How can non-aspirin NSAIDs help you? What the research says

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to reduce inflammation, with notable benefits in increasing survival and reducing risk of several types of cancer; however, expert consensus is that the risks of harm from using these drugs long-term are greater than the benefits for prevention against cancer for many people.

How can non-aspirin NSAIDs help you? What the research says

We summarize the clinical evidence for each medical benefit here. We begin with our assessment of the strength of evidence within each category, followed by a brief summary of individual studies or reviews of several studies. In assessing the strength of evidence, we consider the study design, number of participants, and the size of the treatment effect (how much outcomes changed with treatment).

To see more details, click the plus sign to the right of any section.

Our assessments of evidence for each medical benefit fall into one of these categories:

Strong evidence: consistent, significant effects in several large (or at least one very large) well designed clinical studies or at least two meta-analysesa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of clinical studies of moderate or better quality (or one large meta-analysis) finding similar results
Good evidence: significant effects in one large or several mid-sized and well-designed clinical studies ( randomized controlled trialsa study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects with an appropriate placebo or other strong comparison control or observational studies that control for confounds)
Modest evidence: significant effects in at least three small but well-designed randomized controlled trials (RCTs), or one or more well-designed, mid-sized clinical studies of reasonably good quality (RCTs or observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies), or several small studies aggregated into a meta-analysis
Preliminary evidence: significant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect
Weak evidence: one or more case studies, supported by animal evidence OR small treatment effects of limited clinical significance OR studies with no controls OR weak trends of effects
Insufficient evidence: preclinical evidence only OR clinical studies with such poor or unclear methodology that no conclusion can be drawn OR conflicting findings across clinical studies with no preponderance of evidence in one direction; conflicting evidence occurs when studies find conflicting effects (positive effect vs no effect or negative effect) with the same treatment and the same general study population (same cancer type, for example)

Learn more about how we research and rate therapies and practices in How We Rate Therapies ›

Preclinical evidencetesting a drug, a procedure, or another medical treatment in isolated cells or in animals; preclinical evidence is considered only an initial indication of possible effects in people is summarized in Are you a health professional? ›

COX inhibitors

You’ll see throughout this page mentions of COX-2 inhibitors and selective or non-selective COX inhibitors.

COX-2 (cyclooxygenase-2) is an enzyme responsible for inflammation and pain. COX-1 is a similar enzyme that also contributes to inflammation and pain, but in addition produces substances that activate platelets and protect the stomach and intestinal lining. COX-1 also helps maintain kidney blood flow and filtration.¹Ogbru A. COX-2 Inhibitor Medications. RX List. April 8, 2021. Viewed September 29, 2021. Any drugs that inhibit COX-1 also increase the risk of bleeding or problems with your stomach and kidneys.

COX-2 inhibitors were developed to target inflammation and pain, but with lower risk of bleeding, stomach, and kidney problems. NSAIDs that directly and selectively target COX-2 are classified as COX-2 selective inhibitors. Celecoxib is an example. Non-selective COX inhibitors, such as ibuprofen, inhibit both COX-1 and COX-2.²Dyall-Smith D. Non-steroidal anti-inflammatory drugs and their skin side effects. DermNet NZ. Viewed January 28, 2021.

Improving treatment outcomes

Are non-aspirin NSAIDs linked to improved survival? Are they linked to less cancer growth or metastasis? Do they enhance the anticancer action of other treatments or therapies? We present the evidence.

See preclinical evidencetesting a drug, a procedure, or another medical treatment in isolated cells or in animals; preclinical evidence is considered only an initial indication of possible effects in people of synergistic effects with conventionalthe cancer care offered by conventionally trained physicians and most hospitals; examples are chemotherapy, surgery, and radiotherapy and complementaryin cancer care, complementary care involves the use of therapies intended to enhance or add to standard conventional treatments; examples include supplements, mind-body approaches such as yoga or psychosocialtherapy, and acupuncture therapies in Are you a health professional? ›

Cancer as a whole

Preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of better survival among people with cancer-related malnutrition treated with indomethacin

No evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on survival among people with cancer treated with NSAIDs during treatment with immune checkpoint inhibitors

Breast cancer

No evidence of an effect among people with postmenopausal breast cancer treated with celecoxib, either alone or when combined with exemestane in 2 studies

Modest evidencesignificant effects in at least three small but well-designed randomized controlled trials (RCTs), or one or more well-designed, mid-sized clinical studies of reasonably good quality (RCTs or observational studies), or several small studies aggregated into a meta-analysis (this is the CancerChoices definition; other researchers and studies may define this differently) of better survival among people with breast cancer treated with ketorolac around the time of surgery

Celecoxib: no evidence of a effect on treatment among people with postmenopausal breast cancer treated with celecoxib, either alone or when combined with exemestane in 2 studies

No evidence of an effect on all-cause mortalitydeath, or the death rate in a population; cancer studies often report all-cause mortality (death from any cause) and cancer-specific mortality (death due to the cancer under investigation) or eventlocal/regional recurrence, distant metastasis, new primary cancer, or death from the cancer under investigation-free survival among people with postmenopausal hormone receptor-positive breast cancer treated with celecoxib for 18 months compared to placebo in a large RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects⁵Strasser-Weippl K, Higgins MJ et al. Effects of celecoxib and low-dose aspirin on outcomes in adjuvant aromatase inhibitor-treated patients: CCTG MA.27. Journal of the National Cancer Institute. 2018 Sep 1;110(9):1003-1008.
No evidence of an effect on proliferation or apoptosis among postmenopausal women with ER-positive ductal carcinoma in situ (DCIS) treated either with celecoxib alone or in combination with exemestane in a small RCT⁶Bundred NJ, Cramer A et al. Cyclooxygenase-2 inhibition does not improve the reduction in ductal carcinoma in situ proliferation with aromatase inhibitor therapy: results of the ERISAC randomized placebo-controlled trial. Clinical Cancer Research. 2010 Mar 1;16(5):1605-12.

