You are on page 1of 17

Tomas Mann McLeod

Can Thalidomide be used to cure Myeloma cancer?


The Biological Problem
Myeloma is a cancer of the plasma cells produced in the bone marrow. Plasma cells are produced in the bone marrow, in order to replace old and worn plasma cells in the body in a controlled manor. If a person is diagnosed with Myeloma cancer however, the plasma cells are produced in an uncontrolled way causing them to become abnormal, these abnormal plasma cells are referred to as Myeloma cells. This is a problem for the sufferer of the cancer because the abnormal out of control plasma cells fill up the bone marrow and interferes with the production of standard white blood cells, red blood cells and platelets; all the components of blood. [1] The Myeloma cells then spread through the whole bone marrow structure. The large quantity of the plasma cells cause serious damage to the bone, it causes the bone to become thinner, leading to a lot of pain and in some cases Myeloma can cause the bone to fracture because of the over production of the Myeloma cells. The fracturing of the bone leads to another side effect; the bone fracture causes severe pain and limited use of the
This image has been used as it clearly illustrates the number of Myeloma cells in comparison to normal plasma cells. [3]

area supported by the bone.

The mutated form of the cell produces a large quantity of a single type of antibody called immunoglobulin. This antibody is ineffective with regards to fighting infection and reduces the production of other useful antibodies which make up the bodys immune system, thus making the sufferer more prone to infection as there are less of the antibodies to protect the body from harmful pathogens. There are many types of Myeloma cancer, the type of Myeloma cancer is defined by the type of the antibody (immunoglobulin) that it produces. In each different sufferer of the cancer one type of immunoglobulin is over produced, the five basic types are: A (found in mucous, tears and breast milk to break down pathogens), high levels of IgA also increase in some autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus (SLE), and in liver diseases, such as cirrhosis and long-term (chronic) hepatitis. [17] D (part of the B cell receptor, it activates basophils and mast cells) the effects are not fully understood, but it limits the amount of plasma cells that can turn into other immunoglobulins. [17] E (protects against parasitic worms that are responsible for

This image shows the different structures of immunoglobulins that could be produced.

Tomas Mann McLeod

allergic reactions), it limits the amount of plasma cells that can turn into other immunoglobulins. [17] M (may be attached to the surface of a B cell or secreted in the blood) ), it limits the amount of plasma cells that can turn into other immunoglobulins [17] G (secreted in the plasma cells in the blood and able to cross the placenta into the blood). If too much of this immunoglobulin is produced, more of it will cross the placenta which can cause damage to the growing foetus also long-term hepatitis, multiple sclerosis (MS), and some autoimmune diseases. [17]

The most common type of Myeloma cancer is IgG and the least is IgE. The different types refer to the different type of immunoglobulin produced. [1][4]

The main risk factors of Myeloma cancer are being 65 and over, (70% of all sufferers of Myeloma cancer are of age 65 and over). Additionally race is a large factor; Myeloma is twice as common in black people as white and Asians. Additionally being male also drastically increases the chances of Myeloma cancer. The cancer is the 17th most common cancer with 13 people being diagnosed in the UK alone every day. This image illustrates those that have higher risk
of being diagnosed with Myeloma cancer.

Myeloma cancer is a biological problem because it is the cause of around 2,700 people (around 1,400 men and around 1,300 women) died of myeloma in 2011 in the UK, thats more than 7 people every day. [15] In addition to this Myeloma cancer approximately 1% of cancer cases identified (Antitumor Activity of Thalidomide in Refractory Multiple Myeloma).

