We’re busy reviewing the evidence on propranolol and other beta blockers. While we’re working, we share the original summary from our predecessor website, Beyond Conventional Cancer Therapies.

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Propranolol and Other Beta-Blockers

Key Points

  • Before using this therapy, consult your oncology team about interactions with other treatments and therapies. Also make sure this therapy is safe for use with any other medical conditions you may have.
  • Propranolol is a drug approved by the FDA for several diseases and conditions.
  • It’s used off-label in cancer treatment.
  • CancerChoices sees propranolol as an interesting and promising drug and is impressed with the early evidence to support re-purposing its use in cancer.
  • Laboratory and clinical effects of propranolol in cancer treatment include inhibiting cancer cell proliferation, decreasing cancer cell migration and invasion, increasing cancer cell death, and inhibiting the growth of blood vessels to feed tumors.
  • Propranolol shows promise in enhancing the effectiveness of conventional treatments, boosting the immune system’s cancer-fighting mechanisms, reducing metastases, extending survival, and reducing symptoms.
  • Propranolol may also reduce stress and its cancer-promoting effects.
  • Propranolol is generally safe and usable long-term, although several cautions and interactions are noted.

Propranolol is a beta blocker (non-selective beta-adrenergic receptor antagonist) being used off-label for cancer treatment by some integrative oncologists. Off-label use is a drug’s application for a disease or condition that has not yet received FDA approval. Every US state allows for drugs to be used off-label as long as there is enough evidence to support its use.

Most of the human evidence in cancer to date is from case reports, but a number of clinical trials for several cancers are in progress.

The Cancer Prevention and Treatment Fund recommends that patients already taking beta blockers for a heart condition should continue use if they are also diagnosed with cancer. However, some caution against use only in cancer until stronger evidence from controlled clinical trials shows its efficacy.

Some research suggest that people not already using beta blockers who are diagnosed with non-small cell lung cancer or early breast cancer may want to ask their healthcare providers whether to take beta blockers for two days before and three days after cancer surgery.1

Treating the Cancer

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

Clinical Evidence

An extensive review in 2016 found proprnolol exhibits anti-metastatic effects in breast and ovarian cancers. Evidence particularly indicates that propranolol works at multiple points in the metastatic cascade, especially in the setting of the post-surgical wound response (see more in How It Works at right).2

Impacts on Survival
  • Prolonged survival of cancer patients with use, especially patients with early-stage cancer treated primarily with surgery3
  • Angiosarcoma: Extended progression-free and overall survival among seven patients with advanced/metastatic/recurrent angiosarcoma4
  • Breast cancer:
    • Mixed results regarding survival:
      • Improved survival and decreased risk of breast cancer metastasis among postmenopausal women undergoing surgery for early primary triple-negative breast cancer5
      • Reduced breast cancer progression and mortality in some reviews6
      • Reduced breast cancer deaths but not overall mortality in one meta-analysis7
      • No survival advantage in other large pooled analyses8
      • Fewer metastatic biomarkers among people with early-stage breast cancer with 11 days of treatment with propranolol and a COX-2 inhibitor (etodolac), beginning five days before surgery in a small RTC9
    • Reduced toxicity to the heart and improved survival in female breast cancer patients undergoing trastuzumab/anthracycline treatment.10
    • Lower markers of cancer progression and immune activation against tumor cells among people with early-stage surgically resectable breast cancer with one week of beta-blocker use before surgery in a small RCT11 
  • Lung cancer:
    • Better distant metastasis-free survival among people with non-small-cell lung cancer receiving definitive radiotherapy with use of beta blockers in a mid-sized observational study12
    • No effect on survival among people with lung cancer with use of beta blockers either before or after diagnosis in a large observational study13
  • Ovarian cancer:
    • Substantial (doubling or more) of overall survival among women with epithelial ovarian cancer with use of non-selective beta blockers during chemotherapy compared to no use of beta blockers or use of selective beta blocker in a large observational study14
    • 54% lower mortality among women with epithelial ovarian cancer undergoing cytoreductive surgery followed by platinum-based chemotherapy with use of beta blockers for more than six months in a mid-sized observational study15
    • reviews have concluded that beta blockers, especially nonselective beta blockers, provided a significant survival advantage,16 while no benefit was found with selective beta blockers17
  • Pancreatic cancer: Increased progression-free survival when adding propranolol/etodolac (a nonsteroidal anti-inflammatory drug, or NSAID) to treatment with gemcitabine and albumin-bound (nab) paclitaxel in a small study18
  • Prostate cancer: No decreased risk of mortality either from prostate cancer or from all causes among men newly diagnosed with non-metastatic prostate cancer19
Reduced Metastasis
  • Lower recurrence among people with stage 2 breast cancer (but not stage 3), but no better survival, with use of beta blockers at the time of surgery in a large observational study20
  • A 2016 review suggested that propranolol be added to standard of care for nonmetastatic cancers as a strategy to reduce the rate of metastasis.21
Enhancer of Conventional Treatments
  • Increased sensitivity of some cancers to certain chemotherapy drugs with propranolol; use increased the effectiveness of 5-FU and paclitaxel in breast cancer treatment22
  • Increased effectiveness of radiotherapy as well as chemoradiotherapy combinations with propranolol in case studies23
Lab and Animal Evidence

Click or tap to open.

