Propranolol in Oncology

Prepared for an international off-label drugs in oncology study-support library and discussion with oncology, prescribing, integrative and pharmacy teams. Seven uploaded primary papers on pancreatic, prostate, bone-metastasis and myeloma/transplant research are incorporated into this report.

Overview

Propranolol is a non-selective beta-blocker: it competitively blocks β1- and β2-adrenergic receptors, reducing responses to adrenaline (epinephrine) and noradrenaline (norepinephrine). Its established uses include cardiovascular conditions, migraine prevention and essential tremor; indications differ by product and country. Its proposed oncology roles extend well beyond anxiety relief or nerve-to-cancer mitochondrial transfer.

Cancer research investigates whether beta-blockade can reduce adrenergic support for tumour cells, change the stromal environment, influence immune suppression, interrupt nerve-growth feedback loops or improve a specific treatment combination. Human evidence includes small randomised biomarker trials, an exploratory colorectal recurrence signal and uncontrolled combination studies.

At a glance

• Breast: short preoperative treatment changed tumour biomarkers; improved survival was not established. [5,6]

• Colorectal: a small propranolol–etodolac trial reported fewer recurrences. [7,8]

• Pancreas: propranolol has cell/organoid findings; the key mouse gemcitabine survival experiment used the experimental β2 blocker ICI 118,551, not propranolol. [12]

• Bone: propranolol reduced the additional bone colonisation associated with restraint stress in mice; no significant benefit was seen in unstressed controls. [13]

• Prostate: denervation, receptor deletion, signalling inhibition and propranolol-plus-castration experiments answer different questions. [14–16]

• Myeloma: a 25-patient transplant trial changed immune gene-expression markers; relapse and survival benefit were not established. [17,18]

• Melanoma/angiosarcoma: early combination activity is encouraging but small studies do not prove added benefit. Angiosarcoma monotherapy did not meet its efficacy criterion. [9–11]

• Safety: asthma/bronchospasm, slow pulse, low BP, fasting/hypoglycaemia, interacting medicines and abrupt withdrawal are central issues. [1,2]

Repurposing rationale and essential distinctions

Adrenergic signals act on cancer cells and on surrounding cells such as osteoblasts, blood-vessel cells, immune cells and nerves. The same receptor pathway can have different effects in different tissues, clones and stages. "Nerve-targeting" is therefore too broad to identify a treatment or predict a response. [12–16]

Observational beta-blocker findings must also be separated from propranolol-specific evidence. Patients taking these medicines may differ in cardiac disease, other treatments, age, treatment timing and healthcare use. Non-selective beta-blockers are not identical drugs. Meta-analyses can repeatedly include the same underlying cohorts, so large publication counts do not necessarily mean independent confirmation. [4,12]

Stress biology is not patient blame

Mechanisms of action

Plain-language explanation

Propranolol prevents some adrenaline and noradrenaline messages from being received at beta receptors. Researchers ask whether this reduces signals that help a cancer cell survive, encourages its surrounding tissue to support it, or weakens anticancer immune responses. It does not switch off all nerves, remove every stress hormone, block muscarinic receptors or mechanically close mitochondrial-transfer nanotubes. [1–3,12–20]

Evidence by cancer type

This is an evidence map, not a recommendation ranking. A "negative" finding can limit a particular regimen without ruling out every possible schedule. Equally, a positive cell or mouse result cannot establish a human treatment benefit.

What the 2025 review does—and does not—count

O'Logbon et al. included 31 publications: seven classified as randomised/clinical trial reports and 24 reviews/meta-analyses, with searches to July 2024. These are not 31 independent propranolol trials. A retrospective beta-blocker analysis nested within a randomised trial of another treatment does not mean patients were randomised to beta-blockade. Some primary cohorts recur across reviews. [4]

For example, a larger breast-cancer class-level meta-analysis summarised in that review found no statistically significant association with breast-cancer death (HR 0.90, 95% CI 0.78–1.04) or recurrence (HR 0.87, 95% CI 0.71–1.08). A propranolol-specific pooled cohort analysis also did not establish lower breast-cancer-specific mortality after diagnosis (adjusted HR 0.94, 95% CI 0.77–1.16). These results should accompany—not be hidden behind—the preclinical rationale. [4]

Detailed original-paper findings

Breast cancer and the peri-operative window

Hiller et al. randomised 60 patients with surgically resectable breast cancer to escalating oral propranolol (80–160 mg/day) or placebo for seven days before surgery. The primary endpoint concerned tumour gene expression, not recurrence. Mesenchymal gene expression fell (P = 0.002), without a significant epithelial-gene change. Bioinformatic analyses implicated changes in Snail/Slug, NF-κB/Rel and AP-1 activity and immune-cell recruitment. [5]

A separate Israeli programme tested propranolol plus etodolac in 38 women around surgery and reported changes in metastasis-associated gene expression and immune/inflammatory markers. Related publications from that cohort should not be counted as independent trials. The combination design cannot identify the contribution of propranolol alone. [6,8]

