How can cimetidine and other H2 blockers help you? What the research says

H2 blockers, used to treat gastrointestinal ulcers and/or reduce stomach acid, may improve survival among people with cancer, especially after colorectal cancer resection.

How can H2 blockers 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 ›

Improving treatment outcomes

Are cimetidine and other H2 blockers 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.

Advanced cancer

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 a clinical response among people with advanced renal cell carcinoma treated with cimetidine

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 tumor response or survival among people with metastatic malignant melanoma treated with cimetidine, sometimes in addition to conventional treatments

Preliminary evidence of better prognosis and overall survival after primary surgery among people with advanced serous ovarian carcinoma treated with platinum-based systemic chemotherapy and cimetidine

Advanced cancer as a whole: preliminary evidence of longer survival and a large rise in performance status among people with advanced cancer treated with a daily combination of subcutaneous histamine and oral H2-antihistaminics

Considerably longer survival and a large rise in performance status among people with advanced cancer for whom classical anticancer therapy had been abandoned treated with a daily combination of subcutaneous histamine and oral H2-antihistaminics compared to untreated controls in a small 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 effects¹Burtin C, Noirot C et al. Clinical improvement in advanced cancer disease after treatment combining histamine and H2-antihistaminics (ranitidine or cimetidine). European Journal of Cancer & Clinical Oncology. 1988 Feb;24(2):161-7.

Advanced kidney cancer: weak evidence of a clinical response among people with advanced renal cell carcinoma treated with cimetidine

A very 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 better clinical response among people with advanced renal cell carcinoma treated with natural interferon-α plus daily oral cimetidine compared to interferon-α alone in a small RCT²Kinouchi T, Sakamoto J et al; Immunotherapy Oncology Group for Renal Cell Carcinoma. Prospective randomized trial of natural interferon-alpha versus natural interferon-alpha plus cimetidine in advanced renal cell carcinoma with pulmonary metastasis. Journal of Cancer Research and Clinical Oncology. 2006 Aug;132(8):499-504.
2 complete remissions and no partial remissions among 38 people with metastatic renal cell carcinoma treated with high-dose cimetidine 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 design³Inhorn L, Williams SD, Nattam S, Stephens D. High-dose cimetidine for the treatment of metastatic renal cell carcinoma. A Hoosier Oncology Group study. American Journal of Clinical Oncology. 1992 Apr;15(2):157-9.

Advanced melanoma: insufficient (conflicting) evidence of an effect on tumor response or survival among people with metastatic malignant melanoma treated with cimetidine, sometimes in addition to conventional treatments