Ketorolac: modest evidence of better survival among people with breast cancer treated with ketorolac around the time of surgery

Better overall survival among people undergoing conservative breast cancer surgery treated with ketorolac compared to no ketorolac in a mid-sized observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study⁷Forget P, Bentin C et al. Intraoperative use of ketorolac or diclofenac is associated with improved disease-free survival and overall survival in conservative breast cancer surgery. British Journal of Anaesthesia. 2014 Jul;113 Suppl 1:i82-7.
Better survival among people with early breast cancer treated with ketorolac around the time of surgery compared to no ketorolac in a mid-sized observational study⁸Forget P, Machiels JP et al. Neutrophil:lymphocyte ratio and intraoperative use of ketorolac or diclofenac are prognostic factors in different cohorts of patients undergoing breast, lung, and kidney cancer surgery. Annals of Surgical Oncology. 2013 Dec;20 Suppl 3:S650-60.

Colorectal cancer

Modest evidence of better survival among people with colorectal cancer with KRAS wild-type tumors, but not among those with KRAS-mutant tumors, treated with any NSAID

Weak evidence of better survival or of tumor response among people with colorectal cancer treated with celecoxib in addition to chemotherapy

Any NSAID: modest evidence of better survival among people with KRAS wild-type tumors, but not among those with KRAS-mutant tumors, treated with any NSAID

40% lower risk of overall mortality among people with colorectal cancer with KRAS wild-type tumors, but not among those with KRAS-mutant tumors, with use of any NSAID after diagnosis compared to no use in a large observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study⁹Hua X, Phipps AI et al. Timing of aspirin and other nonsteroidal anti-inflammatory drug use among patients with colorectal cancer in relation to tumor markers and survival. Journal of Clinical Oncology. 2017 Aug 20;35(24):2806-2813.

Celecoxib: weak evidence of better survival or of tumor response among people with colorectal cancer treated with celecoxib in addition to chemotherapy

A weak trend toward slightly better 5-year overall survival at either 3 or 5 years among people with stage 3 colon cancer treated with standard adjuvant fluorouracil, leucovorin, and oxaliplatin (FOLFOX) and 3 or more years of celecoxib (Celebrex) compared to FOLFOX alone in a very large RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹⁰Meyerhardt JA, Shi Q. Effect of celecoxib vs placebo added to standard adjuvant therapy on disease-free survival among patients with stage III colon cancer: the CALGB/SWOG 80702 (Alliance) randomized clinical trial. JAMA. 2021 Apr 6;325(13):1277-1286.
41% objective response rate among people with metastatic adenocarcinoma of the colon or rectum among people treated with a combination of intravenous irinotecan, oral capecitabine in 21-day cycles, and celecoxib at a daily dose of 800 mg for the duration of the study in a small uncontrolled triala study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design¹¹El-Rayes BF, Zalupski MM et al. Phase-II study of dose attenuated schedule of irinotecan, capecitabine, and celecoxib in advanced colorectal cancer. Cancer Chemotherapy and Pharmacology. 2008 Feb;61(2):283-9.
31.9% objective response rate among people with previously untreated metastatic colorectal cancer treated with weekly irinotecan, 5-fluorouracil, and leucovorin for 4 weeks every 6 weeks and oral celecoxib with in a small uncontrolled trial¹²Chen EY, Blanke CD et al. A phase II study of celecoxib with irinotecan, 5-fluorouracil, and leucovorin in patients with previously untreated advanced or metastatic colorectal cancer. American Journal of Clinical Oncology. 2018 Dec;41(12):1193-1198.

Gastrointestinal cancer

Colorectal cancer is listed separately.

Preliminary evidence of better survival among people with positive COX-2 expression and metastatic or postoperative recurrent stomach cancer treated with celecoxib in addition to chemotherapy

Head and neck cancer

Preliminary evidence of smaller tumor volume after diagnosis among people with head and neck cancer with PIK3CA gene mutations or amplification treated with sulindac or celecoxib

Kidney cancer

Preliminary evidence of better survival among people with kidney cancer treated with ketorolac around the time of surgery

Lung cancer

Preliminary (conflicting) evidence of better short-term survival—although good evidence of better response to chemotherapy—among people with advanced non-small cell lung cancer treated with celecoxib, but with serious toxicities

No evidence of improved survival among people with advanced non‐small cell lung cancer adding celecoxib to radiotherapy

Preliminary evidence of better survival among people with lung cancer treated with diclofenac around the time of surgery

Celecoxib: preliminary (conflicting) evidence of better short-term survival—although good evidence of better response to chemotherapy—among people with advanced non-small cell lung cancer treated with celecoxib, but with serious toxicities

Better response to first-line cancer treatment but no evidence of an effect on 5-year overall or progression-free survivalthe time during and after treatment of a disease that a patient lives without disease progression (worsening) among people with advanced non-small cell lung cancer treated with celecoxib compared to placebo in a meta-analysis meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 7 RCTsrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹⁶Yi L, Zhang W et al. Systematic review and meta-analysis of the benefit of celecoxib in treating advanced non-small-cell lung cancer. Drug Design, Development and Therapy. 2018 Aug 7;12:2455-2466.
Better overall response rate, but no evidence of an effect on 1-year survival, clinical benefit, complete response or partial response among people with advanced non‐small cell lung cancer treated with chemotherapy and celecoxib compared to chemotherapy alone, but with increased risk of the blood-related toxicities leukopeniaan abnormally low number of white cells in the blood, leading to increased susceptibility to infection or thrombocytopeniaan abnormally low number of platelets in the blood, which may cause easy bruising and excessive bleeding from wounds or bleeding in mucous membranes and other tissues in a meta-analysis of 6 RCTs¹⁷Hou LC, Huang F, Xu HB. Does celecoxib improve the efficacy of chemotherapy for advanced non-small cell lung cancer? British Journal of Clinical Pharmacology. 2016 Jan;81(1):23-32.
Better overall response rate, 12-month survival, and 6- and 12-month progression-free survival—but not 6-month survival—among people with advanced non‐small cell lung cancer treated with chemotherapy and celecoxib compared to chemotherapy alone, but with increased risk of toxicities (leukopenia, thrombocytopenia, cardiovascular events, and diarrhea) in meta-analyses of 8‒13 RCTs¹⁸Zhang W, Yi L et al. Comparison of the benefits of celecoxib combined with anticancer therapy in advanced non-small cell lung cancer: a meta-analysis. Journal of Cancer. 2020 Jan 20;11(7):1816-1827.
Better overall response rate and a weak trend toward better 12-month overall survival, plus better progression-free survival at 6 and 12 months, among people with advanced non‐small cell lung cancer treated with tyrosine kinase inhibitors and celecoxib compared to tyrosine kinase inhibitors alone in meta-analyses of 3‒5 RCTs¹⁹Zhang W, Yi L et al. Comparison of the benefits of celecoxib combined with anticancer therapy in advanced non-small cell lung cancer: a meta-analysis. Journal of Cancer. 2020 Jan 20;11(7):1816-1827.

