwealth University is conducting a phase 2 study of lovastatin in men with prostate cancer to determine if the agent protects against late effects of radiation therapy.  A randomized, controlled phase 2 trial in progress in New Zealand reported at ASCO is assessing the effect of simvastatin as prophylaxis against radiation-induced skin toxicity in patients with breast cancer.5 

Even in patients who were treated in childhood for acute lymphoblastic leukemia or non-Hodgkin lymphoma, the University of Minnesota Clinical and Translational Science Institute is evaluating the effects of 6 months of treatment with atorvastatin versus placebo on conduit artery endothelial function.

Abrogating Cancer's Effects

Three phase 2 studies are investigating whether atorvastatin can prevent GVHD in patients with hematologic malignancies undergoing myeloablative peripheral blood stem cell transplantation, allogeneic hematopoietic stem cell transplantation, and human leukocyte antigen–matched related donor HSCT.

Results of these and other studies, including the effects of statins on prostate-specific antigen and in combination with regimens (eg, FOLFIRI for colorectal cancer) will continue to delineate optimal patient populations for treatment with statins, and hopefully shed light on how and why statins are effective in these instances.


1. Demierre MF, Higgins PDR, Gruber SB, et al. Statins and cancer prevention. Nature. 2005;5:930-942.

2. Dale KM, Coleman CI, Henyan NN, Kluger J, White CM. Statins and cancer risk. A meta-analysis. JAMA. 2006;295:74-80.

3. Sune F, Nielsen SF, Nordestgaard BG, Bojesen SE. Statin use and reduced cancer-related mortality. N Engl J Med. 2012;367:1792-1802.

4. Spoozak LA, Girda E, Van Arsdale A, et al. Statin use in uterine malignancies. J Clin Oncol. 2013;31(suppl; abstr 5592).

5. Joseph H, Round G, Jameson MB, et al. Randomized controlled phase II trial of simvastatin as prophylaxis against radiation-induced skin toxicity in breast cancer patients. J Clin Oncol. 2013;31(suppl; abstr TPS1143).

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