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 tumor response or survival among people with metastatic malignant melanoma and performance status of 2 or lower treated with interleukin-2 and interferon-α 2b plus cimetidine compared to IL-2 and interferon-α 2b alone in a small controlled triala study design in which people are assigned to either an experimental group or a control group to compare the outcomes from different treatment; assignment is not random, and so this is not as strong a study design as a randomized controlled trial, but still stronger than an uncontrolled trial⁴Schmidt H, Geertsen PF, Fode K, Rytter C, Bastholt L, von der Maase H. Subcutaneous interleukin-2 and interferon-alpha plus cisplatin with and without prophylactic cimetidine in patients with metastatic malignant melanoma: a phase II study. Melanoma Research. 2000 Feb;10(1):66-77.
No evidence of an effect on survival among people with disseminated malignant melanoma treated with IFN-α 2A with cimetidine as an immunorestorative agent compared to IFN-α 2A alone in a small controlled trial⁵Creagan ET, Schaid DJ, Ahmann DL, Frytak S. Disseminated malignant melanoma and recombinant interferon: analysis of seven consecutive phase II investigations. Journal of Investigative Dermatology. 1990 Dec;95(6 Suppl):188S-192S.
No evidence of an effect on objective response or survival among people with metastatic malignant melanoma treated with 600 mg oral cimetidine 4 times a day in a small uncontrolled trial⁶Mandanas R, Schultz S, Scullin D, Einhorn LH. Phase II trial of cimetidine in metastatic melanoma. A Hoosier Oncology Group trial. American Journal of Clinical Oncology. 1991 Oct;14(5):397-9.
No evidence of a therapeutic effect among people with advanced malignant melanoma treated with cimetidine in addition to recombinant interferon alfa-2a compared to recombinant interferon alfa-2a alone in a small uncontrolled trial⁷Creagan ET, Ahmann DL, Frytak S, Long HJ, Chang MN, Itri LM. Three consecutive phase II studies of recombinant interferon alfa-2a in advanced malignant melanoma. Updated analyses. Cancer. 1987 Feb 1;59(3 Suppl):638-46.
Higher rates of objective tumor regressions and prolonged stable disease among people with metastatic malignant melanoma treated with interferon and cimetidine compared to earlier treatment with interferon alone in a small uncontrolled trial⁸Flodgren P, Borgström S, Jönsson PE, Lindström C, Sjögren HO. Metastatic malignant melanoma: regression induced by combined treatment with interferon [HuIFN-alpha(Le)] and cimetidine. International Journal of Cancer. 1983 Dec 15;32(6):657-65.
1 complete response of extensive pleural and pulmonary metastases for 16+ months and 2 partial regressions of soft tissue lesions for 7 and 21+ months among people with disseminated malignant melanoma treated with cimetidine as a single agent in a small uncontrolled trial⁹Morton RF, Creagan ET et al. Phase II studies of single-agent cimetidine and the combination N-phosphonacetyl-L-aspartate (NSC-224131) plus L-alanosine (NSC-153353) in advanced malignant melanoma. Journal of Clinical Oncology. 1987 Jul;5(7):1078-82.

Advanced ovarian cancer: preliminary evidence of better prognosis and overall survival after primary surgery among people with advanced serous ovarian carcinoma treated with platinum-based systemic chemotherapy and cimetidine

Considerably better prognosis and overall survival after primary surgery among people with advanced serous ovarian carcinoma treated with 4-6 cycles of platinum-based systemic chemotherapy and 800 mg cimetidine per day starting 2 weeks before surgery and continuing up to 2 years, with better outcomes among people with high expression of COX-2, compared to controls in a small controlled trial¹⁰Niwa K, Onogi K et al. Prognostic implications of cimetidine on advanced serous ovarian carcinoma related to cyclooxygenase-2 expression. Molecular Medicine Reports. 2008 Jan-Feb;1(1):119-22.

Breast cancer

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 tumor cell proliferation among people with breast cancer treated with cimetidine before surgery in a small study

Colorectal cancer

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 after surgical resection among people with colorectal cancer treated with cimetidine before, during, or after surgery