With radiotherapy: no evidence of improved survival among people with advanced non‐small cell lung cancer adding celecoxib to radiotherapy

No evidence of an effect on 1-year overall survival among people with advanced non‐small cell lung cancer treated with radiotherapy and celecoxib compared to radiotherapy alone in a small RCT²⁰Zhang W, Yi L et al. Comparison of the benefits of celecoxib combined with anticancer therapy in advanced non-small cell lung cancer: a meta-analysis. Journal of Cancer. 2020 Jan 20;11(7):1816-1827.

Diclofenac: preliminary evidence of better survival among people with lung cancer treated with diclofenac around the time of surgery

Better survival among people with lung cancer treated with diclofenac use around the time of surgery compared to no diclofenac in a mid-sized observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study²¹Forget P, Machiels JP et al. Neutrophil:lymphocyte ratio and intraoperative use of ketorolac or diclofenac are prognostic factors in different cohorts of patients undergoing breast, lung, and kidney cancer surgery. Annals of Surgical Oncology. 2013 Dec;20 Suppl 3:S650-60.

Ovarian cancer

Modest evidence of lower cancer-specific mortalitydeath, or the death rate in a population; cancer studies often report all-cause mortality (death from any cause) and cancer-specific mortality (death due to the cancer under investigation) among people with epithelial ovarian cancer or serous ovarian cancer using non-aspirin NSAIDs after diagnosis

Weak evidence of a better response to carboplatin among heavily-treated people with recurrent ovarian cancer using celecoxib

No evidence of an effect on overall survival among people with ovarian cancer treated with metformin compared to no metformin in a meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies judged to be free of immortal time bias²²Majidi A, Na R, Dixon-Suen S, Jordan SJ, Webb PM. Common medications and survival in women with ovarian cancer: a systematic review and meta-analysis. Gynecological Oncology. 2020 Jun;157(3):678-685.
33% lower cancer-specific mortality among people with invasive, stage1–3 epithelial ovarian cancer with recent and regular non-aspirin NSAID use after diagnosis compared to never users, but no evidence of an effect of use before diagnosis in a large observational study²³Merritt MA, Rice MS et al. Pre-diagnosis and post-diagnosis use of common analgesics and ovarian cancer prognosis (NHS/NHSII): a cohort study. Lancet Oncology. 2018 Aug;19(8):1107-1116.
14–25% lower cancer-specific mortality among women with serous ovarian cancer but not other cancer subtypes with higher cumulative doses of non-aspirin NSAIDs after diagnosis compared to never users—but no evidence of an effect with infrequent users—in a large observational study;²⁴Verdoodt F, Dehlendorff C, Friis S, Kjaer SK. Non-aspirin NSAID use and ovarian cancer mortality. Gynecologic Oncology. 2018 Aug;150(2):331-337. also see evidence of higher mortality among people with non-serous ovarian tumors with NSAID use in Safety and precautions ›
Possibly increased sensitivity to carboplatin among heavily-treated people with recurrent ovarian cancer treated with celecoxib in a small uncontrolled triala study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design²⁵Legge F, Paglia A et al. Phase II study of the combination carboplatin plus celecoxib in heavily pre-treated recurrent ovarian cancer patients. BMC Cancer. 2011 May 31;11:214.

Sarcoma

Weak evidence of tumor response among people with Desmoid tumors (metronomic treatment) and inflammatory myofibroblastic tumors treated with diclofenac

NSAIDs combined with other therapies

Weak evidence of tumor response in a person with inoperable pancreatic cancer with a combination treatment of gemcitabine plus diclofenac, cimetidine, low-dose cyclophosphamide, and sulfasalazine

Optimizing your body terrain

Do non-aspirin NSAIDs promote an environment within your body that is less supportive of cancer development, growth, or spread? We present the evidence.

See Optimizing Your Body Terrain ›

Find medical professionals who specialize in managing body terrain factors: Finding Integrative Oncologists and Other Practitioners ›

We also recommend that you share with your doctor the information here about how non-aspirin NSAIDs might affect these terrain factors if you have any imbalances.

Blood sugar and insulin resistance

Weak evidenceone or more case studies, supported by animal evidence OR small treatment effects of limited clinical significance OR studies with no controls OR weak trends of effects (this is the CancerChoices definition; other researchers and studies may define this differently) of lower fasting blood sugar among people with type 2 diabetes treated with usual oral hypoglycemic therapy and ibuprofen

Inflammation

NSAIDS—non-steroidal anti-inflammatory drugs—are widely recognized as having strong anti-inflammatory effects. Small studies provide preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of this effect among people with advanced cancer.

NSAIDs combined with other therapies

Celecoxib with a special diet, supplements, and medroxyprogesterone acetate: weak evidence of less inflammation among people with cancer-related anorexia/cachexia and oxidative stress treated with a special diet, antioxidants, medroxyprogesterone acetate, and celecoxib

Managing side effects and promoting wellness

Are non-aspirin NSAIDs linked to fewer or less severe side effects or symptoms? Are they linked to less toxicity from cancer treatment? Do they support your quality of life or promote general well-being? We present the evidence.