Colorectal cancer and the etodolac combination

The COMPIT pilot randomised 34 newly diagnosed, non-metastatic colorectal cancer patients to propranolol plus etodolac or placebo for 20 perioperative days, starting five days before surgery. The published five-year report gave recurrence counts of 2/16 versus 9/18 (12.5% versus 50%; P = 0.033); deaths were 2/16 versus 4/18, with no significant mortality difference. The small sample makes the apparent effect size unstable. [7]

The 2026 Sakis report pooled safety information from four randomised cohorts: breast n = 38, colorectal n = 34 and n = 46, and pancreatic n = 30; 148 patients altogether. The newer colorectal and pancreatic trials were still ongoing in that report. Its exploratory eight-year colorectal analysis reports 2/15 versus 9/18 and a DFS difference, with insufficient power for a reliable survival estimate. The five- and eight-year denominators differ and must not be silently interchanged. Longer follow-up of the same small cohort is not independent replication. [8]

Pancreatic cancer: nerves, neurotrophins and gemcitabine

Renz et al. combined genetically engineered pancreatic models, cell and organoid experiments, nerve co-cultures and retrospective patient data. Their proposed loop was: catecholamines activate ADRB2 → cancer cells secrete neurotrophins → nerves grow into the tumour → local noradrenaline delivery increases → further growth-supporting signalling. Mouse models prominently involved NGF; human epithelial samples more often expressed BDNF. [12]

Breast cancer bone colonisation: the Campbell study

Campbell et al. injected one million bone-seeking, GFP-labelled MDA-MB-231VU human breast cancer cells into the left cardiac ventricle of young female athymic nude mice. This bypassed escape from a primary breast tumour and addressed circulation-to-bone colonisation. Restraint stress was applied two hours daily, six days per week, beginning two weeks before cell injection and continuing for four weeks afterwards. [13]

Propranolol was provided ad libitum in drinking water at 0.5 g/L. This is a water concentration—not a fixed mg/kg/day intake and not a human oral dose. In stressed mice, propranolol significantly reduced radiographic bone-lesion involvement/area and histological bone tumour occurrence. In unstressed controls, the reduction was not statistically significant. The result is therefore not "propranolol prevented all bone metastasis." [13]

What made the mechanism persuasive

• The β-agonist isoproterenol stimulated osteoblast-lineage cells to express RANKL, which encouraged RANK-expressing cancer cells to migrate. [13]

• Blocking beta signalling specifically in cancer cells did not remove the migration-promoting effect of stimulated osteoblasts; the host bone environment was central. [13]

• A RANKL decoy receptor (OPG) blocked the increased migration; reducing cancer-cell RANK expression by about 85% blunted the agonist-associated increase in bone colonisation. This distinguished the cancer-cell migration mechanism from bone turnover alone. [13]

• Isoproterenol pretreatment of the host increased the number of bones/tumours involved; treatment after injection mainly increased lesion size and tumour burden. This was timing work with an agonist, not a post-metastasis propranolol rescue trial. [13]

Counting matters: the radiographic "lesion number" method counted the number of involved long bones among six examined, rather than every individual focus. The selected bone-seeking clone and T-cell-deficient host also limit generalisation. Direct adrenergic stimulation actually reduced growth of these cells in some extraskeletal settings, illustrating why "all adrenergic activity feeds all cancers" is inaccurate. [13]

What it supports: a preclinical rationale for blocking stress-associated support from the bone niche, particularly early colonisation, discussed further in Integrative and Off-Label Strategies. What it does not show: shrinkage of established human bone metastases, pain control, survival benefit, or efficacy of propranolol plus denosumab. OPG and RANK knockdown are not clinical denosumab-combination evidence. [13]

5E. Prostate cancer: three different experimental questions

1. Magnon 2013 — can autonomic nerves regulate tumour development?

Chemical/surgical sympathectomy and host β2/β3 receptor deletion impaired early prostate tumour development. In Hi-Myc mice, early intervention mattered; sympathectomy at two months or later did not reduce tumourigenesis, and invasion was not reduced by sympathetic ablation. Separate cholinergic experiments implicated stromal CHRM1 in invasion and dissemination. Muscarinic antagonism/receptor deletion—not propranolol—produced the reported mouse survival effects. [14]

The human component examined tissue from 43 prostatectomy patients. Nerve-density associations with aggressiveness/recurrence did not remain statistically significant after adjustment including PSA and Gleason score. No metastatic events had been documented in that cohort at reporting. This is foundational mechanism evidence, not a propranolol trial or an established nerve-density test for treatment selection. [14]

2. Dwivedi 2021 — can noradrenaline promote neuroendocrine-like change?

Noradrenaline at 50 micromolar and above produced neuroendocrine-like morphology and marker changes in DU145 and LNCaP cells; 10 micromolar did not produce those morphological changes over the tested period. The authors explicitly described the higher exposures as supraphysiological. One-hour pretreatment with 50 micromolar propranolol inhibited several noradrenaline-induced markers, with effects differing by cell line. [15]