Tomas Mann McLeod

Biological Method
The use of the medication thalidomide is currently being tested as a treatment for Myeloma cancer, as well as other forms of cancer. Cancer requires a network of new blood vessels in order to spread. The cancer encourages this production of new vessels. [5] [14]

This image has been used as it demonstrates the form in which thalidomide comes. [6]

This diagram illustrates the way thalidomide stops angiogenesis (the physiological process through which new blood vessels form from pre-existing vessels en.wikipedia.org/wiki/Angiogenesis). Thalidomide works by stopping angiogenesis. It stops this by stopping the cell growth section of the diagram by limiting its oxygen supply

Thalidomide however stops the production of the new vessels; this type of drug that has this affect is called an angiogenesis inhibitor; it does this by altering or removing the chemicals that encourage this growth. The new vessels provide vital nutrients for the cancer including oxygen for the cancer to grow. Oxygen is vital for the growth of the vessel, as oxygen is needed for the respiration of the cells that make up the vessel. Hence, thalidomide then reduces the growth of the cancer by stopping the new vessels that provide the molecules cancerous plasma cells require to grow. [5] This method works by stopping the Myeloma cells spreading and thus limiting the cancer to very few cells which will eventually die out as they come to the end of the cell lifecycle. Thalidomide causes the number of Myeloma affected cells to decrease to a size so small (by cutting off their oxygen supply, stopping their growth), making the cancer cells ineffective even before they reach the end of the cell cycle. Therefore it stops the production of the uncontrolled plasma cells that produce the different types of myeloma cancer. The different forms of the Myeloma cancer do not affect the different treatments of the cancer; thalidomide can be used to treat all types of Myeloma cancer.

Tomas Mann McLeod

Thalidomide is given in a 50mg capsule and is taken alongside a chemotherapy drug at the same time, the Thalidomide is taken orally. It is administered as a nightly dose of 200mg, then the dose is increased by 200mg every two weeks for 6 weeks, therefore the final dose is 800mg per day. The treatment can last anywhere between 2-465 days. [14] Some types of chemotherapy for myeloma are tablets that you swallow. Others are a liquid given into your vein. Cancer research UK. A steroid drug is also taken if the sufferer is over 65and arent suitable for large doses of treatment with stem cell support, some steroids are taken as tablets. Dexamethasone, prednisolone and methylprednisolone are the steroid drugs most commonly used for myeloma and are taken in the form of an injection. Cancer research UK. All of which are other methods that work to cure Myeloma cancer.

Tomas Mann McLeod

Effectiveness of methodology

This table has been used as it illustrates the effectiveness of the treatments using survival rates. From the table it is clear to see that although there are 4,672 new cases per year, there are only 2,693 deaths, almost half. This data was collected after Thalidomide was being used as a treatment, enforcing the effectiveness of using Thalidomide.

The methods mentioned are proven to be effective, because now the use of recent biological methods have dramatically increased. The chances of surviving for longer than 5 years has more than tripled over the last 35 years; with thalidomide, chemotherapy and steroids being used as the main source of treatment it is proven to be successful, all of which have been developed, improved and used as treatments over this period. In addition to this it is proven that one in seven from England and Wales will survive for the cancer for 10 years plus (table above), this emphasises the successfulness of the treatments available for Myeloma as the majority of the sufferers of Myeloma are 75 and above, strongly suggesting that their death was caused by wear and tear rather than the cancer because the life expectancy in the UK is currently at 81 years of age. This statistic means that people diagnosed with Myeloma in England and Wales are 3 times more likely to survive for more than 10 years more than those diagnosed in the 1970s. The aim of the treatment is to limit the effects of the cancerous plasma cells and increase life expectancy. These statistics prove that the treatments of Myeloma cancer are successful.

Tomas Mann McLeod

This graph reinforces the successfulness of the new treatments available as the number of new cases of Myeloma cancer is increasing, yet deaths are falling. Following the pattern that the graph illustrates Myeloma mortality rate is set to decrease ever further. The graph illustrates that there is a 2:1 ratio of new cases to death rates. This is evident as the graph demonstrates that in 2010 there were 300,000 deaths due to Myeloma and 650,000 new incidents of Myeloma.

This graph was used as it shows the no. of deaths compared to new cases of Myeloma. [10]

This graph shows the relationship between thalidomide sales and mutations in children, the graph shows a clear distinct pattern, clearly showing that as more thalidomide was consumed, more offspring were affected.