Substantially better survival after surgical resection with curative intent among people with colorectal cancer treated with cimetidine before, during, or after surgery compared to controls 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 5 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 effects¹²Deva S, Jameson M. Histamine type 2 receptor antagonists as adjuvant treatment for resected colorectal cancer. Cochrane Database of Systematic Reviews. 2012 Aug 15;(8):CD007814.
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 5-year overall survival among people with stage 1–3 colorectal cancer treated with 800 mg oral cimetidine twice a day for 5 weeks starting 2 to 7 days before curative-intent surgery compared to placeboa pill, medicine, or procedure—thought to be both harmless and ineffective—prescribed for the psychological benefit to the patient or as a sham treatment in a study to allow a comparison to a therapy of interest in a mid-sized RCT¹³Jameson MB, Michael Arendse et al. Final analysis of a randomized placebo-controlled double-blind phase II trial of perioperative cimetidine (CIM) in early colorectal cancer (CRC). Journal of Clinical Oncology. 2018;36(15_suppl):e15678-e15678.
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 better survival among people with recurrent colorectal cancer treated with cimetidine after curative resection of recurrent disease, but no evidence of an effect in other situations, compared to no cimetidine in a small controlled triala study design in which people are assigned to either an experimental group or a control group to compare the outcomes from different treatment; assignment is not random, and so this is not as strong a study design as a randomized controlled trial, but still stronger than an uncontrolled trial¹⁴Yoshimatsu K, Ishibashi K et al. [Can the survival of patients with recurrent disease after curative resection of colorectal cancer be prolonged by the administration of cimetidine?] [Article in Japanese]. Gan To Kagaku Ryoho. 2006 Nov;33(12):1730-2.
Better survival after curative resection of primary tumors among people with colorectal cancer, but only those not receiving blood transfusion and not developing postoperative infectious complications, treated with 100 mg intravenous ranitidine twice a day before skin incision and then 150 mg oral ranitidine twice a day for 5 years compared to placebo, but no evidence of an effect on survival among transfused patients, in a large RCT¹⁵Nielsen HJ, Christensen IJ, Moesgaard F, Kehlet H; Danish RANX05 Colorectal Cancer Study Group. Ranitidine as adjuvant treatment in colorectal cancer. British Journal of Surgery. 2002 Nov;89(11):1416-22.
Better survival and a weak trend toward conspicuous lymphocytic infiltration after elective colon or rectal excision for carcinoma among people with replication error negative tumors, but no evidence of an effect with other tumor types, treated with 800 mg cimetidine twice a day for 5 days before surgery in a mid-sized RCT¹⁶Kelly MD, King J et al. Randomized trial of preoperative cimetidine in patients with colorectal carcinoma with quantitative assessment of tumor-associated lymphocytes. Cancer. 1999 Apr 15;85(8):1658-63.
Substantially better 10-year survival after curative resection among people with colorectal cancer, limited to people with higher sialyl Lewis antigens X (sLx) and A (sLa), treated with 800 mg oral cimetidine per day in addition to 5-fluorouracil started 2 weeks after surgery and continuing for 1 year compared to 5-fluorouracil alone in a small RCT¹⁷Matsumoto S, Imaeda Y et al. Cimetidine increases survival of colorectal cancer patients with high levels of sialyl Lewis-X and sialyl Lewis-A epitope expression on tumour cells. British Journal of Cancer. 2002 Jan 21;86(2):161-7.
A weak trend toward better survival after resection with curative intent for adenocarcinoma of the colon or rectum among people with Dukes Stage C carcinoma treated with cimetidine compared to no cimetidine, but no evidence of an effect among people with disseminated disease in a mid-sized RCT¹⁸Svendsen LB, Ross C et al. Cimetidine as an adjuvant treatment in colorectal cancer. a double-blind, randomized pilot study. Diseases of the Colon and Rectum. 1995 May;38(5):514-8.

Gastrointestinal cancer

Colorectal cancer is listed separately.

Insufficient (conflicting) evidence of an effect on survival among people with stomach (gastric) cancer treated with cimetidine

H2 blockers combined with other therapies

Weak evidence of a better tumor response than expected among people with advanced renal cell carcinoma treated with lymphoblastoid interferon–α and oral cimetidine

Weak evidence of tumor response among people with metastatic renal cell carcinoma treated with coumarin and cimetidine

No evidence of tumor regression among people with hormone-refractory carcinoma of the prostate and bone metastases treated with oral coumarin and cimetidine

Weak evidence of progression-free survivalthe time during and after treatment of a disease that a patient lives without disease progression (worsening) for 16 months or longer in a man with pancreatic cancer treated with standard chemotherapy and TL-118

Preliminary evidence of better survival than expected after recurrence among people with glioblastoma with radiological disease progression treated with CLOVA cocktail in addition to temozolomide

Weak evidence of favorable responses and prognostic categories among people with advanced renal cell carcinoma treated with natural interferon-α, cimetidine, meloxicam, and candesartan or perindopril

Weak evidence of partial remission of metastases among people with metastatic renal cell carcinoma treated with cimetidine, cyclooxygenase-2 inhibitor, and renin-angiotensin system inhibitor

Cimetidine and interferon-α: weak evidence of a better tumor response than expected among people with advanced renal cell carcinoma treated with lymphoblastoid interferon–α and oral cimetidine

41% response rate among people with advanced renal cell carcinoma treated with lymphoblastoid interferon–α and 200 mg oral cimetidine 4 times a day 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 design, with better response among higher grade tumors and the best response to combined therapies seen with lung metastasis; the authors considered this “a definitively good response”²¹Kinouchi T, Saiki S et al. Treatment of advanced renal cell carcinoma with a combination of human lymphoblastoid interferon-alpha and cimetidine. Journal of Urology. 1997 May;157(5):1604-7.