In the orthotopic LASCPC-01 model, there were four mice per group: saline control, castration, and castration plus propranolol. Propranolol was given intraperitoneally at 20 mg/kg, beginning seven days after tumour inoculation for a 21-day treatment period. Only one of four combination-treated animals developed a detectable tumour at endpoint, versus all animals in the other groups. However, the implanted cells were already a neuroendocrine prostate cancer line, so this experiment did not prove prevention of treatment-induced conversion from ordinary adenocarcinoma. [15]

The animal experiment lacked a propranolol-only arm: additional benefit compared with castration was observed, but formal drug–castration synergy cannot be isolated. Tiny groups, high cell-culture concentrations and injection exposure limit translation. This is not clinical evidence for adding propranolol to enzalutamide, abiraterone or another specific androgen-axis drug. [15]

3. Alaskar 2023 — does propranolol inhibit the intended signalling?

In C42, PC3, LNCaP and 22Rv1 cell models, adrenaline activated PKA readouts such as phosphorylated CREB and VASP. AKT behaviour differed: adrenaline-triggered AKT activation was clearer in PTEN-positive 22Rv1, whereas PTEN-negative lines had substantial baseline activity. Propranolol reduced adrenaline-induced signalling, with effects depending on concentration ratio, marker, cell line and time. Some signals required longer than 30 minutes to return to baseline. [16]

Intraperitoneal propranolol at 0.5 or 1.5 mg/kg reduced stress-associated CREB phosphorylation in mouse prostate. The paper also reports a preliminary mean plasma concentration of 43 nanomolar two hours after a 40 mg tablet in pilot human work. This does not establish a therapeutic tumour level: the authors explicitly call for prostate-tissue/catecholamine measurements and tumour pathway assessment. A tenfold culture ratio must not be turned into a human dosing rule. [16]

5F. Multiple myeloma and autologous transplantation

Knight et al. randomised 25 adults undergoing their first autologous HCT for myeloma: 12 to propranolol and 13 to control. Standard transplant care included melphalan conditioning. This was a biomarker trial, not a study of propranolol replacing myeloma treatment. Propranolol began at 20 mg twice daily approximately one week before transplant and could rise to 40 mg twice daily after one week if tolerated, continuing through day +28. [17]

The CTRA composite captures a stress-associated pattern of inflammatory versus antiviral/antibody-related gene expression. The adjusted comparison reported an approximately 25% lower change in the composite relative to control (P = 0.017). This is not a 25% reduction in relapse or mortality. Blood samples were collected at baseline, day −2 (before melphalan) and day +28; the primary contrast compared baseline with the average of the two follow-ups. [17]

Transcript-origin analyses suggested lower classical CD16-negative monocyte/myeloid-associated expression and relatively greater CD34-positive stem/early-progenitor-associated expression. These are bioinformatic inferences from mixed blood-cell gene expression—not direct counts of functional stem cells, proof of immune restoration, or direct demonstration of a changed marrow niche. [17]

The clinical figures above are from Knight et al. The trial was not powered to establish progression-free or overall survival, and its supplementary medicine exclusion tables were not available in the uploaded main PDF. [17]

Johnson et al. subsequently analysed Rap1A/Rap1B in samples from this same 25-patient trial. Propranolol did not significantly alter measured total or prenylated Rap1A/Rap1B levels. Higher baseline Rap1B correlated with slower platelet engraftment overall and in controls; the correlation was not significant within the treated subgroup. A significant result in one subgroup and a non-significant result in another does not itself establish a significant treatment interaction. The authors acknowledge that their small sample did not allow a definitive between-group mechanism comparison. [18]

These are one trial and a correlative follow-up—not two independent positive clinical trials. The appropriate interpretation is human molecular proof of concept plus exploratory clinical/mechanistic observations, with no established survival benefit. [17,18]

5G. Melanoma, immunotherapy and angiosarcoma

Gandhi et al. treated nine checkpoint-treatment-naïve metastatic melanoma patients with pembrolizumab and propranolol in three dose cohorts: 10, 20 or 30 mg twice daily. Seven had objective responses (78%), all partial responses in the patient table. There was no pembrolizumab-only control and no intra-patient dose escalation; the response rate cannot show how much propranolol added. Thirty mg twice daily was selected for further research. [9]

No protocol-defined dose-limiting toxicities were recorded, but that does not mean no serious events. All nine had treatment-related adverse events; two discontinued for toxicity, including HLH in a complex infection context and labyrinthitis/hearing toxicity. Attribution was uncertain and biomarkers were heterogeneous. A lower propranolol dose than in some other trials was used, undermining claims that every oncology regimen needs 80–160 mg/day. [9]