Tomas Mann McLeod

Implications
Thalidomide was originally created and prescribed in Germany that was used as a hypnotic or as a sedative, shortly after it was used by pregnant women to prevent morning sickness and was sold as an over the counter drug. However, soon after in 1961 it became clear that the drug was the cause of mutations in the limbs of the offspring of the patients that used the drug. It first made doctors suspicious of the drug when many patients had damage in the nerves of their limbs after long term use. Thalidomide caused mutations of 10,000 children. This disaster was the cause of more vigorous drug testing. Despite the large number of mutated offspring, not all the children whose mothers took the drug were affected; only the ones that took the drug in the early stages of pregnancy. As well as the offspring however, the Myeloma sufferer can also suffer nerve ending issues, this is due to peripheral neuropathy (damage to nerves outside the central nervous). [11]

Ethical implications: Due to the history of the infamous drug, many would be sceptical with regards to the use of the drug medically because of its disastrous history. In addition if the sufferer of Myeloma cancer did happen to be pregnant during the course of their taking their medication there is a chance of their offspring expressing limb mutations. This would greatly decrease the quality of life of the offspring and the mother. This situation would arise the question should the mother take the medication if it puts her childs wellbeing at risk?

The devastating effects of thalidomide on the offspring can be seen here, both suffers have non-functional limbs

Outside the past of thalidomide, many could be against the use of thalidomide as a cure for Myeloma cancer due to the fact that it wouldve been tested on animals to see how successful the drug is. Many are ethically against this because of their morals, this opinion wouldve been drawn from the ethical framework of Rights and Duties as they feel it is their right to look after the animals. On the other hand people may be supportive of using thalidomide as despite animal testing, it saves the lives of many people which go on and make the world a better place, this would be categorised under maximising the good in the world.. However, this view would also be shared by someone looking in their own interest as they would be taking every option available to them in order to cure them of Myeloma cancer. Conversely,

This image was used because it shows the extent at which the drug affects the offspring.

Tomas Mann McLeod

someone living leading a virtuous life would most likely object the treatment as most religions are against the use of animal testing. Buddhism for example is against the use of animal testing as they value every creature equally, "True benevolence or compassion, extends itself through the whole of existence and sympathizes with the distress of every creature capable of sensation." - Joseph Addison (Buddhist). Economic implications: Myeloma cancer is an extremely costly condition that greatly sets the NHS back financially. A cancer sufferer on average costs the NHS 30,000 [13] in medication. Additionally the treatment has no guarantee of working, so in the eyes of the economy, that is 30,000 potentially wasted. In addition the health This image shows the amount of money the system is a public good supplied by the government spends on the NHS. government; it costs the public a lot of money in the form of taxes. Economically the NHS is there in order to cure those who arent working and get them into work as soon as possible, therefore the unemployed cancer sufferers are a financial burden on the UK economy. Furthermore, with the treaments of Myeloma cancer such as using thalidomide only cost the government more money. From the table it is clear that the cost of treating cancer is only increasing [12] . By 2021 the cost of treating cancer is estimated to cost the NHS 13,191 million, an increase of 65%, this is not a true reflection of the implications of the treatment as a previous graph illustrates that there are more numbers of new cases diagnosed. The average cost of a 28-capsule pack of 50mg Thalidomide costs 298.48. Therefore if the treatment were to last 465 days, it would cost 725,000 for the thalidomide treatment alone, making Myeloma cancer the most expensive cancer treatment. Economically many would argue that this money could be spent more wisely on education for example.

