Another treatment delay

Yesterday provided a reminder that I really shouldn't take things for granted with this disease. I was due for my seventh cycle of treatment with Trabectedin but it had to be postponed because my neutrophil (white blood cell) count was too low. The same problem delayed the start of my second, third and fourth cycles of treatment. However, since changing from a three to four week interval between cycles, I had assumed that my blood count wouldn't be an issue going forward. The oncology ward doesn't have a bed available on Monday so my treatment is now scheduled for Tuesday next week. 

 

In most people the drug causes their neutrophil level to drop just a few days after they receive the Trabectedin, however in my case the delay between the drug entering my system and my neutrophil count dropping is much longer. I've spoken to the oncologist about this and there are three ways to manage it. The first is to increase the delay between treatments, the second is to reduce the dose and the third is to use drugs to try and boost my immune system. We've tried the first of these so it will be interesting to see if the oncologist wants to look at options two or three. The problem with options one and two is that they reduce the total amount of Trabectedin received, something that is likely to reduce how effective the drug is.

 

Assuming that my next scan shows that Trabectedin is still working then my main concern is that I might eventually be forced to stop taking it because my blood count issues mean I can't get a high enough dose to sustain an impact on the cancer. On the bright side I've been quite lucky not to have picked up any infections so far despite spending considerable periods of time with an impaired immune system.

 

Something a little different from me on the photographic front for this post. Recently Katie and I went to a US civil war re-enactment that was held at the American Museum in Bath, I don't usually take pictures of people but I decided to give it a go and here are a couple of the results.

 

 

 

 

Treating LMS: Part II

In my last post I discussed how the classical types of cancer treatment (surgery, radiotherapy and chemotherapy) can be used to treat LMS and explained some of the limitations of these treatments in regard to my own case. In this post I look at some of the more recent forms of cancer treatment and consider how these might apply to LMS.

1. Targeted Therapies. Gastro Intestinal Stromal Tumours (GIST for short) are a form of cancer that has some similarities to LMS. Up until a few years ago patients who had inoperable GIST found themselves with an extremely poor prognosis. In the late 1990's a new drug was discovered, Imatinib (sold as Glivec in Europe). This drug was one of the first examples of a "targeted therapy". Rather than indiscriminately killing fast dividing cells (the mechanism through which chemotherapy works), Imatinib targets only cells that express a particular genetic mutation. That mutation is absent from normal cells but present in many GIST tumour cells. Imatinib represented a massive improvement in the treatment of patients with GIST and has resulted in significantly extended lifespans. The range of cancer types for which targeted therapies exist is slowly expanding and now includes some forms of common cancers like breast cancer and lung cancer.
   
   There is no targeted therapy available for LMS today. However, earlier this year a group of researchers published a paper in which they identified two drugs as candidate targeted therapies for some LMS tumours (Cantharidin and MG-132). There is a huge amount of work to be done to investigate these drugs further but this research paper does raise the possibility of a targeted therapy for some LMS tumours becoming available in the next few years.
    
2. Immunotherapy. The immune system is often 'disarmed' by cancer cells so that they are not attacked by it. In some cases, cancer cells may actually evolve mechanisms that trick the immune system into working on behalf of the cancer by helping it to invade tissue. Immunotherapy looks at how the immune system can be triggered to recognise cancer cells as something it should attack.
   
   As with targeted therapies, there is no proven immune system therapy available today for LMS however, in January 2012, a research paper was published in which a protein, CD47, was identified as playing an important role in preventing immune system cells from attacking some types of LMS cancer cells. Furthermore, the researchers found that by using anti-CD47 antibodies it was possible to reactivate the immune system so that it attacked LMS cells in mice producing a significant reduction in tumour size. Further work is now underway to investigate this therapy with the intention of performing a clinical trial in humans in the next year or two.
   
   
3. Anti-Angiogenesis Agents.  Cancer cells need a rich blood supply in order to grow. To get this blood supply the cancer cells issue chemical signals that stimulate the growth of blood vessels ('angiogenesis' is the name given to the growth of new blood vessels). Finding a way to block the growth of these blood vessels offers a way to 'starve' tumours of the nutrients they need and is, therefore, a route through which cancer can be treated.
   
   Earlier this year the USA's Food & Drug Administration approved the use of the anti-angiogenic drug Pazopanib in the treatment of a number of types of sarcoma including LMS. Approval was granted based on the outcome of a trial which showed that Pazopanib could block tumour growth for some patients although in general this effect was only sustained for a relatively small number of months. Whilst it has not been approved in the UK National Health Service yet, Pazopanib is already being used to treat some UK based LMS patients and so is a potential option for me to consider in the future. 

The research outlined above offers real potential for advances in LMS treatment. It is important to realise that developing a new treatment is a long road with many hurdles that must be overcome and the vast majority of therapies fail on route. Despite that, these new forms of treatment do offer potential for a breakthrough and therefore provide some hope to people in my situation. I will post more about these treatment types as and when there is news on their development.

 

I'll end this post with a splash of colour from a recent trip to the zoo, a blue and gold macaw.

