clinical trials

Interlace Clinical Trials

by Tara Millar
So here’s the deal. Answers to most of your questions that you will have to any trials is to remind you that they are trials. There are no definite answers. No promises made, there is no concrete evidence to provide because this is a trial. These aren’t new drugs but a new way of treating my type of cancer, Stage 2b Cervical.
Interlace is in its Phase 3 where humans have already undergone tests in previous phases and thus far they feel that progression to phase 3 has been deserved by findings so far. But nothing can be published officially until a larger group of patients have been through the trials.

1999 was the last time a clinical trail for cervical cancer was carried out. It reported that combined radiotherapy along side chemotherapy would improve survival rates. Now this is standard treatment. This was 16 years ago and no other clinical trail has been run since thus no further improvements for how to defeat Cervical Cancer have been researched nor found. Until now! 2015 sees UCL (University College of London) running the Interlace trails. This trail administers 6 doses of induction chemotherapy (prior to the standard treatments) of Taxol and Carboplatin.

This Chemotherapy is designed to reduce the size of the tumour, prevent metastatic (free radicals carrying cancer to other parts of the body) and to prevent reoccurring cancer.
You are given a large document to read at home and in your next visit you will re-read everything again, with space for questions from the medical and clinical trails team. Then I also did extra questioning via email over that weekend which felt good as they were written answers – enquiring of about the phase two trials and what evidence was found etc. Everyone who works in oncology, clinical trails and the surrounding faculties is very careful with their wording. They are careful not to scare you and to use the correct words that can not be misconstrued. There is absolutely no force in choosing to do or not to do the trials. They are no empty promises, it is not their purpose to recruit you and I felt under no obligation to commit. It really is an open decision which for an NHS patient, whom, being accustomed to trusting the advice of doctors this can feel like foreign ground. Your treatment now comes into your own hands and you need to make a decision. So let it be an informed one I say.
Purpose of Study
Make standard treatment more effective by first shrinking the tumour
Aim to reduce risk of reoccurring cancer and stop metastatic cancer (cancer in other parts of my body)
Pro
It will make the 6 week treatment more effective at combating cancer by reducing the tumour volume
Con
It will take an extra 6 weeks for overall treatments – meaning side effects for longer and halt of normal activities
Pro
It tackles cancer that may or may not be moving around the body (micrometastatic disease)
Con
Cisplatin may also do this
Pro
You will be hitting cancer with three types of chemo as resistance to Cisplatin is possible
Con
You might not need it
Pro
You feel like you are doing everything you can to defeat this disease
Con
It might still come back
Pro
It isn’t every day that someone gets to try out a new method of combating cancer, one day this may be the normal way of tackling the disease and you got to benefit from it
Con
It might not be and I will lose my hair.
The main issue I had to get over was the losing of the hair. I have long curly hair which has taken so long to grow and keep healthy. I would look totally different, I wouldn’t be able to play with my locks and what if I needed to change how I dressed in order to match my hair style? My hair was my identity, it was my ego. I look up photographs of GI Jane and Alien. They do look kickass, but in Northern Ireland it is cold! I struggled with this for some time. Until now I don’t ‘look like a patient’ and so choosing this trial I would become a face of cancer in society. People would know. My hair would be gone.
The more and more that played on my mind, the more I began to dislike my hair. I really felt that it was getting in the way of making an informed decision about my health. Yes I knew it would grow back so why did it bother me so much? It would be gone, but then it would return. People would know I am going through cancer treatment – but they should know! People should get themselves checked because cancer is real! I didn’t want to mess with this. Cancer isn’t something to mess with, my hair can come and go but cancer, no, I need to deal with this in the best more effective way possible. I need to kick this thing’s ass for good. Throw everything I can at it. If I am currently at a survival rate of 75% chance of living for the next 5 years and I can increase that even by like, 5%, I’m taking that extra 5%.
I took my hair out of the equation. “If I didn’t lose my hair, would I enter the trial?” I asked myself and a big fat YES came pounding out and I knew that was what I must do. I needed to face losing my hair head on and make a decision that could ultimately aid to me living for longer. And what if the trail wasn’t of any use? It wouldn’t harm my standard treatment by delaying it – the trial wouldn’t exist if that was the case putting the patient/cancer diva in jeopardy – but at least I knew I was doing everything in my power to defeat the cancer. I imagined the regret I would have if I turned down the Interlace trial and the cancer returned and how awful on top of that would it be if the trials are a success and now that was the normal standard treatment. I couldn’t bare that thought. So I signed the consent forms, and got ready for Chemo Day 01.

Chemotherapy

by Tara Millar

What is it?