Tomas Mann McLeod

Disadvantages of method
As well as mutated offspring, thalidomide can also cause the following side effects: Risk of blood clotting: In Myeloma cancer, thalidomide works by clotting the blood cells that cause the cancer to grow, however as the drug is taken orally, it does not only affect the area around the bone marrow, therefore it can cause the blood to clot unwillingly. However in order to counter this blood thinning drugs can be taking alongside the thalidomide. The use of these blood thinning drugs lead to another disadvantage. The average cancer treatment cost 30,000 per person [12]; the use of thalidomide only increases this price by 750,000, with blood thinning drugs pushing this price up even further. This has a knock-oneffect. As this large sum of money is being used for one Myeloma sufferer, it means it cannot be used for someone else who is waiting for funding for a treatment under the NHS. Increased risk of illness and infections Thalidomide reduces the amount of white blood cells produced the way it works as explained under Biological method. This weakens the immune system as it is made up of white blood cells, as there is less, it is harder to locate and stop pathogens getting in and affecting the body. It can also cause breathlessness and tiredness because the bone marrow would limit the production of red blood cells, less oxygen can be picked up from the lungs through the haemoglobin in the red blood cells.

Advantages of method
As highlighted earlier the advantage of using thalidomide is that it can increase the life expectancy of Myeloma suffers. Despite being an effective method of treating those with Myeloma cancer it can also a cheaper method than other available alternatives if the prescribed treatment period is a matter of days. A capsule pack of 50mg capsules costs around 300 for 28 capsules and only 4 capsules are used per day in early treatment. Chemotherapy and radio therapy on the other hand cost 35,000, in addition to this radiotherapy is more dangerous than thalidomide, this is because radiotherapy causes damage to the bone in Myeloma sufferers which can cause bone fractures.

This image shows the magnitude of radiotherapy treatment in comparison to thalidomide as illustrated previously.

Radiotherapy sometimes slows down the cells in the bone marrow that produce your blood cells. This is more likely if you are having a large area of the body treated or if treatment is to the bones of your legs, chest, abdomen or pelvis. Cancer Research UK.

Tomas Mann McLeod

This graph shows the likelihood of the symptoms induced from radio therapy In addition to cost and the success rate of the cure of Myeloma cancer, thalidomide is prescribed in a tablet form, therefore it is orally which requires less hassle than chemotherapy and even more so than radiotherapy which costs the NHS millions in electricity and the equipment. Additionally the toxicity report of thalidomide is substantially milder than chemotherapy. This suggests that there are more risks of using chemotherapy in comparison to thalidomide. In addition to its success rate of a treatment for Myeloma cancer, it can also work if the sufferer has a relapsed or a treatment on its own if none of the other treatments have worked to cure the disease. This has been proven to work in 50% of patients, reinforcing its success of being a treatment. This has been proven as thalidomide being used in the treatment of Myeloma extended the life expectancy by an average of nine months longer than someone not receiving thalidomide in their Myeloma treatment.

10

Tomas Mann McLeod

Other Methods
Chemotherapy with steroids: Chemotherapy works by killing the cancer cells completely unlike thalidomide, it kills off the cancer cells by affecting the mitosis of the cells. It stops the replication of the cells by stopping the centrioles from creating the spindle used to pull the cell apart in anaphase and telophase, and mitosis is how all body tissues are made, by the replication of cells that have identical structure and function; cancer cells however This shows how chemotherapy can be given to a patient. divide at a much faster rate than tissue cells, [9] thus making chemotherapy a very effective method of stopping the production of new cancer cells. [7]. In Myeloma chemotherapy stops the reproduction of the plasma cells by altering the cells that are cancerous (they produce the immunoglobulin antibody) so it stops them being able to spread across the bone marrow by changing some of the genes in cancers chromosomes and limiting the production of other factors of the blood, causing them to decrease until theyre unrecognisable and will no longer multiply. Steroids are given as part of a cancer treatment. They are substances that are produced naturally by our bodies in the adrenal glands. It can also be produced outside of our bodies and be used as drugs. Steroids are used alongside chemotherapy in the treatment of Myeloma [2] as well as other forms of cancer [8]. It works by increasing the This image shows the different forms effects of the chemotherapy, which stops the mitosis of in which steroids are available in. the cells. Chemotherapy drugs are inserted into the blood supply. Steroid drugs are put into the blood supply also as the two need to work in sync to optimise its effectiveness. It also reduces the immune systems responses, so if the body rejects the chemotherapy then the steroids will decrease the rejection.