Pasquier et al. studied transformed endothelial models and then seven patients with advanced angiosarcoma receiving propranolol plus vinblastine/methotrexate, followed in some cases by multi-drug maintenance. All seven were reported to respond. Median PFS was 11 months and OS 16 months, but there was no comparison group and treatment was heterogeneous. The paper identified formal in vitro synergy with vinblastine; paclitaxel was largely additive and doxorubicin showed slight antagonism in those models. [10]

The later PropAngio monotherapy study used escalating propranolol for three to six weeks in 14 patients; two met the study's clinical-response definition and the prespecified efficacy threshold was not reached. These were "clinical responses" under the study definition, not automatically two RECIST partial responses. The combination series and negative monotherapy criterion both belong in the report. [11]

A separate 2025 mouse study found propranolol-associated reduction in CCR2-positive monocytes and cytotoxic CD4 T-cell-dependent anti-metastatic activity, with anti-CTLA-4 combination activity. Effects were context-specific; tumour MHC class II expression mattered. These are not human checkpoint-combination efficacy data, and do not mean reducing every myeloid population is beneficial. [20]

5H. Nerve-to-cancer mitochondrial transfer

Hoover et al. used nerve–cancer co-cultures, mitochondrial labelling, functional rescue and MitoTRACER lineage tracing to show that cancer cells can acquire functional neuronal mitochondria and that recipient descendants were enriched at metastatic sites. Human prostate tissue showed greater mitochondrial load near nerves; botulinum-neurotoxin-mediated denervation reduced that load. Cell-contact and nanotube experiments supported a physical transfer route. [19]

6. Anticancer combinations and sequencing

Combination evidence must be partner-, cancer- and schedule-specific. Formal synergy depends on the experimental model; a stronger effect than either drug alone is not sufficient. Increasing an effect on tumour cells can also increase toxicity in healthy tissues.

Treatment timing is an evidence question

Some experiments gave propranolol before a defined stressor; others started after implantation or combined it with ongoing systemic therapy. These are not interchangeable. The Dwivedi mouse regimen began seven days after inoculation, while the Campbell bone study exposed mice before and after circulating cancer cells were introduced. Neither creates a universal clinical lead-in. [13,15]

7. Research dosing, exposure and formulation

Absorption and exposure: at a glance

• Absorption: oral propranolol is almost completely absorbed, but extensive liver first-pass metabolism limits the amount reaching the general circulation. [2,3]

• First pass: the UK product information says the liver removes up to 90% of an oral dose; the archived US label gives average systemic availability around 25%. These are different summaries of variable exposure, not one fixed percentage for every person. [2,3]

• Peak: approximately 1–2 hours after a fasting immediate-release dose in the UK label; the US label gives a broader 1–4-hour range. Modified-release timing differs. [2,3]

• Elimination half-life: usually about 3–6 hours for immediate-release oral treatment; illness and formulation can change it. [2,3]

• Protein binding: about 80–95%. Total blood concentration is not the same as unbound concentration. [2,3]

• Formulation: do not assume once-daily modified-release gives identical exposure to the same total daily immediate-release dose. Conversion needs product-specific review.

• Food: Australian Inderal tablets may be taken before or after food. Keep administration consistent and follow the actual label; food can alter bioavailability. [1,3]

• Smoking and enzyme-inducing medicines can lower levels; inhibitors may raise them. Tell the team about starting or stopping smoking as well as medication changes. [3]

What the newer prostate paper adds to the exposure question

Alaskar reports mean plasma propranolol of 43 nM (0.043 micromolar) two hours after a 40 mg tablet in preliminary human work. Its laboratory signalling effects depended on local catecholamine concentration and competition, not a universal concentration threshold. In contrast, Dwivedi used 50 micromolar propranolol in cell pretreatment, and Pasquier's direct growth-inhibition IC50 was approximately 160 micromolar in transformed endothelial cells. These experiments test different effects; they cannot be merged into one "effective cancer concentration." [10,15,16]

8. Safety and practical monitoring

Common or important effects

Fatigue, reduced exercise tolerance, cold hands/feet, dizziness, gastrointestinal symptoms and sleep disturbance/nightmares can occur. Mood changes should be reviewed, but a history of depression is not automatically a universal contraindication; the transplant and melanoma trials used their own mental-health exclusions. New or worsening symptoms deserve assessment rather than automatic attribution to the drug. [1,2,9,17]

Fasting deserves its own warning

A practical prescriber-agreed plan

• Record the intended role and uncertain benefit, product/formulation, dose and all other medicines.

• Agree how often to measure BP and pulse, what symptoms require same-day review, and individual dose-hold instructions. Record measurements at consistent times after resting.

• Consider ECG, glucose, kidney/liver tests and electrolytes according to history, concurrent treatment and symptoms; not every patient needs every test on a fixed schedule.

• Seek written instructions for vomiting/poor intake, missed doses, procedures, fasting and trial entry. Do not double up missed doses.

• Do not self-escalate because BP/pulse seem tolerable: tolerance is not evidence of increased anticancer benefit.