Side effects as a whole

No evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on the toxicity of exemestane among postmenopausal women with advanced hormone-sensitive breast cancer treated with celecoxib in a preliminary trial

Anxiety

No evidence of an effect on anxiety during chemotherapy among people with stomach cancer treated with celecoxib in a preliminary study

Blood-related symptoms

No evidence of an effect on neutropenia during chemotherapy among people with stomach cancer treated with celecoxib in a preliminary study

Body composition or cachexia

No evidence of an effect on chemotherapy-induced wasting (cachexia) among people with stomach cancer treated with celecoxib in a preliminary study

Preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of better body weight among people with several types of cancer, including advanced cancer, treated with celecoxib

Preliminary evidence of weight gain among people with advanced metastatic gastrointestinal cancer treated with ibuprofen

Preliminary evidence of better resting energy expenditure and weight gain among people with cancer treated with indomethacin

Celecoxib (Celebrex):

No evidence of an effect on chemotherapy-induced wasting (cachexia) among people with stomach cancer treated with celecoxib in a preliminary study

Preliminary evidence of better body weight among people with several types of cancer, including advanced cancer, treated with celecoxib

Preliminary evidence of less loss of bone mineral density during exemestane treatment among people with hormone-sensitive breast cancer treated with celecoxib

Cachexia: no evidence of an effect on chemotherapy-induced wasting (cachexia) among people with stomach cancer treated with celecoxib in a preliminary study

No evidence of an effect on cachexia among people with metastatic or postoperative recurrent stomach (gastric) cancer treated with chemotherapy with celecoxib compared to chemotherapy alone in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects³⁶Guo Q, Li Q et al. A comprehensive evaluation of clinical efficacy and safety of celecoxib in combination with chemotherapy in metastatic or postoperative recurrent gastric cancer patients: a preliminary, three-center, clinical trial study. Medicine (Baltimore). 2019 Jul;98(27):e16234.

Body weight: preliminary evidence of better body weight among people with several types of cancer, including advanced cancer, treated with celecoxib

Better body weight among people with advanced and progressive lung cancer treated with fish oil supplementation and celecoxib compared to fish oil and placebo in a small RCT³⁷Cerchietti LC, Navigante AH, Castro MA. Effects of eicosapentaenoic and docosahexaenoic n-3 fatty acids from fish oil and preferential Cox-2 inhibition on systemic syndromes in patients with advanced lung cancer. Nutrition and Cancer. 2007;59(1):14-20.
Gain in body weight and body mass index (BMI) while awaiting cancer treatment among people with gastrointestinal or head and neck cancer treated with celecoxib compared to weight loss with placebo in a small RCT³⁸Lai V, George J et al. Results of a pilot study of the effects of celecoxib on cancer cachexia in patients with cancer of the head, neck, and gastrointestinal tract. Head & Neck. 2008 Jan;30(1):67-74.

Ibuprofen: preliminary evidence of weight gain among people with advanced metastatic gastrointestinal cancer treated with ibuprofen

Weight gain among people with advanced metastatic gastrointestinal cancer experiencing more than 5% weight loss treated with megestrol acetate (MA) plus ibuprofen compared to weight loss with MA plus placebo in a small RCT³⁹McMillan DC, Wigmore SJ et al. A prospective randomized study of megestrol acetate and ibuprofen in gastrointestinal cancer patients with weight loss. British Journal of Cancer. 1999 Feb;79(3-4):495-500.

Indomethacin: preliminary evidence of better resting energy expenditure and weight gain among people with cancer treated with indomethacin

Less of an increase in resting energy expenditure among people with cancer who had been losing weight treated with long-term indomethacin compared to undernourished people without cancer in an observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study⁴⁰Lundholm K, Daneryd P, Körner U, Hyltander A, Bosaeus I. Evidence that long-term COX-treatment improves energy homeostasis and body composition in cancer patients with progressive cachexia. International Journal of Oncology. 2004 Mar;24(3):505-12.
Increased body weight preserving body fat but not significantly improving lean body mass among people with cancer who had been losing weight treated with long-term indomethacin with an unclear comparison group (implied no indomethacin) in an observational study⁴¹Lundholm K, Daneryd P, Körner U, Hyltander A, Bosaeus I. Evidence that long-term COX-treatment improves energy homeostasis and body composition in cancer patients with progressive cachexia. International Journal of Oncology. 2004 Mar;24(3):505-12.

Bone and joint symptoms

Preliminary evidence of less loss of bone mineral density during exemestane treatment among people with hormone-sensitive breast cancer treated with celecoxib

Changes in appetite

No evidence of an effect on chemotherapy-induced loss of appetite among people with stomach cancer treated with celecoxib in a preliminary study

Preliminary evidence of improved appetite among people with advanced metastatic gastrointestinal cancer treated with ibuprofen

Fatigue

No evidence of an effect on fatigue during chemotherapy among people with stomach cancer treated with celecoxib in a preliminary study

Gastrointestinal symptoms, including nausea and vomiting

No evidence of an effect on chemotherapy-induced vomiting or diarrhea among people with stomach cancer treated with celecoxib in a preliminary study

Neurological symptoms

No evidence of an effect on chemotherapy-induced peripheral neurotoxicity among people with stomach cancer treated with celecoxib in a preliminary study

Oral symptoms

No evidence of an effect on chemotherapy-induced dry mouth among people treated with celecoxib in a preliminary study

Pain

Good evidencesignificant effects in one large or several mid-sized and well-designed clinical studies (randomized controlled trials (RCTs) with an appropriate placebo or other strong comparison control or observational studies that control for confounds) (this is the CancerChoices definition; other researchers and studies may define this differently) of less persistent cancer pain among people treated with diclofenac

No evidence of an effect on intensity of persistent cancer pain among people treated with ibuprofen, ketorolac tromethamine, naproxen, or sulindac in a large combined review of studies

Preliminary evidence of less pain among people with cancer-related malnutrition treated with indomethacin

The main use of NSAIDs is to reduce fever and inflammation, which is often accompanied by pain.⁴⁹Nonsteroidal Anti-inflammatory Drugs (NSAIDs). US Food and Drug Administration. December 9, 2020. Viewed February 9, 2021. Because NSAIDs are so effective in reducing pain from inflammation, they are some of the most commonly used medications.⁵⁰Bindu S, Mazumder S, Bandyopadhyay U. Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: a current perspective. Biochemical Pharmacology. 2020 Oct;180:114147. We present findings specific to cancer pain. Also see evidence of worse pain scores among people with metastatic or postoperative recurrent stomach (gastric) cancer treated with chemotherapy with celecoxib in Safety and precautions ›

Diclofenac: good evidence of less persistent cancer pain among people treated with diclofenac

Less persistent (chronic) cancer pain among people treated with diclofenac compared to placebo in a large meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 18 RCTsrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects⁵¹Huang R, Jiang L et al. Comparative efficacy of therapeutics for chronic cancer pain: a Bayesian network meta-analysis. Journal of Clinical Oncology. 2019 Jul 10;37(20):1742-1752.
Diclofenac “has an established role in oncological practice in the treatment of cancer-related pain.”⁵²Pantziarka P, Sukhatme V, Bouche G, Meheus L, Sukhatme VP. Repurposing Drugs in Oncology (ReDO)-diclofenac as an anti-cancer agent. Ecancermedicalscience. 2016;10:610.