Cimetidine and coumarin:

Weak evidence of tumor response among people with metastatic renal cell carcinoma treated with coumarin and cimetidine

No evidence of tumor regression among people with hormone-refractory carcinoma of the prostate and bone metastases treated with oral coumarin and cimetidine

Partial response among 3 of 50 people with locally advanced or metastatic renal cell carcinoma treated with 100 mg oral coumarin (1,2-benzopyrone) a day starting on day 1, escalating to 100 mg orally 4 times a day at progression, plus 300 mg oral cimetidine 4 times a day starting on day 15 in a small uncontrolled trial²²Dexeus FH, Logothetis CJ et al. Phase II study of coumarin and cimetidine in patients with metastatic renal cell carcinoma. Journal of Clinical Oncology. 1990 Feb;8(2):325-9.
Objective responses in 14 of 42 people and stable disease in another 12 people with metastatic renal cell carcinoma treated with 100 mg oral coumarin a day and after 14 days adding 300 mg cimetidine 4 times a day until disease progression in a small uncontrolled trial²³Marshall ME, Mendelsohn L et al. Treatment of metastatic renal cell carcinoma with coumarin (1,2-benzopyrone) and cimetidine: a pilot study. Journal of Clinical Oncology. 1987 Jun;5(6):862-6.
No evidence of tumor regression among people with stage D hormone-refractory carcinoma of the prostate and bone metastases treated with 100 mg oral coumarin a day and after 14 days adding 300 mg cimetidine 4 times a day until disease progression compared to baseline in a small uncontrolled trial²⁴Marshall ME, Butler K, Hermansen D. Treatment of hormone-refractory stage D carcinoma of prostate with coumarin (1,2-benzopyrone) and cimetidine: a pilot study. Prostate. 1990;17(2):95-9.

TL-118, a combination of low-dose-high-frequency cyclophosphamide, diclofenac, sulfasalazine, and cimetidine: weak evidence of progression-free survival for 16 months or longer in a man with pancreatic cancer treated with standard chemotherapy and TL-118

Progression-free survival of 16 months at the time of report in a man with pancreatic cancer treated with standard chemotherapy and TL-118; a clear elevation of tumor marker on stopping TL-118 dropped again with the renewal of TL-118 in a case studya descriptive and exploratory analysis of a person, group, or event regarding changes observed over time; because changes due to treatment are not compared to similar changes over time without treatment, a case study is considered a weak study design²⁵Breuer S, Maimon O, Appelbaum L, Peretz T, Hubert A. TL-118-anti-angiogenic treatment in pancreatic cancer: a case report. Medical Oncology. 2013;30(2):585.

Cimetidine, lithium, olanzapine, and valproate (CLOVA cocktail) with temozolomide: preliminary evidence of better survival than expected after recurrence among people with glioblastoma with radiological disease progression treated with CLOVA cocktail in addition to temozolomide

Better survival after recurrence among people with glioblastoma with radiological disease progression treated with CLOVA cocktail in addition to temozolomide compared to historical controls treated with temozolomide alone in a small comparison study²⁶Furuta T, Sabit H et al. Biological basis and clinical study of glycogen synthase kinase- 3β-targeted therapy by drug repositioning for glioblastoma. Oncotarget. 2017 Apr 4;8(14):22811-22824.