11

Tomas Mann McLeod

Radiotherapy
Radiotherapy works by exposing the body to large amounts of radiation, radiation is a form of energy that is carried by a wave of particles. This wave of particles alters the DNA cells that control the cell dividing genes in the nucleus of the cell. Therefore it works to cure Myeloma cancer by damaging the dividing gene in the multipotent cell nucleus. This results in the cancerous cells being unable to divide, limiting the effect of the cancer cells in the body. Eventually the cancer cells will die out when they reach the end of interphase in the cell cycle, meaning the sufferer would be cured of the cancer. [16] The effectiveness of exposing the body to radiation to stop cell growth mainly depends on which part of the cell cycle the cell is in. Radiation first affects the cells that are not in interphase because they are in the process of dividing because that cells life is nearly finished before it divides into two cells. As well as what stage the cell is in the cell cycle, the type of radiation, the amount of radiation that reaches the cell also has an effect on how successful the radiotherapy process is and the average life of the cell that it is attacking. The term radiosensitivity [16] describes how likely the cell is to be damaged by radiation. Radiation kills the cells that are dividing, but often also affect the cells in tissues that are unaffected by Myeloma cancer. The damage to the normal cells can cause unwanted sideeffects, including the tissue not functioning properly as some of the cells that make up the tissue are dying and not reproducing. Therefore with radiotherapy there needs to be a balance between killing the cancer cells and damaging body tissue. [16] Using radiotherapy to cure Myeloma cancer is a quicker process than using radiotherapy to cure other cancers. This is because cells in the bone marrow reproduce at a fast rate in order to replace the cells in the blood quickly, which is needed so the person does not die from blood loss for example when they donate blood or have a serious injury.

This diagram illustrates how radiotherapy stops the cells dividing.

12

Tomas Mann McLeod

Sources
These are the main sources that have been used: 1. http://www.macmillan.org.uk/Cancerinformation/Cancertreatment/Treatmenttypes/Bi ologicaltherapies/Angiogenesisinhibitors/Thalidomide.aspx 2. Antitumor Activity of Thalidomide in Refractory Multiple Myeloma Seema Singhal, M.D., Jayesh Mehta, M.D., Raman Desikan, M.D., Dan Ayers, M.S., Paula Roberson, Ph.D., Paul Eddlemon, B.S., Nikhil Munshi, M.D., Elias Anaissie, M.D., Carla Wilson, M.D., Ph.D., Madhav Dhodapkar, M.D., Jerome Zeldis, M.D., David Siegel, M.D., Ph.D., John Crowley, Ph.D., and Bart Barlogie, M.D., PhD A non-web source article. 3. http://www.cancerresearchuk.org/cancer-help/type/myeloma/

Reliability of sources
http://www.macmillan.org.uk/Cancerinformation/Cancer types/Myeloma/Myeloma.aspx Macmillan is a highly regarded cancer charity, as well as an information website on all types of cancer. The information it provides its audiences with has to be reliable as many cancer sufferers will visit this website in order to find out information on the disease they have, such as treatment and the cancers causes. As well as giving cancer patients support, it offers an insight on cancer to the public. Ive cross checked the data gained from Macmillan using Wikipedia and Cancer Research to ensure reliability.

This image shows the Myeloma page on Macmillan.

http://www.cancerresearchuk.org/cancer-help/type/myeloma/ Cancer Research is the most highly regarded cancer research charity. In addition to this it has an internet site (this source) that provides information the same way as Macmillan but in a more scientific way, it gives the causes, treatments and details on living with Myeloma
13

Tomas Mann McLeod

cancer. For basic understanding, and deciding to use Myeloma treatments as the subject of this issue report, I used the Macmillan web page, upon further research into Myeloma cancer, I used Cancer Researchs web page. In order to ensure the facts used are correct from this site I cross referenced them with other sources, including Wikipedia and Macmillan. This website was useful as it gave me a lot of the basic information on Myeloma cancer and Thalidomide; this was useful as it provided me with a foundation for information however it was not helpful when trying to find detailed information. For example Cancer Research had the different types of Myeloma but did not tell me what the different types were.