Ibuprofen: no evidence of an effect on persistent cancer pain intensity among people treated with ibuprofen in a large combined review of studies

No evidence of an effect on persistent (chronic) cancer pain intensity among people treated with ibuprofen compared to placebo in a large meta-analysis of 18 RCTs⁵³Huang R, Jiang L et al. Comparative efficacy of therapeutics for chronic cancer pain: a Bayesian network meta-analysis. Journal of Clinical Oncology. 2019 Jul 10;37(20):1742-1752.

Indomethacin

Preliminary evidence of less pain among people with cancer-related malnutrition treated with indomethacin, but see evidence of worse persistent cancer pain in Safety and precautions ›

Less pain and less analgesic use among people with insidious or overt malnutrition due to generalized malignancy treated with indomethacin in a mid-sized RCT⁵⁴Lundholm K, Gelin J et al. Anti-inflammatory treatment may prolong survival in undernourished patients with metastatic solid tumors. Cancer Research. 1994 Nov 1;54(21):5602-6.

Ketorolac tromethamine: no evidence of an effect on persistent cancer pain intensity among people treated with ketorolac tromethamine in a large combined review of studies

No evidence of an effect on persistent (chronic) cancer pain intensity among people treated with ketorolac tromethamine compared to placebo in a large meta-analysis of 18 RCTs⁵⁵Huang R, Jiang L et al. Comparative efficacy of therapeutics for chronic cancer pain: a Bayesian network meta-analysis. Journal of Clinical Oncology. 2019 Jul 10;37(20):1742-1752.

Naproxen: no evidence of an effect on persistent cancer pain intensity among people treated with naproxen in a large combined review of studies

No evidence of an effect on persistent (chronic) cancer pain intensity among people treated with naproxen compared to placebo in a large meta-analysis of 18 RCTs⁵⁶Huang R, Jiang L et al. Comparative efficacy of therapeutics for chronic cancer pain: a Bayesian network meta-analysis. Journal of Clinical Oncology. 2019 Jul 10;37(20):1742-1752.

Sulindac: no evidence of an effect on intensity of persistent cancer pain among people treated with sulindac in a large combined review of studies

No evidence of an effect on persistent (chronic) cancer pain intensity among people treated with sulindac compared to placebo in a large meta-analysis of 18 RCTs⁵⁷Huang R, Jiang L et al. Comparative efficacy of therapeutics for chronic cancer pain: a Bayesian network meta-analysis. Journal of Clinical Oncology. 2019 Jul 10;37(20):1742-1752.

Quality of life and physical function

Celecoxib

Preliminary evidence of better quality of life among people with stomach cancer treated with celecoxib

Preliminary evidence of better strength among people with lung cancer treated with celecoxib

Preliminary evidence of better function during exemestane treatment among women with breast cancer treated with celecoxib

Indomethacin: preliminary evidence of better physical function among people with cancer-related malnutrition

Ibuprofen: preliminary evidence of better quality of life among people with advanced metastatic gastrointestinal cancer

NSAIDs combined with other therapies

Preliminary evidence of less fatigue and better global quality of life among people with advanced gynecological cancer treated with celecoxib, carnitine, and antioxidants

Weak evidenceone or more case studies, supported by animal evidence OR small treatment effects of limited clinical significance OR studies with no controls OR weak trends of effects (this is the CancerChoices definition; other researchers and studies may define this differently) of better appetite, body weight and lean body mass, less fatigue, and better quality of life among people with cancer-related anorexia/cachexia and oxidative stress treated with a diet rich in polyphenols, antioxidants, medroxyprogesterone acetate, and celecoxib

Celecoxib, carnitine, and antioxidants: preliminary evidence of less fatigue and better global quality of life among people with advanced gynecological cancer treated with celecoxib, carnitine, and antioxidants

Less fatigue, increased lean body mass, better resting energy expenditure, and better global quality of life among women with advanced gynecological cancer treated with megestrol acetate (MA), celecoxib, carnitine, and antioxidants compared to MA alone in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects⁶⁴Macciò A, Madeddu C et al. A randomized phase III clinical trial of a combined treatment for cachexia in patients with gynecological cancers: evaluating the impact on metabolic and inflammatory profiles and quality of life. Gynecologic Oncology. 2012 Mar;124(3):417-25.

Celecoxib with a special diet, supplements, and medroxyprogesterone acetate: weak evidence of better appetite, body weight and lean body mass; less fatigue; and better quality of life among people with cancer-related anorexia/cachexia and oxidative stress treated with a diet rich in polyphenols, antioxidants, medroxyprogesterone acetate, and celecoxib

Better appetite, body weight and lean body mass; less fatigue; and better quality of life among people with cancer-related anorexia/cachexia and oxidative stress treated with a diet rich in polyphenols, antioxidants (alpha-lipoic acid, carbocysteine lysine salt, vitamin E, A and C), and pharmaconutritional support enriched with omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid), medroxyprogesterone acetate, and celecoxib for 4 months compared to baseline in a small uncontrolled triala study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design⁶⁵Mantovani G, Macciò A et al. A phase II study with antioxidants, both in the diet and supplemented, pharmaconutritional support, progestagen, and anti-cyclooxygenase-2 showing efficacy and safety in patients with cancer-related anorexia/cachexia and oxidative stress. Cancer Epidemiology, Biomarkers & Prevention. 2006;15(5):1030-1034.

Reducing cancer risk

Are non-aspirin NSAIDs linked to lower risks of developing cancer or of recurrence? We present the evidence.