• For continuing treatment, review fatigue, mobility/falls, respiratory symptoms, sleep, mood and nutrition—not just the pulse. [1,2,8,17]

Withdrawal, surgery and emergencies

Avoid abrupt discontinuation of regular propranolol, particularly with possible coronary disease. Australian information generally describes gradual reduction over about 8–14 days; other labels differ and the appropriate taper depends on the situation. Emergency adverse effects can require immediate withholding under medical direction, so "never stop abruptly" must not be interpreted as taking another dose during collapse or severe bronchospasm. [1–3]

Australian product information recommends continuing established maintenance beta-blockade perioperatively unless there is an indication to withdraw. Starting a new experimental perioperative course is a different decision. Tell the surgeon/anaesthetist; do not turn another country's conditional hold instruction into a universal 24-hour stop rule. [1,2]

9. Metabolism and interactions

How propranolol is metabolised

Propranolol undergoes extensive liver metabolism through ring hydroxylation (mainly CYP2D6), side-chain oxidation (mainly CYP1A2 with some CYP2D6) and direct glucuronidation. CYP2C19 also contributes. Most metabolites are eliminated in urine. P-glycoprotein is an efflux transporter, not a metabolic enzyme; the archived FDA label says it is not dose-limiting for intestinal absorption at usual therapeutic doses. [3]

Enzyme inhibitors can increase propranolol exposure and intensify slow pulse, low BP or other effects. Examples in the FDA pharmacology include fluoxetine/paroxetine, ciprofloxacin/fluvoxamine and fluconazole. Rifampicin and cigarette smoking can increase clearance. Sharing a CYP enzyme does not by itself prove a clinically important interaction; evaluate the actual drug pair, dose and patient. CYP2D6 genotype alone also does not reliably predict total propranolol clearance because several pathways contribute. [3]

Liver disease may increase bioavailability and unbound exposure; kidney disease can also alter pharmacokinetics despite hepatic metabolism. This is different from saying propranolol is cleared unchanged by the kidneys. Blood levels and tumour levels are not interchangeable. [1–3,16]

10. Supply, PBS and trial access

Australia: verified public product and PBS records

Australian Inderal information describes prescription-only (Schedule 4) propranolol hydrochloride tablets in 10 mg and 40 mg strengths. Product registration/listing does not establish pharmacy stock, individual suitability or oncology efficacy. [1]

Other countries and international sourcing

UK prescribing information supports the existence of prescription propranolol tablet products for established non-oncology indications. The US label cited here is archived pharmacology information and must not be used to claim current brand/strength availability. Local product records, pharmacy stock and import rules need country-specific confirmation. Research-grade material, another person's tablets or informal overseas clinic supply are not substitutes for lawful quality-assured prescribing. [2,3]

Clinical trials: evidence leads, not guaranteed places

Targeted public-record check dated 30 October 2026. Protocol details and an overall study listing do not guarantee that any particular site is currently enrolling. Where live status could not be retrieved reliably, the uncertainty is explicit. No currently open Australian propranolol cancer-treatment site was confirmed; that is not proof none exists. Hiller's published Australian research is not a present recruitment opportunity. [5,24–28]

Pharmacy and prescribing checklist

• Exact ingredient, strength, release form and whether splitting/crushing is permitted for that product.

• Prescriber responsibility and documented off-label purpose, uncertainty and reassessment point.

• Licensed pharmacy/manufacturer, batch traceability, expiry/storage and continuity of supply.

• Full interaction review, baseline BP/pulse and procedure/withdrawal instructions.

• If travelling: home-team handover, lawful cross-border supply and a plan if treatment is interrupted.

11. Clinician discussion and remaining evidence gaps

Questions to keep the discussion specific

• Which intended role is proposed: perioperative modulation, immune effects, bone-niche support, a chemotherapy pairing or another mechanism?

• Does the supporting experiment actually use propranolol, or a different blocker, denervation, receptor deletion or a mixed beta-blocker cohort?

• Is the endpoint a pathway marker, cancer-cell migration, tumour response, recurrence, survival or safety?

• What formulation/exposure is relevant, and what would count as a clinically meaningful benefit?

• What competing harms matter: asthma, low pulse/BP, fasting, falls, organ dysfunction or interactions?

• Who will coordinate the oncology, pharmacy and anaesthesia plan, and when will it be reviewed?

What remains unresolved

• A direct propranolol experiment measuring neuronal mitochondrial transfer, rather than inference across different pathways.

• Adequately powered independent randomised recurrence/survival trials and full publication of ongoing studies.

• Human unbound and intratumoural exposure, target engagement and validated selection/response biomarkers.

• Specific modern chemotherapy, radiotherapy, endocrine and targeted-therapy pairings, with dose/sequence and normal-tissue effects.

• Long-term safety/benefit in representative cancer populations, beyond selected short perioperative or early-phase studies.

• Live recruitment/site confirmation, especially Australia, and live supply/modified-release access; no verified Therapeutic Guidelines anticancer recommendation.

