The COC Protocol™ and Blood Cancer
Evaluating complex scientific articles and technical literature can be a daunting task. Our search of the literature has retrieved over 60 articles which detail and discuss the potentially beneficial effects of the COC protocol medications in blood cancers, (i.e. leukaemia, lymphoma, and myeloma).
In summary, there are three key points to consider:
- A large number of laboratory studies show that each of the COC protocol medications can
directly attack and help disable or kill blood cancer cells.
- Patients with blood cancer may benefit from taking the COC protocol alongside their
standard treatments. Many studies show that the particular medications used in the COC
protocol could help reduce resistance and improve the effectiveness of chemotherapy and other treatments.
- This evidence is very encouraging and further studies are needed to determine exactly how,and who, the COC protocol medications may help. Our specialist clinicians can assist you in deciding whether you could benefit from taking the COC protocol. Contact the Care Oncology Clinic on 800-392-1353 or submit a form to Learn More.
Statins have been widely prescribed for decades, and a large number of population studies (ie, studies which simply observe what happens to a defined group of people) provide evidence suggesting that statins may provide anticancer benefits for some people. These studies consistently seem to show that statin use can reduce the risk of developing any blood cancer (Yi et al., 2014); including lymphoma (Cerhan et al., 2007; Cho et al., 2015; Fortuny et al., 2006; Wallace et al., 2013; Ye et al., 2017), leukaemia (Pradelli et al., 2015), and multiple myeloma (Chiu et al., 2015; Epstein et al., 2017). Some studies also directly link statins to improved survival in blood cancer patients (although this evidence is more mixed) (Brånvall et al.; Ennishi et al., 2010; Sanfilippo et al., 2016).
This ‘observational’ evidence is supported by many laboratory studies, which show that some types of statin can actively target and damage blood cancer cells (Burke and Kukoly, 2008; Clutterbuck et al., 1998; Crosbie et al., 2013; Dimitroulakos et al., 2000; Matar et al., 1999; Qi et al., 2013; Sassano et al., 2007), and these findings in turn are supported by some early studies in patients.
For example, in one case study from 2001, lovastatin was given to a 72 year old patient with
relapsed acute myeloid leukaemia who did not want further induction therapy. The researchers found that the patient’s cells grown in the lab were sensitive to lovastatin, a statin similar to atorvastatin, and lovastatin was offered to the patient.
Lovastatin appeared to control the patient’s leukemic blast cells, and the authors reported that ‘this case illustrates the potential for lovastatin to provide a novel means of controlling leukemic cell growth in acute myeloid leukaemia patients (Minden et al., 2001).
High cholesterol levels in and around cancer cells can help them thrive and survive attack by anticancer treatments (Codini et al., 2016; Kuzu et al., 2016). Lab studies show that statins (which reduce cholesterol levels) can help keep blood cancer cells sensitive to chemotherapy and other treatments, and reduce resistance to these drugs (Lee et al., 2018; Li et al., 2003). Patient studies are now also beginning to support this. A Phase 1 study where patients with acute myeloid leukaemia were given increasing doses of pravastatin alongside a standard chemotherapy regimen had encouraging results, particularly in newly diagnosed patients with unfavourable prognosis due to the molecular makeup of their cancer. A total of 80% of these patients achieved a complete response, compared to just 40% for similar patients used as historical controls who had only a standard chemotherapy regimen (Kornblau et al., 2007).
A subsequent Phase 2 study in patients with relapsed acute myeloid leukaemia also achieved good results, with 75% of patients achieving an adequate response (Advani et al., 2014). A second Phase 2 trial in patients with untreated acute myeloid leukaemia and high-risk myelodysplastic syndrome was stopped early, as although results were still encouraging, they were unlikely to achieve a predefined level of success specified by researchers as an acceptable level of effectiveness (Shadman et al., 2015). Reasons for this are unclear and could be to do with patient subset, or trial methodology. Further, larger trials are ongoing .
Early-stage clinical trials in multiple myeloma have also shown positive results. In one small trial of 6 patients with refractory (ie treatment resistant) lymphoma, cancer resistance to standard treatments of bortezomib or bendamustine was reduced when simvastatin was added alongside (Schmidmaier et al., 2007). In another trial with 91 patients with relapsed or refractory multiple myeloma who were being treated with stem cell transplantation therapy, those who were treated with lovastatin alongside thalidomide and dexamethasone (49 patients) had improved responses and better survival compared to those who were given only thalidomide and dexamethasone without lovastatin (Hus et al., 2011). Subsequent studies in the lab showed that a combination of thalidomide and lovastatin was more toxic to cancer cells than either one alone, underlining the importance and potential benefits of using statins as an adjuvant therapy alongside standard treatments.
Despite the benefits, it is still important these medicines are given by specialists who can tailor dosages and regimens to each individual patient and their situation. For example, two small early stage trials in heavily pretreated patients with myeloma found that high doses of a statin may not be beneficial for some patients (Sondergaard et al., 2009; van der Spek et al., 2008).
Some large scale population studies indicate that taking metformin may help patients with blood cancers (Alkhatib et al., 2017; Wu et al., 2014). These studies also suggest that standard anticancer therapies may sometimes be more effective in patients with blood cancer who are taking metformin. For example, in one population study of patients with diffuse large B-cell lymphoma who were being treated with standard rituximab-based chemo-immunotherapy, diabetic patients who were also taking metformin had a longer time before their lymphoma progressed compared to nondiabetic patients and diabetic patients on other glucose lowering medications (Singh et al., 2013). Further investigations in the lab found that metformin is more effective at killing lymphoma cells sensitive to rituximab, but not those resistant to rituximab (Singh et al., 2013).