Breast cancer

Celecoxib: no evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on recurrence (disease-free survivalthe time during and after successful treatment of a disease during which there are no signs and symptoms of the disease that was treated; this is the same as recurrence-free survival) among people with postmenopausal hormone receptor-positive breast cancer treated with celecoxib

Ibuprofen: preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of lower risk of breast cancer recurrence among people currently using ibuprofen at least 3 days per week

Modest evidencesignificant effects in at least three small but well-designed randomized controlled trials (RCTs), or one or more well-designed, mid-sized clinical studies of reasonably good quality (RCTs or observational studies), or several small studies aggregated into a meta-analysis (this is the CancerChoices definition; other researchers and studies may define this differently) of lower risk of recurrence among people using ketorolac at the time of breast cancer surgery

Insufficient (conflicting) evidencepreclinical evidence only OR clinical studies with such poor or unclear methodology that no conclusion can be drawn OR conflicting findings across clinical studies with no preponderance of evidence in one direction; conflicting evidence occurs when studies find conflicting effects (positive effect vs no effect or negative effect) with the same treatment and the same general study population (same cancer type, for example) (this is the CancerChoices definition; other researchers and studies may define this differently) of an effect on breast cancer risk among people using non-aspirin NSAIDs

Modest evidence of lower risk of breast cancer with ibuprofen use

Recurrence

Celecoxib: no evidence of an effect on recurrence (disease-free survival) among people with postmenopausal hormone receptor-positive breast cancer treated with celecoxib

No evidence of an effect on recurrence among people with postmenopausal hormone receptor-positive breast cancer treated with celecoxib for 18 months compared to placebo in a large RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects⁶⁶Strasser-Weippl K, Higgins MJ et al. Effects of celecoxib and low-dose aspirin on outcomes in adjuvant aromatase inhibitor-treated patients: CCTG MA.27. Journal of the National Cancer Institute. 2018 Sep 1;110(9):1003-1008.

Ibuprofen: Preliminary evidence of lower risk of breast cancer recurrence among people currently using ibuprofen at least 3 days per week

Lower risk of breast cancer recurrence among people currently use ibuprofen at least 3 days per week compared to no use in a mid-sized observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study⁶⁷Kwan ML, Habel LA, Slattery ML, Caan B. NSAIDs and breast cancer recurrence in a prospective cohort study. Cancer Causes and Control. 2007 Aug;18(6):613-20.

Ketorolac: modest evidence of lower risk of recurrence among people using ketorolac at the time of breast cancer surgery

Lower risk of recurrence among people with invasive breast cancer, especially among people with high body mass index (BMI), with a single dose of ketorolac at the time of primary tumor surgery compared to no ketorolac in a large observational study, but no evidence of an effect with diclofenac⁶⁸Desmedt C, Demicheli R et al. Potential benefit of intra-operative administration of ketorolac on breast cancer recurrence according to the patient’s body mass index. Journal of the National Cancer Institute. 2018 Oct 1;110(10):1115-1122.
Lower risk of recurrence (better disease-free survival) in the first few years after mastectomy with ketorolac use around the time of surgery compared to no ketorolac in a mid-sized observational study⁶⁹Retsky M, Demicheli R et al. Reduction of breast cancer relapses with perioperative non-steroidal anti-inflammatory drugs: new findings and a review. Current Medicinal Chemistry. 2013;20(33):4163-76.
Lower risk of recurrence (better disease-free survival) among people undergoing conservative breast cancer surgery with ketorolac compared to no ketorolac in a mid-sized observational study⁷⁰Forget P, Bentin C et al. Intraoperative use of ketorolac or diclofenac is associated with improved disease-free survival and overall survival in conservative breast cancer surgery. British Journal of Anaesthesia. 2014 Jul;113 Suppl 1:i82-7.
Lower rate of recurrence among women undergoing mastectomy with axillary dissection for breast cancer with ketorolac use just before surgery compared to no ketorolac in a mid-sized observational study⁷¹Forget P, Vandenhende J et al. Do intraoperative analgesics influence breast cancer recurrence after mastectomy? A retrospective analysis. Anesthesia & Analgesia. 2010 Jun 1;110(6):1630-5.

Cancer diagnosis

Non-aspirin NSAIDs as a whole: insufficient (conflicting) evidence of an effect on breast cancer risk among people using non-aspirin NSAIDs; the conflict may be due to different responses across different populations

No evidence of an effect on breast cancer incidence, either overall or by estrogen receptor or progesterone receptor status, among people using non-aspirin NSAIDs compared to no use in a very large observational study⁷²Bardia A, Olson JE et al. Effect of aspirin and other NSAIDs on postmenopausal breast cancer incidence by hormone receptor status: results from a prospective cohort study. Breast Cancer Research and Treatment. 2011 Feb;126(1):149-55.
No evidence of an effect on risk of breast cancer among people with past or current use of non-aspirin NSAIDs, regardless of dose, frequency, or duration of use, either for overall breast cancer or by ER/PR status, compared to no use in a very large observational study⁷³Zhang X, Smith-Warner SA et al. Use of aspirin, other nonsteroidal anti-inflammatory drugs, and acetaminophen and postmenopausal breast cancer incidence. Journal of Clinical Oncology. 2012 Oct 1;30(28):3468-77.
No evidence of an effect on risk of breast cancer among people using non-selective NSAIDs, regardless of intensity or duration of use, compared to no use in a very large observational study⁷⁴Cronin-Fenton DP, Pedersen L et al. Prescriptions for selective cyclooxygenase-2 inhibitors, non-selective non-steroidal anti-inflammatory drugs, and risk of breast cancer in a population-based case-control study. Breast Cancer Res. 2010;12(2):R15.
30% lower risk of breast cancer with current use of non-aspirin NSAIDs for 6 or more years, but not with past use (compared to no use), with the lower risk limited to Caucasians, Americans of African descent, and women with at least 1 positive hormone receptor in a very large observational study⁷⁵Gill JK, Maskarinec G et al. Nonsteroidal antiinflammatory drugs and breast cancer risk: the multiethnic cohort. American Journal of Epidemiology. 2007 Nov 15;166(10):1150-8.

Ibuprofen: modest evidence of lower risk of breast cancer with ibuprofen use; see also higher risk of some types of breast cancer among people using ibuprofen in Safety and precautions ›

55% lower risk of breast cancer among people using ibuprofen compared to no use in a pooled analysis of observational studies⁷⁶Harris RE, Beebe J, Alshafie GA. Reduction in cancer risk by selective and nonselective cyclooxygenase-2 (COX-2) inhibitors. Journal of Experimental Pharmacology. 2012 Aug 10;4:91-6.