Core summary for linked library pages

Sources and further reading

Full reference entries below can be copied into the library. Numerical citations in the body refer to this list. Uploaded PDF filenames are working research inputs, not separate independent studies. All web/product/trial checks were made for this version on 30 October 2026; an access date is not a guarantee that every status was retrievable or current.

1. Australian Product Information and Consumer Medicine Information

Australian Product Information and Consumer Medicine Information. INDERAL (propranolol hydrochloride), 10 mg and 40 mg tablets. PI/CMI hosted by the Australian Commission on Safety and Quality in Health Care; checked 30 October 2026.

https://www.safetyandquality.gov.au/medicine-finder/inderal

Australian indications, contraindications, food instructions, interactions, perioperative continuation and withdrawal precautions.

2. Electronic Medicines Compendium

Electronic Medicines Compendium. Propranolol 40 mg Tablet (Ipca Laboratories UK): Summary of Product Characteristics. Updated on emc 24 March 2026.

https://www.medicines.org.uk/emc/product/101996/smpc

Product-specific pharmacology, absorption, elimination, safety and interactions; instructions may differ from Australian products.

3. US Food and Drug Administration

US Food and Drug Administration. Inderal (propranolol hydrochloride) tablets prescribing information. Archived label, 2011.

https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/016418s080,016762s017,017683s008lbl.pdf

Detailed metabolic pathways, protein binding, enzyme interactions and hepatic/renal pharmacokinetics. Archived, not a claim of current US supply or latest prescribing instructions.

4. O'Logbon J, Tarantola L, Williams NR et al.

O'Logbon J, Tarantola L, Williams NR et al. Does propranolol have a role in cancer treatment? A systematic review of the epidemiological and clinical trial literature on beta-blockers. Journal of Cancer Research and Clinical Oncology. 2025;151:212. DOI: 10.1007/s00432-025-06262-2.

https://pmc.ncbi.nlm.nih.gov/articles/PMC12255574/

Review of 31 publications (7 classified as randomised/clinical trial reports and 24 reviews/meta-analyses), with searches to July 2024. These are not 31 independent trials; some trial-related analyses are observational.

5. Hiller JG, Cole SW, Crone EM et al.

Hiller JG, Cole SW, Crone EM et al. Preoperative β-Blockade with Propranolol Reduces Biomarkers of Metastasis in Breast Cancer: A Phase II Randomized Trial. Clinical Cancer Research. 2020;26(8):1803–1811. DOI: 10.1158/1078-0432.CCR-19-2641.

https://pubmed.ncbi.nlm.nih.gov/31754048/

60-patient, placebo-controlled biomarker trial; not proof of recurrence or survival benefit.

6. Shaashua L, Shabat-Simon M, Haldar R et al.

Shaashua L, Shabat-Simon M, Haldar R et al. Perioperative COX-2 and β-Adrenergic Blockade Improves Metastatic Biomarkers in Breast Cancer Patients in a Phase-II Randomized Trial. Clinical Cancer Research. 2017;23(16):4651–4661.

https://aacrjournals.org/clincancerres/article/23/16/4651/80152/Perioperative-COX-2-and-Adrenergic-Blockade

38-patient propranolol–etodolac biomarker trial. Related publications from this cohort should not be counted as independent trials.

7. Ricon-Becker I, Haldar R, Simon MS et al.

Ricon-Becker I, Haldar R, Simon MS et al. Effect of perioperative COX-2 and beta-adrenergic inhibition on 5-year disease-free-survival in colorectal cancer: A pilot randomized controlled Colorectal Metastasis PreventIon Trial (COMPIT). European Journal of Surgical Oncology. 2023;49:655–661.

https://cris.tau.ac.il/en/publications/effect-of-perioperative-cox-2-and-beta-adrenergic-inhibition-on-5/

34-patient trial; five-year recurrence counts 2/16 versus 9/18. A corrigendum exists; see the later pooled report for updated follow-up. Publication details and abstract verified through the institutional record, not a fresh complete extraction of the correction.

8. Sakis N, Sorski L, Asraf E et al.

Sakis N, Sorski L, Asraf E et al. Favorable safety outcomes of a perioperative propranolol and etodolac regimen in cancer patients in four randomized controlled trials. Frontiers in Pharmacology. 2026;17:1823113. DOI: 10.3389/fphar.2026.1823113.

https://pmc.ncbi.nlm.nih.gov/articles/PMC13136142/

Pooled safety data from 148 patients; two completed and two ongoing trial cohorts. Exploratory colorectal follow-up is not a new independent efficacy trial.

9. Gandhi S, Pandey MR, Attwood KM et al.

Gandhi S, Pandey MR, Attwood KM et al. Phase I Clinical Trial of Combination Propranolol and Pembrolizumab in Locally Advanced and Metastatic Melanoma: Safety, Tolerability, and Preliminary Evidence of Antitumor Activity. Clinical Cancer Research. 2021;27(1):87–95. DOI: 10.1158/1078-0432.CCR-20-2381.

https://pmc.ncbi.nlm.nih.gov/articles/PMC7785669/

Nine-patient, uncontrolled dose-finding study; seven objective responses, all partial responses in the reported patient table.