This finding might explain some of the differences in the effects of metformin reported in lymphoma patients being treated with rituximab (Hicks et al., 2017; Koo et al., 2011).
In a different population study in patients with multiple myeloma who had undergone stem cell transplant, metformin use was associated with a better response to stem cell transplant and a longer time until disease progression (Duma et al., 2017).
Various lab studies support these clinical findings. Many studies have found that metformin blocks growth and induces death in a number of lymphoma and myeloma cell types grown in the lab or taken from patients (Gu et al., 2015; Rosilio et al., 2013; Shi et al., 2012; Zi et al., 2015). Other studies have also found that the metabolic and molecular changes induced by metformin in lymphoma and myeloma cells help to improve the potency of anticancer treatments (Chukkapalli et al., 2018; Jagannathan et al., 2015; Patel et al., 2015; Zi et al., 2015).
Lab studies also suggest that metformin can benefit patients with leukaemia, both by directly acting on cancer cells, and by helping to lower high blood glucose levels, which are sometimes associated with treatment of leukaemia (Rosilio et al., 2014; Wang and Wetzler, 2015). This mode-of-action evidence shows that metformin can target, block growth, and destroy leukaemia cells through similar anti-metabolic and molecular mechanisms as it uses to damage lymphoma and myeloma cells (Kirito, 2013; Rodríguez-Lirio et al., 2015). It may also have the power to improve the effectiveness of other therapies used to treat leukaemia (Sabnis et al., 2016; Velez et al., 2016; Yi et al., 2017). These effects appear wide ranging across a number of different types of leukaemia; one study found that metformin was able to block oxygen uptake in 6 different types of leukaemia cell (Scotland et al., 2010).
Lab studies from as far back as 1985 suggested that doxycycline could stop tumour growth and eradicate tumours in rats with leukaemia (van den Bogert et al., 1985). Later studies which have since delved deeper into the mode-of-action of doxycycline and other tetracyclines have found doxycycline can target blood cancer cells in a myriad of different ways, over and above the traditional anti-bacterial and anti-inflammatory effects (Bahrami et al., 2012; Ferreri et al., 2006).
In one clinical trial where doxycycline was shown to help patients with a type of MALT lymphoma associated with certain bacterial infections, researchers initially believed the beneficial effects of doxycycline in this context was mostly down to its antibiotic, bacteria-eradicating properties (Ferreri et al., 2006). But growing evidence suggests that tetracyclines, and specifically doxycycline, are doing more than that. Numerous studies in the lab have now shown that doxycycline can directly damage, kill, or initiate processes which can lead to death (ie apoptosis) in a number of different types of cancer, including blood cancers (Alexander-Savino et al., 2016; Bahrami et al., 2012; Lamb et al., 2015; Pulvino et al., 2015; Song et al., 2014; Wang et al., 2015).
Intriguingly, a recent case study in a patient with B-cell lymphoma linked to a bacterial infection found that the patient’s lymphoma activity (which was being treated with chemotherapy, doxycycline, and hydroxychloroquine) aligned with their blood levels of doxycycline, and relapsed when doxycycline was stopped (Melenotte and Raoult, 2017). The authors state that this phenomenon emphasizes the ‘pro-apoptotic’ benefits of doxycycline. Clinical research is ongoing to establish just how and when doxycycline use can benefit patients with blood cancers.
Scientific interest in mebendazole as a potential anticancer treatment is relatively new, and is mostly based on promising mechanistic studies and compelling reports from case studies in cancer patients (Nygren and Larsson, 2014; Pantziarka et al., 2014).
Emerging evidence also suggests that mebendazole may have particularly high levels of activity against blood cancers. This is all down to how mebendazole works. Mebendazole is thought to kill cancer cells by disrupting special structures inside the cell, called microtubules. Vincristine, a chemotherapy treatment often used to treat leukaemia, lymphoma, and myeloma, works in a similar way. These mechanistic similarities, combined with mebendazole’s relatively low levels of side effects and good safety record has led to suggestions that mebendazole could actually be used to replace vincristine for treatment of some cancers (De Witt et al., 2017). Numerous clinical trials are now underway to investigate this possibility.
In addition, two separate large scale screening studies have also independently picked up the potential potency of mebendazole against leukaemia (Matchett et al., 2016; Nygren et al., 2013). In one of these studies (Nygren et al., 2013), the leukaemia panel was the most sensitive to mebendazole out of all cancer types tested. Both screening studies then went on to show that mebendazole can potently and selectively target animal and human leukaemia cells in the lab. Flubendazole, which is from the same family as mebendazole and works in a similar way, has also been shown to kill leukaemia and myeloma cells in the lab (Spagnuolo et al., 2010).
Purpose of this article
This article is an overview of some of the scientific and medical published literature concerning the medications which comprise the patented Care Oncology protocol. Care has been taken to select relevant articles supporting the off-label use of these medicines in a clinical setting for the adjunct treatment of cancer. This article does not purport to be a comprehensive review of all the evidence, nor does it capture all of the potential side-effects of such treatment.
This article is for information purposes only and it does NOT constitute medical advice. The
medicines discussed herein are available on prescription-only and should not be taken without consultation with your doctor or other professional healthcare provider. Care Oncology doctors will discuss the suitability of these medicines with you and will liaise with your doctor or oncologist to discuss their suitability for you.
You must NOT rely on the information in this article as an alternative to medical advice from your doctor or other professional healthcare provider. If you have any specific questions about any medical matter you should consult your doctor or other professional healthcare provider. If you think you may be suffering from any medical condition you should seek immediate medical attention. You should never delay seeking medical advice, disregard medical advice, or discontinue medical treatment because of information contained in this article.
The copyright in this article is owned by Health Clinics LLC and its licensors.
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