COC Protocol Medications - information sheets

METFORMIN 

Metformin is a drug which is used for patients with type two diabetes. The medicine reduces the amount of sugar made by the liver, limits the amount of sugar absorbed into the body from the diet, and makes insulin receptors more sensitive (helping the body respond better to its own insulin). All of these effects cause a decrease in blood sugar levels. 

Metformin may additionally be useful for patients with cancer because the cancer cells become ‘sugar hungry’. Energy for the cancer can come from the processing of glucose metabolites and in order for the cancer to achieve its requirements, the cells create more receptors (GLUT1) to bring in the glucose. Metformin reduces cancer's energy supply by reducing the amount of sugar produced. Metformin still allows glucose into normal cells with through a different receptor which takes glucose into healthy cells and helps lower circulating blood sugar levels.    

SIDE EFFECTS 

Below is an outline of the most common side effects. For a full list, including those that are rare, please consult the patient information leaflet inside your Metformin medicine packaging. 

Abdominal or stomach discomfort               

Cough or hoarseness 

Decreased appetite                                     

Diarrhoea 

Fast or shallow breathing                            

Fever or chills 

General feeling of discomfort                       

Lower back or side pain 

Muscle pain or cramping                             

Painful or difficult urination 

THINGS TO REMEMBER

  • Do not take metformin on the day of any scan with contrast and for 48 hours after the scan. The contrast material may affect how your kidneys clear metformin from your body (new guidelines mean that some NHS hospitals no longer require patients who take Metformin to stop their medication, but this can vary between hospitals and we err on the side of caution on this point)
  • If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double dose.
  • Alcohol -- you can drink alcohol while taking metformin, but it is best to only drink occasionally and no more than two units a day. Drinking more can increase the risk of severe low blood sugar. 
  • Metformin does not exert a hypoglycaemic action in non-diabetic subjects unless given in overdose. 
  • Do not take metformin on the morning of surgery or planned procedures involving anaesthesia.  

REFERENCES 

British Medical Association and the Royal Pharmaceutical Society of Great Britain (2013) British National Formulary, BMJ Publishing Group, 66th Edition, pp 454-455. 

Gallagher. E and LeRoith. D (2011) Diabetes, cancer, and metformin: connections of metabolism and cell proliferation, Annals of the New York Academy and Sciences, pp 64-68. 

Yin. M, Zhou. J, Gorak. E and Quddus. F (2013) A Systematic Review and Meta-Analysis Metformin Is Associated With Survival Benefit in Cancer Patients with Concurrent Type 2 Diabetes, The Oncologist, 18(11).


ATORVASTATIN 

Atorvastatin is a drug that decreases the production of LDL cholesterol by blocking the action of the enzyme in the liver (called HMG-CoA reductase) that is responsible for its production. Cancer cells have elevated LDL receptors which take the cholesterol into the cells, consequently providing the cancer cells with the necessary lipids to reproduce and grow. The cancer can be affected by reducing the level of LDLs which impacts the production, proteins and cell membranes required for the cancer’s daughter cells. 

SIDE EFFECTS 

Each person reacts differently to any medication and a large proportion of patients experience no side effects whilst taking Atorvastatin. Below is an outline of the most common side effects. For a full list, including those that are rare, please consult the patient information leaflet inside your Atorvastatin medicine packaging. 

Nausea and Vomiting                                  

Diarrhoea 

Digestive problems                                     

Loss of Appetite                                          

Muscle Aches and Pains 

Nose Bleeds                                               

Headaches 

This is not an exhaustive list of potential side effects so you should carefully read the information leaflet that comes with your medication. If you find certain side effects particularly troublesome you should call the clinic and your dose may need to be adjusted or you may need a different type of statin. While side effects can sometimes be troublesome, it is important to also appreciate the very real benefits statins can provide. 

THINGS TO REMEMBER 

  • Atorvastatin may interact with other medicines; ensure you inform your doctor of all the medications you are taking including complementary therapies, vitamins and herbal drugs. 
  • If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double dose.

REFERENCES 

Gallagher. J (2013) Cholesterol fuels breast cancer: http://www.bbc.co.uk/news/health-25142026

Singh. S and Singh. P (2013) Statin a day keeps cancer at bay, World Journal of Clinical Oncology, 4(2), 43-46. 

Hindler. K, Cleeland. C, Rivera. E and Collard. C (2006) The Role of Statins in Cancer Therapy, The Oncologist, (11) 306–315. 