10. Pasquier E, André N, Street J et al.

Pasquier E, André N, Street J et al. Effective Management of Advanced Angiosarcoma by the Synergistic Combination of Propranolol and Vinblastine-based Metronomic Chemotherapy: A Bench to Bedside Study. EBioMedicine. 2016;6:87–95. DOI: 10.1016/j.ebiom.2016.02.026.

https://pmc.ncbi.nlm.nih.gov/articles/PMC4856748/

Formal laboratory interaction studies and an uncontrolled seven-patient combination series. Maintenance and other treatments complicate attribution.

11. Embaby A, Heinhuis KM, IJzerman NS et al.

Embaby A, Heinhuis KM, IJzerman NS et al. Propranolol monotherapy in angiosarcoma – A window-of-opportunity study (PropAngio). European Journal of Cancer. 2024;202:113974.

https://www.sciencedirect.com/science/article/pii/S0959804924001308

14-patient monotherapy study; 2 clinical responses did not meet the prespecified efficacy criterion. Abstract/repository results verified; full-paper extraction remains incomplete.

12. Renz BW, Takahashi R, Tanaka T et al.

Renz BW, Takahashi R, Tanaka T et al. β2 Adrenergic-Neurotrophin Feedforward Loop Promotes Pancreatic Cancer. Cancer Cell. 2018;33(1):75–90.e7. DOI: 10.1016/j.ccell.2017.11.007.

https://pmc.ncbi.nlm.nih.gov/articles/PMC5760435/

Uploaded author manuscript extracted. Propranolol cell/organoid findings, selective ICI 118,551 mouse experiments and mixed non-selective beta-blocker observational data are kept separate.

13. Campbell JP, Karolak MR, Ma Y et al.

Campbell JP, Karolak MR, Ma Y et al. Stimulation of Host Bone Marrow Stromal Cells by Sympathetic Nerves Promotes Breast Cancer Bone Metastasis in Mice. PLoS Biology. 2012;10(7):e1001363. DOI: 10.1371/journal.pbio.1001363.

https://pmc.ncbi.nlm.nih.gov/articles/PMC3398959/

Uploaded main paper extracted. Drinking-water propranolol reduced restraint-stress-associated bone colonisation; no significant benefit in unstressed controls. Supplementary descriptions read, separate supplementary images not comprehensively extracted.

14. Magnon C, Hall SJ, Lin J et al.

Magnon C, Hall SJ, Lin J et al. Autonomic Nerve Development Contributes to Prostate Cancer Progression. Science. 2013;341(6142):1236361. DOI: 10.1126/science.1236361.

https://doi.org/10.1126/science.1236361

Uploaded main paper extracted. Denervation and β2/β3 receptor deletion are not propranolol treatment. The muscarinic pathway and its mouse survival findings are distinct.

15. Dwivedi S, Bautista M, Shrestha S et al.

Dwivedi S, Bautista M, Shrestha S et al. Sympathetic signaling facilitates progression of neuroendocrine prostate cancer. Cell Death Discovery. 2021;7:364. DOI: 10.1038/s41420-021-00752-1.

https://www.nature.com/articles/s41420-021-00752-1

Uploaded main paper extracted. High noradrenaline/propranolol concentrations in cells and four animals per group limit translation; no propranolol-only animal arm.

16. Alaskar A, Abdulraqeb Ali A, Hassan S et al.

Alaskar A, Abdulraqeb Ali A, Hassan S et al. Inhibition of signaling downstream of beta-2 adrenoceptor by propranolol in prostate cancer cells. The Prostate. 2023;83:237–245. DOI: 10.1002/pros.24455.

https://pmc.ncbi.nlm.nih.gov/articles/PMC10100053/

Uploaded primary paper extracted. Cell signalling, acute mouse prostate response and a preliminary human plasma-exposure observation; not a patient outcome trial.

17. Knight JM, Rizzo JD, Hari P et al.

Knight JM, Rizzo JD, Hari P et al. Propranolol inhibits molecular risk markers in HCT recipients: a phase 2 randomized controlled biomarker trial. Blood Advances. 2020;4(3):467–476. DOI: 10.1182/bloodadvances.2019000765.

https://pmc.ncbi.nlm.nih.gov/articles/PMC7013267/

Uploaded original extracted. 25 randomised patients undergoing first autologous transplantation for myeloma; molecular effects significant, engraftment/infection differences not statistically significant.