Colorectal cancer

Good evidencesignificant effects in one large or several mid-sized and well-designed clinical studies (randomized controlled trials (RCTs) with an appropriate placebo or other strong comparison control or observational studies that control for confounds) (this is the CancerChoices definition; other researchers and studies may define this differently) of lower risk of colorectal cancer among people using NSAIDs as a whole

Preliminary evidence of lower colorectal cancer risk among people using COX-2 inhibitors

Good evidence of lower risk of adenomas and advanced adenomas among people using celecoxib

Preliminary evidence of substantially lower risk of colon cancer among people using ibuprofen

Modest evidence of fewer adenomas, polyps, and aberrant crypt foci among people with or without familial adenomatous polyposis treated with sulindac

Recurrence

Weak evidence of lower risk of recurrence among people using celecoxib

A weak trendan apparent change due to a therapy, close to but not achieving full statistical significance (this is the CancerChoices definition; other researchers and studies may define this differently toward slightly lower disease recurrence among people with stage 3 colon cancer with 3 years of celecoxib (Celebrex) added to standard adjuvant fluorouracil, leucovorin, and oxaliplatin (FOLFOX) compared to FOLFOX alone in a very large RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects⁷⁷Meyerhardt JA, Shi Q. Effect of celecoxib vs placebo added to standard adjuvant therapy on disease-free survival among patients with stage III colon cancer: the CALGB/SWOG 80702 (Alliance) randomized clinical trial. JAMA. 2021 Apr 6;325(13):1277-1286.

Colorectal cancer risk

Good evidence of lower risk of colorectal cancer among people using NSAIDs as a whole

Preliminary evidence of lower colorectal cancer risk among people using COX-2 inhibitors

Good evidence of lower risk of adenomas and advanced adenomas among people using celecoxib

Preliminary evidence of substantially lower risk of colon cancer among people using ibuprofen

Modest evidence of fewer adenomas, polyps, and aberrant crypt foci among people with or without familial adenomatous polyposis treated with sulindac

NSAIDs as a whole: good evidence of lower risk of colorectal cancer among people using NSAIDs

Lower risk of colorectal cancer among people aged 40 or older with non-aspirin NSAID use compared to no use, especially for women (19% lower risk), higher doses (18% lower risk), distal colon cancer (22% lower risk) and white people (31–41% lower risk) in a very large meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 23 observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies⁷⁸Tomić T, Domínguez-López S, Barrios-Rodríguez R. Non-aspirin non-steroidal anti-inflammatory drugs in prevention of colorectal cancer in people aged 40 or older: a systematic review and meta-analysis. Cancer Epidemiology. 2019;58:52–62.
Lower risk of colorectal cancer at 3 years after a negative baseline colonoscopy, but not at longer follow up, among people taking non-aspirin NSAIDs before colonoscopy compared to no NSAIDs in a very large observational study⁷⁹Cheung KS, Chen L, Chan EW, Seto WK, Wong ICK, Leung WK. Nonsteroidal anti-inflammatory drugs but not aspirin are associated with a lower risk of post-colonoscopy colorectal cancer. Alimentary Pharmacology & Therapeutics. 2020;51:899–908.
35% lower risk of proximal and 31% lower risk of distal colon cancer, but no evidence of an effect on rectal cancer among people using non-aspirin NSAIDs daily compared to non-users in a very large observational study⁸⁰Ruder EH, Laiyemo AO et al. Non-steroidal anti-inflammatory drugs and colorectal cancer risk in a large, prospective cohort. American Journal of Gastroenterology. 2011 Jul;106(7):1340-50.
Substantially lower risk of colorectal cancer among people using non-aspirin NSAIDs, particularly long-term, high-intensity use of selective COX-2 inhibitors compared to no use in a very large observational study⁸¹Friis S, Riis AH, Erichsen R, Baron JA, Sørensen HT. Low-dose aspirin or nonsteroidal anti-inflammatory drug use and colorectal cancer risk: a population-based, case-control study. Annals of Internal Medicine. 2015 Sep 1;163(5):347-55.
Lower risk of colon cancer among people using selective COX-2 inhibitors, ibuprofen, or naproxen compared to no use in a mid-sized observational study⁸²Harris RE, Beebe-Donk J, Alshafie GA. Similar reductions in the risk of human colon cancer by selective and nonselective cyclooxygenase-2 (COX-2) inhibitors. BMC Cancer. 2008 Aug 14;8:237.
Lower risk of adenomatous polyps among people using non-aspirin NSAIDs compared to no use in a large observational study⁸³Murff HJ, Shrubsole MJ et al. Nonsteroidal anti-inflammatory drug use and risk of adenomatous and hyperplastic polyps. Cancer Prevention Research (Phila). 2011 Nov;4(11):1799-807.

Selective cyclooxygenase-2 (COX-2) inhibitors as a whole: preliminary evidence of lower colorectal cancer risk among people using COX-2 inhibitors

70% lower risk of colon cancer among people using selective cyclooxygenase-2 (COX-2) inhibitors compared to no use in a mid-sized observational study⁸⁴Harris RE, Beebe J, Alshafie GA. Reduction in cancer risk by selective and nonselective cyclooxygenase-2 (COX-2) inhibitors. Journal of Experimental Pharmacology. 2012 Aug 10;4:91-6.