British Medical Association and the Royal Pharmaceutical Society of Great Britain (2013) British National Formulary, BMJ Publishing Group, 66th Edition, pp168-170. 


DOXYCYCLINE

Doxycycline is a broad-spectrum antibiotic part of a group of drugs called Tetracyclines. Doxycycline works by interfering with the ability of bacteria to produce proteins that are critical to them. Without these proteins the bacteria cannot grow and the Doxycycline therefore stops the spread of the infection and the remaining bacteria eventually die. However, scientific data suggests that this group of medications can additionally benefit patients suffering from cancer by interfering with the cell growth cycle by entering the cancer cells, disturbing their energy source and consequently slowing the development of cancer.  

SIDE EFFECTS  

Each person reacts differently to any medication and a large proportion of patients experience no side effects whilst taking Doxycycline. Below is an outline of the most common side effects. For a full list, including those that are rare, please consult the patient information leaflet inside your Doxycycline medicine packaging. 

Yeast infections                                                

Throat irritation 

Indigestion                                                        

Abdominal pain 

Diarrhoea 

Loss of appetite                                                

Feeling sick/being sick                                                        

Skin may become more sensitive to sunlight 

THINGS TO REMEMBER 

  • Using antibiotics in this way does not prevent all infections, so it is still important to use the same precautions as when you are not taking prophylactic antibiotics. 
  • If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double dose.
  • If at any time, your GP or oncologist prescribes a course of treatment antibiotics and this coincides with a period during which you are taking doxycycline, please contact Care Oncology Clinic for further advice. If you are taking mebendazole during this period, it is ok to combine the treatment antibiotic and mebendazole.  
  • Do not take indigestion remedies, or supplements containing iron, magnesium, or zinc at the same time as you take doxycycline. If you need to take these preparations, make sure you leave at least two hours before or after taking doxycycline before you have them. 
  • Due to the fact doxycycline can make skin more sensitive to sunlight, when taking it, try to stay out of direct sunlight, wear protective clothing and apply sunblock as appropriate.  

REFERENCES 

Inhibition of DNA-PK, ability to target cancer stem cells, radio-sensitisation of cancer cells: http://www.ncbi.nlm.nih.gov/pubmed/26087309http://www.ncbi.nlm.nih.gov/pubmed/25625193

Inhibition of matrix metalloproteinases (MMPs); treatment of metastasis: http://www.ncbi.nlm.nih.gov/pubmed/14597870


MEBENDAZOLE (Vermox)  

Mebendazole is an antiparasitic medication used to treat certain types of worm infestations of the gut and is part of a group of drugs called Anthelmintics. Mebendazole works by preventing the worms from being able to absorb the sugars that are essential for their survival and scientific data suggests it could do the same to your cancer.  

In cancer, studies have also shown that mebendazole inhibits tubulin formation inducing mitotic arrest which in turn induces apoptosis (cell death) in cancer cells.  

In addition, mebendazole inhibits pyruvate kinase, a key enzyme in the glycolytic pathway which is dominant in cancer cells. 

SIDE EFFECTS  

Each person reacts differently to any medication and a large proportion of patients experience no side effects whilst taking Mebendazole. Below is an outline of the most common side effects. For a full list, including those that are rare, please consult the patient information leaflet inside your Mebendazole (Vermox) medicine packaging. 

Stomach pain                                             

Diarrhoea 

Flatulence (wind)                                        

Stomach discomfort 

THINGS TO REMEMBER 

  • Cimetidine may decrease the breakdown of mebendazole by the liver and so increase the amount of mebendazole in the blood.
  • The manufacturer recommends that mebendazole should not be used in combination with the antibiotic metronidazole
  • If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double dose.

REFERENCES 

Inhibition of tubulin formation inducing mitotic arrest which in turn induces apoptosis in cancer cells: http://www.ncbi.nlm.nih.gov/pubmed/12479701http://www.ncbi.nlm.nih.gov/pubmed/2 1764822  

Inhibition of pyruvate kinase, a key enzyme in the glycolytic pathway of glycolysis which is dominant in cancer cells:  http://www.ncbi.nlm.nih.gov/pubmed/8010090.   

Macmillan Cancer Support – Advice on avoiding infection: http://www.macmillan.org.uk/information-and-support/coping/side-effects-andsymptoms/other-side-effects/avoiding-infection.html