Research on use of statins in cancer

Our nurses have recently received several questions related to statins, one of the medications in the COC Protocol. The following section of our January 2021 newsletter discusses the research literature relating to statins in the context of cancer and addresses some issues raised by a particular journal paper some patients have enquired about.

Statin safety profile

Statins have a good and well understood safety profile in humans. Like all medicines, they may give rise to side effects in some patients, but most people tolerate them well and do not have any problems. Patients often express concerns about the possibility of statin-induced muscle pain, but the actual risk is about 5% or less compared with placebo (a pill that does not contain any medication). Incidence of liver adverse reactions is also quite rare, at less than 2%.

The fact some level of risk exists is precisely why Care Oncology checks bloodwork at baseline and at regular intervals, and monitors for possible side effects. Our team will adjust the dose of statin or pause it if we become aware of any concerns. And of course, we take the same approach with all the other COC protocol drugs too.

Care Oncology’s clinical experience with our patients to date is in line with the risk profile outlined above i.e. the vast majority can tolerate statins without any issues. Blood cell counts and organ function abnormalities are most frequently linked to chemotherapy and/or other conventional care treatments which carry a greater toxicity risk than any of the COC Protocol medications.

Research on use of statins in cancer

Very large numbers of cancer patients take both a statin and metformin for management of other long-term health conditions and need to remain on these drugs for the duration of their cancer treatment. Therefore, a great deal of accumulated safety data exists on their use alongside standard of care cancer therapies, spanning chemotherapy, hormone therapy, targeted therapy, and immunotherapy.

Numerous studies have also shown statins can help to improve the effectiveness of conventional cancer therapies such as chemotherapy and radiotherapy and may help reduce the development of resistance to standard treatments.

In addition, there is now emerging data on the potential for statins to exert protective effects on the heart in patients undergoing chemotherapy.

Due to the high numbers of cancer patients taking a statin for other health conditions, it has been possible to conduct large retrospective studies to explore their impact on cancer incidence and outcomes across different cancer types. These studies have been encouraging and therefore acted as a catalyst for further research, including a growing number of human trials.

Lipophilic statins

The overall data is particularly compelling on the beneficial effects of fat-soluble lipophilic statins in cancer, rather than water-soluble hydrophilic statins.  In addition, lipophilic statins cross the blood-brain barrier more readily.  Atorvastatin, simvastatin and pitavastatin are lipophilic statins, whereas rosuvastatin, pravastatin and fluvastatin are more hydrophilic. As a lipophilic statin, atorvastatin has been extensively explored in the context of cancer and has been generally shown to have superior anticancer effects at the cellular level compared to other less fat-soluble statins. It also has the most extensive safety database due its widespread use for its labelled indication, and allows for dose escalation (as tolerated) to the highest dose achievable.

The power of statins in combination with other medicines

Recent research has demonstrated the potential for enhanced benefit from statins alongside other off-label medicines. e.g. statin + metformin in prostate cancer and endometrial cancer, and statin + metformin + NSAID in lung cancer.

Such studies support the scientific approach at the core of Care Oncology, namely that multiple points of intervention are likely to be needed for a metabolically targeted therapy to have the potential to be truly effective. This is the reason we devised a coherent combination of medicines to address related mechanisms involved in cancer cell metabolism. In this way, the activity of each drug, when given in combination, can potentially produce a synergistic effect and agents do not interfere with or impede one another.

COC Protocol Medications – Mechanisms of action

Diagram of cell breaking down each part's capabilities

A word on contradictory/inconclusive studies

We chose the combination for the COC Protocol carefully – because of the wealth of data in cancer and the safety profile of the medicines separately, together and with standard of care therapies.

This level of safety and efficacy data does not exist for most other off-label medicines, particularly in a combination setting.

We believe it is important to assist our patients to assess different types of evidence and the likely significance of reported results. Fundamentally, our position is that limited pre-clinical data in isolation should be approached with caution – the pharma industry writes off billions of dollars annually in the quest to translate lab studies in rodents to relevant findings for safe and effective treatment of humans.

Recently, several patients have asked us to comment on this paper: Statins have biphasic effects on angiogenesis (Weis et al 2002)

In response to this, we would make the following points:

  • Since 2002 there has been a wealth of supportive published papers on the potential of statins in numerous cancers, especially as regards lipophilic statins (e.g. Atorvastatin) and including human clinical trials.
  • The study referenced is 18 years’ old and laboratory based, in mice. To use mouse body weight as a direct extrapolation to humans is simplistic and inaccurate and human dosing is never based on preclinical research. Without corroborating human data, it is not possible to draw firm conclusions on the possible effects of statins on angiogenesis or any other potential mechanisms relevant in an anticancer setting.

Doses of all medications in humans must be titrated to the individual to avoid toxicities. In the case of Atorvastatin, 40mg once a day is considered a potent therapeutic dose.

  • A common feature of contradictory or inconclusive studies is that frequently they do not research the drug in question alongside standard of care therapies and/or they consider it as a single agent rather than deployed as one component of a coherent metabolically targeted combination.
  • Some cancer research on single agent statin does suggest a greater potential for overall anticancer therapeutic benefit at higher doses, which is why we seek to establish patients at 40mg Atorvastatin daily wherever safe to do so, rather than prescribing a lower dose. Use of Atorvastatin also allows for the possibility of escalating further to 80g daily depending on tolerance, satisfactory lab values and consideration of standard of care therapies and other concomitant medication.

Where it is not a suitable for a patient to be on a 40mg daily dose, our clinicians may still consider a lower dose to be worthwhile, again keeping in mind the principle that the potential for therapeutic benefit is amplified by the combination of medicines.

  • It is key to remember that all the COC Protocol medicines have multi-faceted effects in cancer and that we are using them in combination with standard of care therapy and with each other. Both Mebendazole and Metformin also demonstrate the potential to inhibit angiogenesis.

Further information

Visit our website to read more about statins and the other COC Protocol medications in the context of specific cancer types – https://careoncology.com/ – Click on “COC – Select Cancer Types” from the homepage menu

Click here to read our research paper published in Frontiers which provides more detail on our approach and includes preliminary results for our Glioblastoma IV brain tumor cohort. https://www.frontiersin.org/articles/10.3389/fphar.2019.00681/full