Celecoxib (Celebrex): strong evidence of lower risk of adenomas and advanced adenomas among people using celecoxib

Lower risk of recurrent adenomas (34% lower risk) and advanced adenomas (55% lower risk) over a 3-year follow-up among people using celecoxib 400 mg/day compared to controls, and an increased risk 2 years after celecoxib use was stopped, in a meta-analysis of 5 RCTs⁸⁵Veettil SK, Lim KG et al. Effects of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs on the incidence of recurrent colorectal adenomas: a systematic review with meta-analysis and trial sequential analysis of randomized clinical trials. BMC Cancer. 2017 Nov 14;17(1):763.
Somewhat fewer adenomas and moderately fewer advanced adenomas over 5 years among people at high risk for colorectal cancer taking either low or high doses of celecoxib for 3.1 years (discontinued due to safety concerns) in a very large RCT⁸⁶Bertagnolli MM, Eagle CJ et al; Adenoma Prevention with Celecoxib Study Investigators. Five-year efficacy and safety analysis of the Adenoma Prevention with Celecoxib Trial. Cancer Prevention Research (Phila). 2009 Apr;2(4):310-21.
36% lower rate of adenomas and 51% lower rate of advanced adenomas after 3 years among people who had had adenomas removed before enrollment taking 400 mg celecoxib daily compared to placebo in a very large RCT⁸⁷Arber N, Eagle CJ et al; PreSAP Trial Investigators. Celecoxib for the prevention of colorectal adenomatous polyps. New Engand Journal of Medicine. 2006 Aug 31;355(9):885-95.
Fewer adenomas at 1 and 3 years among people who had adenomas removed before study entry taking 200 mg celecoxib or 400 mg celecoxib twice a day compared to placebo, with the greatest effects among people whose pretreatment adenomas demonstrated elevated COX-2 or 15-PGDH loss in a very large RCT⁸⁸Wang J, Cho NL et al. Chemopreventive efficacy of the cyclooxygenase-2 (Cox-2) inhibitor, celecoxib, is predicted by adenoma expression of Cox-2 and 15-PGDH. Cancer Epidemiology, Biomarkers & Prevention. 2018 Jul;27(7):728-736.

Ibuprofen: preliminary evidence of substantially lower risk of colon cancer among people using ibuprofen

72% lower risk of colon cancer among people using ibuprofen compared to no use in a mid-sized observational study⁸⁹Harris RE, Beebe J, Alshafie GA. Reduction in cancer risk by selective and nonselective cyclooxygenase-2 (COX-2) inhibitors. Journal of Experimental Pharmacology. 2012 Aug 10;4:91-6.

Sulindac: modest evidence of fewer adenomas, polyps, and aberrant crypt foci among people with or without familial adenomatous polyposis treated with sulindac

Fewer aberrant crypt foci after 2 months, and fewer adenomas and a weak trend toward fewer total polyps at 12 months, among people without polyps or who had undergone polypectomy treated with sulindac 300 mg daily compared to placebo, and more benefit among those who had undergone polypectomy in a mid-sized RCT⁹⁰Takayama T, Nagashima H et al. Randomized double-blind trial of sulindac and etodolac to eradicate aberrant crypt foci and to prevent sporadic colorectal polyps. Clinical Cancer Research. 2011 Jun 1;17(11):3803-11.
Fewer recurrences of adenomas among people with a history of resected adenomas treated with 500 mg difluoromethylornithine (DFMO) and 150 mg sulindac daily compared to placebos, without a significant increase in adverse events in a mid-sized RCT⁹¹Meyskens FL Jr, McLaren CE et al. Difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas: a randomized placebo-controlled, double-blind trial. Cancer Prevention Research (Philadelphia). 2008 Jun;1(1):32-8.
Substantially fewer and smaller polyps among people with familial adenomatous polyposis, the majority of whom had not undergone colectomy, treated with sulindac 150 mg orally twice a day for 9 months compared to placebo in a small RCT⁹²Giardiello FM, Hamilton SR et al. Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. New England Journal of Medicine. 1993 May 6;328(18):1313-6.
No evidence of an effect on the development of adenomas among people aged 8 to 25 who were genotypically affected with familial adenomatous polyposis but had not shown development of polyps treated with sulindac either 75 or 150 mg orally twice a day for 4 years in a small RCT⁹³Giardiello FM, Yang VW et al. Primary chemoprevention of familial adenomatous polyposis with sulindac. New England Journal of Medicine. 2002 Apr 4;346(14):1054-9.

Gastrointestinal cancer

Colorectal cancer is listed separately.

No evidence of a lower risk of bile duct cancer (cholangiocarcinoma) among people using non-aspirin NSAIDs in a very large combined analysis of studies

Head and neck cancer

Weak evidence of lower risk of head and neck cancer among people treated with NSAIDs

Lung cancer

Modest evidence of lower risk of lung cancer among people using ibuprofen or selective COX-2 inhibitors such as celecoxib

Melanoma and other skin cancer

Good evidencesignificant effects in one large or several mid-sized and well-designed clinical studies (randomized controlled trials (RCTs) with an appropriate placebo or other strong comparison control or observational studies that control for confounds) (this is the CancerChoices definition; other researchers and studies may define this differently) of lower risk of squamous cell carcinoma and malignant melanoma among people using NSAIDs

Prostate cancer

Preliminary (conflicting) evidence of lower risk of prostate cancer among people using ibuprofen or non-aspirin NSAIDs as a whole

Keep reading about non-aspirin NSAIDs

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Nancy Hepp, MS

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Laura Pole, MSN, RN, OCNS

Senior Clinical Consultant

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Barry D. Elson, MD

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Research Associate

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Last update: December 19, 2023

Last full literature review: September 2021

CancerChoices provides information about integrative in cancer care, a patient-centered approach combining the best of conventional care, self care and evidence-informed complementary care in an integrated plan cancer care. We review complementaryin cancer care, complementary care involves the use of therapies intended to enhance or add to standard conventional treatments; examples include supplements, mind-body approaches such as yoga or psychosocial therapy, and acupuncture therapies and self-care lifestyle actions and behaviors that may impact cancer outcomes; examples include eating health-promoting foods, limiting alcohol, increasing physical activity, and managing stress practices to help patients and professionals explore and integrate the best combination of conventionalthe cancer care offered by conventionally trained physicians and most hospitals; examples are chemotherapy, surgery, and radiotherapy and complementary therapies and practices for each person.

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Non-aspirin Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

How can non-aspirin NSAIDs help you? What the research says

COX inhibitors

Improving treatment outcomes

Optimizing your body terrain

Managing side effects and promoting wellness

Reducing cancer risk

Keep reading about non-aspirin NSAIDs

Author

Nancy Hepp, MS

Reviewers

Laura Pole, MSN, RN, OCNS

Barry D. Elson, MD

Andrew Jackson, ND

Learn more

Aspirin

Self Care

Integrative Medicine at NCI Cancer Centers

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