Anticancer Activity

In lab, animal and human studies and in clinical data, evidence suggests that propranolol has potent anticancer effects. An extensive review in 2016 found these effects:29

  • Interferes with cancer cell growth and invasion, reducing proliferation and increasing cell death (apoptosis)
  • Reduces tumor angiogenesis (development of new blood vessels)

Beta blockers sensitized ovarian cancer cells to chemotherapeutic agents, enhancing chemotherapy effects in preclinical studies.30

Propranolol decreased proliferation, migration, invasion and metastasis in preclinical studies when used with metformin.31

How It Works

Propranolol seems to exert its anticancer activity in several ways:

  • Inhibiting cancer cell proliferation24
  • Decreasing cancer cell migration and invasion25
  • Causing cell death (apoptosis)26
  • Inhibiting growth of new blood vessels (angiogenesis)27
Propranolol and Surgery

Surgery may be linked to an increased risk of metastasis.32 The flood of stress hormones that often accompany surgery may be one contributor to this increase. Some beta blockers reduce the stress response and may therefore lead to lower risk of metastasis. Preliminary evidence supports this line of thinking.33

One study found that propranolol administered peri-operatively may reduce the establishment of brain metastases in patients with triple-negative breast cancer.34 A 2016 review suggested that propranolol be added to standard of care for nonmetastatic cancers as a strategy to reduce the rate of metastasis.35

Propranolol also appears to work synergistically with a COX-2/PGE2 inhibitor such as ketorolac or etodolac. A 2016 study suggests focusing further study of this effect on cancers in which post-surgical distant metastases are frequent.36

  • Breast cancer
  • Osteosarcoma
  • Head and neck cancers
  • Upper gastrointestinal cancers (such as esophageal or stomach)
  • Non-small cell lung cancer
  • Ovarian cancer

Managing Side Effects and Promoting Wellness

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

  • Reduced risk of heart failure and markers of cardiotoxicity in patients undergoing anthracycline chemotherapy, especially with carvedilol use.37
  • Reduced cardiotoxicity and improved survival in female breast cancer patients undergoing trastuzumab/anthracycline treatment.38
  • Reduced emotional distress in newly diagnosed cancer patients.39
  • Reduced pain and neuropathy and increased weight gain in a small study of people with locally advanced pancreatic cancer receiving gemcitabine and nab-paclitaxel with the addition of a propranolol/etodolac regimen40
  • Reduced resting energy expendituren in a small study of cancer patients with progressive weight loss due to solid malignant tumors41
  • Reduced levels of emotional distress, including intrusive thoughts related to cancer diagnosis,  with propranolol in a study of women with breast cancer or colorectal cancer42

Reducing Risk

Reducing the risk of developing cancer or the risk of recurrence

Clinical Evidence

Reduced risks of cancers of the head and neck, esophagus, stomach, colon and prostate.43

Decreased risk of breast cancer-related recurrence among postmenopausal women with early primary triple-negative breast cancer,44 but no overall reduced risk of recurrence.45

  • Substantially lower recurrence of melanoma in a small prospective study46

Optimizing Your Terrain

  • Reduced effects of psychological stress on primary tumor growth with propranolol47
  • Reduced tumor-promoting effects of catecholamines (hormones produced by the adrenal glands) in retrospective clinical studies with ovarian cancer48
  • Enhanced immune system cancer-fighting mechanisms, such as increasing the ability of certain immune cells (macrophages) to consume cancer cells by a process called phagocytosis49
Stress and Beta Blockers

Chronic stress triggers a chain of internal events that protects cancer cells from automatic destruction when they break away from the primary tumor. Increased levels of epinephrine and norepinephrine (stress hormones) allow malignant cells to safely leave the primary tumor, avoid cell death, and proceed to the next step of metastasis and progression.

When norepinephrine contacts the beta-adrenergic (ADRB) receptor on tumor cells, it activates Src, a gene which regulates cancer cell survival proteins. This activation causes a chain reaction inside cells that promotes cell survival, mobility, invasion of neighboring tissue and creation of new blood vessels to supply the tumor. Beta blockers plug the ADRB receptor and prevent activation by norepinephrine and other hormones.