18. Johnson AK, Lorimer EL, Szabo A et al.

Johnson AK, Lorimer EL, Szabo A et al. Rap1A, Rap1B, and β-Adrenergic Signaling in Autologous HCT: A Randomized Controlled Trial of Propranolol. Yale Journal of Biology and Medicine. 2022;95:45–56.

https://pmc.ncbi.nlm.nih.gov/articles/PMC8961707/

Uploaded original extracted. Correlative analysis of the same 25-patient trial, not an independent clinical trial; no significant treatment effect on measured Rap1 abundance or prenylation.

19. Hoover G, Gilbert S, Curley O et al.

Hoover G, Gilbert S, Curley O et al. Nerve-to-cancer transfer of mitochondria during cancer metastasis. Nature. 2025;644:252–262. DOI: 10.1038/s41586-025-09176-8.

https://pmc.ncbi.nlm.nih.gov/articles/PMC12328229/

Mitochondrial-transfer mechanism paper; denervation and nanotube-inhibition experiments are not propranolol efficacy evidence.

20. β-adrenergic signaling blockade attenuates metastasis through activation of cytotoxic CD4 T cells

β-adrenergic signaling blockade attenuates metastasis through activation of cytotoxic CD4 T cells. Nature Communications. 2025. DOI: 10.1038/s41467-025-65048-9.

https://www.nature.com/articles/s41467-025-65048-9

Mouse study of CCR2-positive monocytes, cytotoxic CD4 T cells and anti-CTLA-4 combination activity; not a clinical immune biomarker or human regimen.

21. Pharmaceutical Benefits Scheme — item 2565B

Pharmaceutical Benefits Scheme. Propranolol hydrochloride 10 mg tablets, 100: item 2565B. Checked 30 October 2026.

https://www.pbs.gov.au/medicine/item/2565B

General Schedule, no restrictions on this item page; listed brands APO-Propranolol, PROPRANOLOL-WGR, Deralin 10 and Inderal. Not a cancer efficacy endorsement.

22. Pharmaceutical Benefits Scheme — item 2566C

Pharmaceutical Benefits Scheme. Propranolol hydrochloride 40 mg tablets, 100: item 2566C. Checked 30 October 2026.

https://www.pbs.gov.au/medicine/item/2566C

Listed brands APO-Propranolol, PROPRANOLOL-WGR, Deralin 40 and Inderal; stock and cost need pharmacy confirmation.

23. Pharmaceutical Benefits Scheme — item 13386M

Pharmaceutical Benefits Scheme. Propranolol hydrochloride 10 mg tablets, 100: item 13386M. Checked 30 October 2026.

https://www.pbs.gov.au/medicine/item/13386M

Separate larger-quantity listing with a stable-condition restriction; do not confuse item-specific conditions.

24. National Cancer Institute — NCT03384836

National Cancer Institute. Propranolol hydrochloride and pembrolizumab in unresectable stage IIIC–IV melanoma; NCT03384836 / NCI-2017-02210. Checked 30 October 2026.

https://www.cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2017-02210

NCI lists temporarily closed to accrual; not a confirmed open recruitment opportunity.

25. ClinicalTrials.gov — NCT03919461

ClinicalTrials.gov. Colorectal Metastasis Prevention International Trial 2; NCT03919461.

https://clinicaltrials.gov/study/NCT03919461

2026 primary report [8] identifies this as an ongoing Israeli trial; live registry status did not extract reliably. Site-level enrolment must be confirmed.

26. ClinicalTrials.gov — IMPULS, NCT06145074

ClinicalTrials.gov. IMPULS: Examining Safety, Efficacy and Feasibility of Preoperative Propranolol in Patients With PDAC; NCT06145074. Checked 30 October 2026.

https://clinicaltrials.gov/study/NCT06145074

Protocol and Copenhagen/Køge Danish locations verified. Current site-level recruitment not conclusively verified in the retrieved registry text.

27. ClinicalTrials.gov — PROPANE, NCT05961761

ClinicalTrials.gov. PROPANE: Propranolol and Pembrolizumab in Advanced Soft Tissue Sarcoma Patients; NCT05961761. Checked 30 October 2026.

https://clinicaltrials.gov/study/NCT05961761

Protocol and Denmark/Norway/Sweden locations verified. Study existence is not confirmation that every site is currently enrolling.

28. Australian Clinical Trials

Australian Clinical Trials. Find a clinical trial.

https://www.australianclinicaltrials.gov.au/about/find

Australian search route; no currently open Australian propranolol cancer-treatment site was confirmed by this targeted check.

29. Drugs.com Drug Interaction Checker

Drugs.com. Drug Interaction Checker.

https://www.drugs.com/drug_interactions.html

Free screening tool; not a substitute for a full oncology-pharmacist review.

30. Medscape Drug Interaction Checker

Medscape. Drug Interaction Checker.

https://reference.medscape.com/drug-interactionchecker

Free screening tool for prescription and non-prescription medicines and selected supplements.

31. NICE British National Formulary — Propranolol interactions

NICE British National Formulary. Propranolol interactions.

https://bnf.nice.org.uk/interactions/propranolol/

Includes predicted increased hypotension risk with dipyridamole.