These two are both likely to be truthful and thorough with their content as they are a nonprofitable organisation that has no profit motive and therefore there is no need for the information to be biased as theyre not attempting to sell their services. In addition to ensure their reliability in the information they have provided I have cross checked them against http://bloodjournal.hematologylibrary.org/content/111/8/3968.full and http://en.wikipedia.org/wiki/Multiple_myeloma.

14

Tomas Mann McLeod

Bibliography:
http://www.macmillan.org.uk/Cancerinformation/Cancertypes/Myeloma/Aboutmyeloma/Wh atismyeloma.aspx (Macmillan Myeloma information page all paragraphs) - last accessed on 14th January 2014 [1]

http://www.myeloma.org.uk/information/facts-and-figures/ (Myeloma facts page facts 110) last accessed on 14th January 2014 [2]

http://www.myeloma.org.au/Portals/0/images/graphics/figure1.jpg (Image on Myeloma bone marrow) last accessed on 12th January 2014 [3]

http://www.cancerresearchuk.org/cancer-help/type/myeloma/about/types-of-myeloma (Different types of Myeloma cancersall paragraphs) last accessed on 10th January 2014 [4]

http://www.macmillan.org.uk/Cancerinformation/Cancertreatment/Treatmenttypes/Biological therapies/Angiogenesisinhibitors/Thalidomide.aspx (Thalidomide information all paragraphs) last accessed on 17th January 2014 [5]

http://images.medscape.com/pi/features/drugdirectory/octupdate/CEL02200.jpg (Image of thalidomide pill) last accessed on 15th January 2014 [6]

15

Tomas Mann McLeod

http://www.cancerresearchuk.org/cancer-help/aboutcancer/treatment/chemotherapy/about/how-chemotherapy-works (Chemotherapy information first 3 subheadings) last accessed on 15th January 2014 [7]

http://www.macmillan.org.uk/Cancerinformation/Cancertreatment/Treatmenttypes/Supportiv etherapies/Steroids.aspx (Steroid information first 3 subheadings) last accessed on 15th January 2014 [8]

http://static.guim.co.uk/sys-images/Guardian/Pix/pixies/2009/4/20/1240266113308/Cancerchemotherapy-001.jpg (Chemotherapy image) last accessed on 15th January 2014 [9]

http://seer.cancer.gov/statfacts/html/mulmy.html (Myeloma fact sheet picture) last accessed on 16th January 2014 [10]

http://www.sciencemuseum.org.uk/broughttolife/themes/controversies/thalidomide.aspx (Thalidomide history first 2 paragraphs) last accessed on 16th January 2014 [11]

http://www.bupa.co.uk/intermediaries/int-news/int-bupa-updates/bupa-updates-archive/costof-cancer-report (Cancer cost table) last accessed on 15th January 2014 [12]

http://www.pharmatimes.com/article/11-0728/NICE_OKs_Celgene_s_Thalidomide_for_multiple_myeloma.aspx (Cancer cost) last accessed on 17th January 2014[13] Antitumor Activity of Thalidomide in Refractory Multiple Myeloma (Myeloma being cured by thalidomide) last accessed on 25th January 2014. [14]

http://www.cancerresearchuk.org/cancerinfo/cancerstats/keyfacts/myeloma/myeloma#mortali ty (Myeloma cancer stats) Last accessed on 15th January 2014 [15]

http://www.cancer.org/treatment/treatmentsandsideeffects/treatmenttypes/radiation/radiationt herapyprinciples/radiation-therapy-principles-how-does-radiation-work (how radiotherapy works to cure Myeloma cancer) Last accessed on 15th March 2014 [16]

16

Tomas Mann McLeod

http://answers.yahoo.com/question/index?qid=20071115120515AAcl2TB (Different types of immunoglobulins) Last accessed on 15th March 2014 [17]

17

You might also like