Interferon-α, cimetidine, cyclooxygenase-2 inhibitor and renin-angiotensin-system inhibitor (I-CCA therapy): weak evidence of favorable responses and prognostic categories among people with advanced renal cell carcinoma treated with natural interferon-α, cimetidine, meloxicam, and candesartan or perindopril

Favorable responses and prognostic categories among people with advanced renal cell carcinoma treated with natural interferon-α and 800 mg cimetidine, 10 mg meloxicam, and 4 mg candesartan or perindopril daily in a small uncontrolled trial²⁷Tatokoro M, Fujii Y et al. Phase-II trial of combination treatment of interferon-α, cimetidine, cyclooxygenase-2 inhibitor and renin-angiotensin-system inhibitor (I-CCA therapy) for advanced renal cell carcinoma. Cancer Science. 2011 Jan;102(1):137-43.

Cimetidine, cyclooxygenase-2 (COX-2) inhibitor, and renin-angiotensin-system inhibitor: weak evidence of partial remission of metastases among people with metastatic renal cell carcinoma treated with cimetidine, cyclooxygenase-2 inhibitor, and renin-angiotensin system inhibitor

Partial remission of metastases among people with metastatic renal cell carcinoma treated with cimetidine, cyclooxygenase-2 inhibitor, and renin-angiotensin system inhibitor in 3 case studies²⁸Tatokoro M, Fujii Y et al. Favorable response to combination treatment of cimetidine, cyclooxygenase-2 inhibitor and renin-angiotensin system inhibitor in metastatic renal cell carcinoma: report of three cases. International Journal of Urology. 2008 Sep;15(9):848-50.

Optimizing your body terrain

Do cimetidine and other H2 blockers 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 ›

Immune function

Increased immune system activation is not always beneficial, so your oncology team needs to determine whether immune activation would be favorable in your situation.

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 higher markers of immune activation among people with cancer treated with cimetidine

H2 blockers combined with other therapies

Cimetidine and coumarin: 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 immunologic parameters among people with locally advanced or metastatic renal cell carcinoma treated with oral coumarin and cimetidine in a small study

Managing side effects and promoting wellness

Are cimetidine and other H2 blockers 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.

Both type 1 and 2 histamine receptor antagonists are used to treat hypersensitivity reactions to antineoplastic agents.³⁶Syrigou E, Syrigos K, Saif MW. Hypersensitivity reactions to oxaliplatin and other antineoplastic agents. Current Allergy and Asthma Reports. 2008 Mar;8(1):56-62; Saif MW. Hypersensitivity reactions associated with oxaliplatin. Expert Opinion on Drug Safety. 2006 Sep;5(5):687-94; Bookman MA, Kloth DD, Kover PE, Smolinski S, Ozols RF. Short-course intravenous prophylaxis for paclitaxel-related hypersensitivity reactions. Annals of Oncology. 1997 Jun;8(6):611-4.

Gastrointestinal symptoms

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 less liver dysfunction but 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 diarrhea after treatment with gefitinib among people with non-small cell lung cancer treated with histamine type 2 receptor antagonists in a small study

Skin and tissue symptoms

No evidence of an effect on skin toxicity after treatment with gefitinib among people with non-small cell lung cancer treated with histamine type 2 receptor antagonists in a small study

H2 blockers combined with other therapies

Coumarin and cimetidine: 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 less bone pain and analgesic use among a subset of people with hormone-refractory carcinoma of the prostate and bone metastases treated with oral coumarin and cimetidine

Reducing cancer risk

Are cimetidine and other H2 blockers linked to lower risks of developing cancer or of recurrence? We present the evidence.