A drug that works through your blood to ‘treat’ cancer. Where surgery and radiation are local treatments targeting only where the tumour is, chemotherapy attacks cells, all cells (cancerous and normal), throughout the body. This helps if it has spread (Metastases).
All cells divide and grow. Normal cells know when to stop dividing and growing when they come into contact with similar cells. Cancer cells do not have this turn off switch thus keep multiplying and building up as a tumour.
Chemo or ‘Chemical Treatment’ or ‘Treatment with Cell Killing’ halts the division process. This causes the tumour to shrink or become tumorcidal (cell suicide). There are cell-cycle specific chemo drugs (for when cells are dividing) and cell-cycle non-specific (for attacking the cells when they rest) But mainly the cell-cycle specific drugs are the chemo drugs we use most often. These affect cells that divide and grow quite often – other cells of this nature include stomach and bowel cells for example, as they regrow in order reline the stomach when digesting. Hair and nail cells are also constantly growing, skin cells too as they replace new skin all the time and bone marrow, which produces your blood cells. So these are also affected by chemo drugs. And, as you can imagine, I may notice changes to these more frequent areas with side effects. So far chemo is unable to decipher between cancer and normal cells. The good thing is that the normal cells grow back only.
History of Chemo drugs
So, Chemotherapy was discovered during the use of chemical warfare in World War 2, in the use of Mustard Gas. One part of the gas, Nitrogen Mustard, in particular. When a group of soldiers were exposed to the mustard gas, upon inspection of doctors, they found that their white blood cell counts were low and that it had affected their bone marrow and lymph nodes. From this discovery doctors explored using this agent and thought it may help fight diseases like lymphoma and cancers. They tested it on animals and found that it worked. It wasn’t until 1946 (after the war and secrecy of these gas programs, that findings were published). Then in 1955, interest was big to discover more chemicals against cancer which then lead to a national screening program.
However, at this time Nitrogen Mustard effects did not last long. They began using various drugs to combat Childhood Leukaemia and Hodgkin’s disease. There was a 50% remission rate, which lasted longer. Around 1970 people began to now believe cancer was curable which was a force to bring to bear, as scientists believed there was a possibility of finding a cure so then were granted time and money and approval to focus their work, and it research progressed.
What Chemo drugs am I receiving?
There are hundreds of different chemo drugs. My standard treatment will use Cisplatin – the most common. The clinical trial, Interlace, will provide me with Carboplatin & Paclitaxel (Carbo/Taxol) or PC. All three of these chemo drugs are listed on the World Health Organisation List of Essential Medicines.
Carbo/Taxol is normally given every three weeks over 5/6 months when sometimes administered for Breast Cancer. In my instance in this trial, I will be having this first, but every week, and for 6 weeks. Thus, the dosage is one third of its normal amount given and this amount is also based on my body mass to see how much my body can handle. They give you the max amount and can be adjusted, incase I can’t cope for example. Little bit of experimentation along the way sure, why not!
Paclitaxel, aka Taxol, is made from pine needles from the Yew Tree. Well, it used to be. The demand for the drug at its discovery was higher than the ability to harvest the trees so Robert A Holton, a professor of Florida University, began synthesising the drug. It was discovered in 1962 during the time when the National Cancer Institute had put on a screening program to collect samples of a 1000 plant species per year.
A man, by the name of Arthur S Barclay, had collected bark during this screening program, from the Pacific Yew Tree and when processed by subcontractors, they found it was cytotoxic (Cancer cell killing). It was developed commercially by Bristol-Myers Squibb (BMS) with some controversies along the way. A lot of controversies actually. Financial ones at that.
In 1978, mice, with leukaemia, were the first to benefit from its effects. In 1979 Susan B. Howitz published that Taxol had the ability to stabilise microtubules (these microtubules undergo continual assembly and disassembly of cells. They determine the shape of cells in a variety of movements, the intracellular transport of organelles, and the separation of chromosomes during mitosis – yes you are thinking, ‘basically’) Paciltaxel works by stopping the doubling of cancer cells. In 1982, trials for humans began.
After Phase 2 of these trials, ecological concerns were voiced, even though they had been having remarkable responses in ovarian cancer patients. About 360,000 trees were needed each year to provide enough bark for the drug to be made. This sparked the need to reach out for help, financial help, in order to further clinical trials and handle the isolation of taxol. This received a lot of fleck as one company bought exclusive marketing rights of the life saving therapy drug. They went on to make over $1billion dollars of profit from Taxol, using Robert A Holton’s synthesising methods. He got rich, Florida State University got rich and so did Bristol-Myers Squibb. The cost of Taxol? – if you had four cycles of treatment with Taxol, it would cost the NHS £4000 ($6000).
Carboplatin & Cisplatin
These are cell-cycle non-specific drugs meaning it attacks during the rest phase of cell division. They are platinum based drugs, discovered in the ’80s. Carboplatin was made after Cisplatin (parent drug) and has fewer side effects.
Cisplatin was discovered by accident. A researcher, named Barnett Rosenberg, wanted to explore the effects of an electric field on the growth of bacteria. When the bacteria stopped dividing once it was placed in an electric field, he found that it was because of the electric field of the platinum electrode rather that the field generated itself. Thus cell division in this way was explored further in rats – alas, successful results gained approval for human use and in 1978 in US, 1979 in UK, Cisplatin was used to treat ovarian and testicular cancer.
When the compound enters a cancer cell it becomes positively charged when water molecules replaces its chloride ions (further research is looking at how to manage the amount of chloride we have in order to boost a maximum effect). This charge attacks the DNA charge, creating cross links in DNA making it hard for the cell to duplicate that DNA section, thus dying.
There is, unfortunately, resistance to Cisplatin that can occur. In situations where this is the case, Paciltaxel (Taxol) is used to boost its effect – reasons are unknown why this works so far but discovering this during my research makes me glad I opted for the Interlace trial! (Cisplatin is administered as the Standard Treatment, Taxol as part of the Trial I was fortunate to take part in). Also various studies and meetings are held across the globe that discuss aspects of the drugs uses; in San Diego they are discussing the possibility of predicting the resistance of cancer cells to Cisplatin by measuring DNA damage. In Scotland and Australia, they are discussing the possibility of using external magnets to draw the platinum-based Cisplatin to the targeted tumour. In MIT, a professor is restructuring the platinum compound and his research indicates a 4-40 times higher potency to cisplatin so far. Isn’t this so interesting! I loved knowing so many really intelligent people were working all round the world, trying to make it all better.
I’m basically throwing three DNA suicide bombs on the tumour, not just one. Sometimes DNA repair pathways become resistant to a particular chemo drug and due to ongoing research, we are still unable to accurately predict how one person will be affected by any particular chemotherapy, if the tumour becomes resistant and if it grows back. There are many unknown elements that may happen and yet there is still an outstanding amount of success to the treatment of cancer.
Now for the ‘fun’ bit of this post…..random side effects.
Along with the predicted side effects (feeling crappy, hair loss, fatigue, etc) I found some side effects that were offered an amusing surprise. I’ve not decided if I am alarmed or just plain old, amused:
Loss of hearing
Loss of taste
Electric shock when bending your neck
Loss of colour vision
Hiccups. Yes, hiccups.
Increased risk of developing cancer. Yes, you can re-read that again. Crazy.
Yellow eyes and skin – what is the solution for this. Must ask Vogue.
Burning hands and feet – So, jandles in winter?
No urine output – if over 12 hours this is a serious emergency I’d suspect!!