  • Propranolol inhibited the “priming effect” of repeated social disruption stress, in which natural killer (NK) cells increase in both numbers and cell-killing activity..50
  • Effects in ovarian cancer:
    • A 2015 study found that stress hormones fuel progression of ovarian and other cancers and that beta blockers might be a new way to counter that effect. Findings:51
    • Stressing mice with ovarian cancer causes their tumors to grow and spread more quickly. Propranolol can block this effect.
  • Effects with breast cancer:
    • Propranolol reduced activity of hexokinase-2, an enzyme important for tumor metabolism.52
    • Salbutamol inhibited invasion of tumor cells and decreased expression of pro-metastatic genes in cell studies.53
  • Propranolol blocked the norepinephrine-induced migration of prostate cancer cells in animal studies.54

Access

Propranolol is available by prescription as both standard and extended-release tablets, an oral solution, and an IV injection. It is available globally in generic form. Estimated cash price for sixty 40-mg tablets ranges from about $40 to $75. Significant discounts are available using prescription drug discount apps such as GoodRX.

Cautions

Propranolol generally has low toxicity and can be used for many years in long-term treatment.55 However, some cautions should be heeded:

  • Calcium-channel blocking drugs: Caution is warranted using propranolol with calcium-channel blocking drugs, particularly IV verapamil, in patients with severe cardiomyopathy, congestive heart failure, or recent myocardial infarction (heart attack) due to the negative inotropic and chronotropic action of these drugs (actions affecting the force of contractions or heart rate and rhythm).56
  • Sudden cessation of use is not advised, especially in ischemic heart disease. In this case, gradually taper the dose.
Adverse Events / Side Effects
Common

· Insomnia
· Fatigue
· Cold extremities
· Raynaud’s syndrome

Less common

· Nausea
· Vomiting
· Diarrhea

Rare

· Heart failure
· Heart block
· Hypotension (low blood pressure)
· Worsening of symptoms of psoriasis, asthma and psychosis

Contraindications / Do Not Use If

Patients with these conditions should not use propranolol:57

  • Hypotension (low blood pressure)
  • Asthma
  • Uncontrolled heart failure
  • Severe peripheral artery disease
  • Metabolic acidosis
  • Cardiogenic shock

Use is not recommended in pregnancy and during lactation.

Interactions

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) to share with your doctor and pharmacist. Do not start, stop or change the dosage of any medicines without your doctor’s approval.58

A study involving both animal and human cells demonstrated that two drugs that stimulate the beta adrenergic receptor, isoprenaline and salbutamol, unexpectedly inhibited breast cancer and that propranolol reversed this inhibition.59

Specific Drug Interactions

Some products that may interact with this drug:

  • Alpha blockers (such as prazosin)
  • Aluminum hydroxide
  • Anticholinergics (such as atropine, scopolamine)
  • Chlorpromazine
  • Drugs affecting liver enzymes that remove propranolol from your body (such as cimetidine, St. John’s wort, certain SSRI antidepressants including fluoxetine/paroxetine/fluvoxamine, HIV protease inhibitors including ritonavir, rifamycins including rifabutin)
  • Epinephrine
  • Fingolimod
  • Haloperidol
  • Mefloquine
  • Rizatriptan
  • Theophylline
  • Thioridazine
  • Thyroid hormones (such as levothyroxine)
  • Warfarin
  • Other drugs to treat high blood pressure (such as clonidine, hydralazine, methyldopa, reserpine)
  • Other heart medications (such as digoxin, disopyramide, propafenone, quinidine)

Integrative Programs, Protocols and Medical Systems

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

Programs and protocols

Lemole, Mehta & McKee stress management stress management protocol60

Commentary

BCCT advisor Dwight McKee, MD, an integrative oncologist and co-author of After Cancer Care, February 20, 2017:

“I’ve advocated for propranolol (which seems to work the best compared with more ‘modern’ beta blockers), implemented as soon as possible after diagnosis, since a new diagnosis of cancer is a highly stressful event, and we have both experimental and clinical evidence that stress acts as a tumor promoter, although it doesn’t appear to be involved in the initiation of malignancy.

I have recommended propranolol for anyone diagnosed with cancer who is experiencing high levels of stress from their diagnosis, and all of the logistics involved in seeing different doctors, and making treatment decisions often with a sense of time pressure (the psychological emergency of a cancer diagnosis). It takes time for people to learn and become proficient with stress management techniques, so I see propranolol as “training wheels” until they are in calmer waters and well on their way to practicing an “anticancer lifestyle”, which includes learning and practicing stress management techniques.

A typical dose and schedule would be 40 mg twice daily, but I would start with 10 mg once a day, then 10 mg twice a day and increase by 10 mg every few days (as tolerated) up to 40 mg twice daily, if that dose and schedule is well tolerated. Some people will get dizzy from low blood pressure from too high an initial dose, so it‘s always a good idea to start low and increase by 10 mg every few days. I would use the same approach for a patient with angiosarcoma.

The older beta blockers seem to work better for this application than the newer ones. Contraindications are severe asthma (propranolol can block the rescue effects of adrenaline) and very low baseline blood pressure. People with high blood pressure can start with higher dose, even at 40 mg twice daily. If they are taking another beta-blocker, I would suggest they work with a doctor in converting over to Inderal.

Also known by these names

  • Angilol
  • Ciplar
  • Inderal
  • Syprol
  • Hemangeol (special oral formulation for the treatment of infantile hemangioma, or vascular tumors)

Resources

References

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