Colorectal cancer

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 recurrence of colorectal cancer treated with cimetidine around the time of surgery

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 adenoma risk or multiple adenoma formation after removal of adenoma(s) among people using either H1 or H2 blockers in a combined analysis of studies

Recurrence: insufficient (conflicting) evidence of an effect on recurrence of colorectal cancer treated with cimetidine around the time of surgery

No evidence of an effect on 5-year 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 stage 1–3 colorectal cancer treated with 800 mg oral cimetidine twice a day for 5 weeks starting 2 to 7 days before curative-intent surgery compared to placeboa pill, medicine, or procedure—thought to be both harmless and ineffective—prescribed for the psychological benefit to the patient or as a sham treatment in a study to allow a comparison to a therapy of interest 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 effects⁴⁰Jameson MB, Michael Arendse et al. Final analysis of a randomized placebo-controlled double-blind phase II trial of perioperative cimetidine (CIM) in early colorectal cancer (CRC). Journal of Clinical Oncology. 2018;36(15_suppl):e15678-e15678.
Substantially longer time to recurrence and better survival after surgical resection of the tumor among people with stage 3 colorectal cancer treated with cimetidine around the time of surgery and continuing for an average of 369 days, in addition to chemotherapy, compared to chemotherapy alone, with stronger effects among people taking cimetidine for longer durations or with larger cumulative doses, in a small 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 study⁴¹Ali AH, Hale L et al. The effect of perioperative cimetidine administration on time to colorectal cancer recurrence. American Journal of Therapeutics. 2018 Jul/Aug;25(4):e405-e411.

Cancer risk: no evidence of an effect on adenoma risk or multiple adenoma formation after removal of adenoma(s) among people using either H1 or H2 blockers in a combined analysis of studies

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 lower risk of multiple recurrent adenomas, but no evidence of an effect on recurrent adenoma risk after removal of adenoma(s) among people using H2 blockers in a pooled analysis of 3 observational studies⁴²Robertson DJ, Burke CA et al. Histamine receptor antagonists and incident colorectal adenomas. Alimentary Pharmacology & Therapeutics. 2005 Jul 15;22(2):123-8.

Lung cancer

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 moderately lower risk of lung cancer, especially lung adenocarcinoma, among people with type 2 diabetes using histamine-2 receptor blockers

Keep reading about H2 blockers

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Nancy Hepp, MS

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Laura Pole, MSN, RN, OCNS

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Susan Yaguda, MSN, RN

Manager at Atrium Health’s Levine Cancer Institute and CancerChoices Clinical Consultant

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Last update: May 9, 2024

Last full literature review: May 2023

CancerChoices provides information about integrativein 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 psychosocialtherapy, and acupuncture therapies and self carelifestyle 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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Cimetidine and Other H2 Blockers

How can H2 blockers help you? What the research says

Improving treatment outcomes

Optimizing your body terrain

Managing side effects and promoting wellness

Reducing cancer risk

Keep reading about H2 blockers

Author

Nancy Hepp, MS

Laura Pole, MSN, RN, OCNS

Reviewer

Susan Yaguda, MSN, RN

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References
1	Burtin C, Noirot C et al. Clinical improvement in advanced cancer disease after treatment combining histamine and H2-antihistaminics (ranitidine or cimetidine). European Journal of Cancer & Clinical Oncology. 1988 Feb;24(2):161-7.
2	Kinouchi T, Sakamoto J et al; Immunotherapy Oncology Group for Renal Cell Carcinoma. Prospective randomized trial of natural interferon-alpha versus natural interferon-alpha plus cimetidine in advanced renal cell carcinoma with pulmonary metastasis. Journal of Cancer Research and Clinical Oncology. 2006 Aug;132(8):499-504.
3	Inhorn L, Williams SD, Nattam S, Stephens D. High-dose cimetidine for the treatment of metastatic renal cell carcinoma. A Hoosier Oncology Group study. American Journal of Clinical Oncology. 1992 Apr;15(2):157-9.
4	Schmidt H, Geertsen PF, Fode K, Rytter C, Bastholt L, von der Maase H. Subcutaneous interleukin-2 and interferon-alpha plus cisplatin with and without prophylactic cimetidine in patients with metastatic malignant melanoma: a phase II study. Melanoma Research. 2000 Feb;10(1):66-77.
5	Creagan ET, Schaid DJ, Ahmann DL, Frytak S. Disseminated malignant melanoma and recombinant interferon: analysis of seven consecutive phase II investigations. Journal of Investigative Dermatology. 1990 Dec;95(6 Suppl):188S-192S.
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