Got Cancer? Here’s some booklets to read

by Tara Millar

So I was diagnosed, then scanned to see how far the cancer had extended and now the planning for treatment begins and there is a wait of about two weeks.

You are given about 6 different booklets: Understanding Cervical Cancer, The Cancer Guide, Understanding Radiotherapy, Radiotherapy – Your Questions Answered, Understanding Chemotherapy. And then you can get more. I chose: Travel & Cancer and Cancer & Exercise. These are made by Macmillan Cancer Support and HSC (Hospital & Social Care trust).

Granted, most people I have spoken to didn’t want to know anything about their diagnosis nor treatment and are happy to follow the doctors orders – so look away now if this is you, however if, like me, you have an Alice in Wonderland approach in life, that only find things like this ‘curiouser and curiouser’ then we must try to understand everything in order to keep our sanity and give us a sense of control.

So here goes…..this isn’t exhaustive but all of these things relate to me:

Understanding Cervical Cancer

  • Cancer is the disease of cells
  • The disease causes cells to develop into a lump/tumour
  • A malignant (cancerous) tumour may spread to nearby tissue
  • It may also travel through your body via your bloodstream or lymphatic system
  • Lymphatic system (part of immune system) includes lymph nodes
  • These lymph nodes are connected via ducts (tubes)
  • Lymph nodes are all over the body – pelvis, abdomen, armpit, neck etc
  • Cancer of the cervix is usually the result of HPV from sexual activities
  • Condom or no condom does not determine being infected
  • HPV may lay dormant and pass through your body or may turn cancerous
  • Girls are now vaccinated against HPV (hooray!)
  • There are various stages of cancer 1A-4B
  • I am 2b meaning it spread to nearby tissues and lymph nodes in pelvis area
  • They call this Locally Advanced Cervical Cancer
  • Treatment for this is Chemoradiation (chemotherapy and radiation combined)
  • My para-aortic lymph node/glands might also be infected and will be surgically removed to check under microscope
  • The team deciding your treatment consists of; a Gynae, a Clinical & Medical Oncologist (someone who deals with tumours medically) and a Specialist Nurse
  • There are lots of side affects to Chemoradiation, it may even give you cancer
  • Radiotherapy uses high energy x-rays to kill cancer cells
  • This can be external, internal or both
  • External radiation uses small tattoos (permanent) to align an area of concentration
  • Radiation is given Mon-Fri, with rest at weekends, and lasts 10-15 mins each time
  • Radiation does not make you radioactive and you will not be harmful to pregnant women or young children
  • Internal radiation is given afterwards and you will have this inserted into you
  • The applicators are inserted under sedation or general anaesthesia
  • It will be uncomfortable
  • Chemotherapy uses anti-cancer drugs to destroy (cancer) cells
  • There are various types of chemo drugs with different functions
  • The most common is called Cisplatin
  • This is platinum based drug and will be used in my standard treatment
  • It is injected into you and flushed out of you within one day per week (sessions could last 8 hours)
  • During treatment your bloods are taken each week to see how your body is coping
  • After treatment you are checked every 3 months for 6 months (if in a trial)
  • Then every 6 months for the next year and a half (as normal)
Alongside all of this treatment, the six weeks of chemoradiation, I was approached about the clinical trials, Interlace.
  
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