 

 

 

 

 

Treating LMS: Part I

Over the last eighteen months or so I’ve spent a considerable amount of time researching my illness and its treatment. I thought it might be of interest to share a summary of my understanding from this research focusing on where new developments in treatment might be of help to me. I’ve decided to split this into two blog entries, the first looking at well established cancer treatments and the second at some of the newer therapies.

Classically there have been three main techniques for treating cancer, including LMS:

1. Surgery. Surgical removal of cancerous tissue can be performed in order to cure the disease (by removing all trace of it from the body) or it can be palliative (removal of tumours that are causing the patient to suffer symptoms with the aim of relieving these). For LMS surgery is considered the ‘gold standard’ treatment and the best hope of a cure. For curative surgery to be viable it must be possible for the surgeon to remove all of the LMS tumours and a sufficient margin of healthy tissue surrounding them to ensure that all of the cancer cells have been excised.
   
   In my case curative surgery has never been judged a viable option as the cancer is in too many parts of my body, too close to vital tissues and, in my liver, takes the form of many ill defined and diffuse tumours. What’s more the fact that my cancer has already demonstrated the capability to spread to distant parts of my body means that surgery would be very, very unlikely to remove all the cancerous cells even if all the tumours visible on CT scans today could be removed.
   
   Whilst surgical techniques for removing tumours are improving all the time, for instance with the use of robots to assist surgeons in operating with greatly improved accuracy, nothing in my research makes me hopeful that curative surgery could become something of use to me based on these developments alone.
   
   Whilst it is extremely unlikely, should I have a near complete response to my current or a future chemotherapy treatment resulting in the vast majority of my cancer vanishing and leaving just a handful of tumours I would discuss curative surgery again with my oncologist. I should make it clear though that removal of all the tumours in my body is unlikely to remove all of the cancer cells so there would be a high probability of a reoccurrence. 
   
   Palliative surgery could be of use to me in the future, particularly in regard to the abdominal tumours I have which, if they should grow, could cause blockages in my digestive tract that could be life threatening if not removed.
   
   
2. Radiotherapy: Solid tumours, such as those found in LMS, can be destroyed by exposing them to radiation. In the past Katie and I have discussed the use of radiation with my oncologist particularly in regard to its suitability to target my liver tumours. My oncologist consulted a colleague from the Royal Marsden’s sarcoma centre and they both agreed that the treatment would not be suitable in my case.
   
   As with surgery, radiotherapy techniques are improving all the time especially with the use of computer controlled machines to administer the treatment in safer and more accurate ways. However the number and diffuse nature of my liver tumours continues to make them unsuitable candidates for this kind of treatment.
   
   There is another, more fundamental factor that indicates against the use of radiotherapy in my case. There is evidence that cancer cells in which the TP53 gene is damaged may not respond well to radiotherapy as it is thought that radiotherapy kills cancer cells through a cellular pathway that requires functioning versions of this gene. Furthermore, for people with one mutated copy of TP53 in their normal, non cancerous cells there is an increased risk that exposure to radiation could cause additional cancers. 
   
   
3. Chemotherapy: Chemotherapy is a systemic treatment that exposes all cells in the body to cytotoxic (cell killing) chemicals. These chemicals are generally designed to target cells that are dividing, a behaviour that is particular prevalent in cancer cells. All of the treatment I’ve received to date has been chemotherapy; I've just completed my 15th cycle of treatment today and have received 27 infusions of chemotherapy drugs in total.
   
   LMS is not the most responsive cancer to chemotherapy and most of the recognised drugs used to treat the disease have relatively low rates of response. Research also shows that the response rate to chemotherapy in LMS decreases with each different agent used. Cancers also have an annoying habit of evolving immunity to cytotoxic drugs to which they are exposed.
   
   There are a couple of significant areas of advance in chemotherapy treatments; the first is the introduction of new agents approved for use in LMS. Trabectedin, the drug that I am currently using, was only approved for use in the last few years. The second area, not to be underestimated, is that progress is gradually being made in finding ways to better control the side effects produced by these very toxic chemicals. The importance of this second point cannot be overstated given that many patients have to discontinue their use of chemotherapy treatment because of the severity of the side effects.
   
   There are a number of clinical trials running today that are looking at the efficacy of several new chemotherapy drugs or at the efficacy of combinations of drugs in sarcoma. Trials take several years to run and then the process for drug approval by NICE can also take some considerable time so even if some of these trials identify effective drugs it will be some time before they are available to be used outside of the trial environment.  The research that I’ve done doesn’t suggest that any of the drugs currently in trial are likely to provide significantly better response than the existing approved agents. 

In conclusion these classical approaches to cancer treatment, once curative surgery is removed as an option, are all essentially palliative in nature in LMS. Based on my research it seems highly improbably that any of these treatments are likely to offer, in the near future, a means to a cure in my case. That’s not to say there is no hope here at all but we’re looking at very, very long odds indeed; however the improbable sometimes happens, I guess I’m looking for a good ‘black swan’ event!

In the meantime systemic chemotherapy has been doing a useful job for me in terms of palliative treatment and I’m hoping that the Trabectedin continues to perform for many more cycles. Radiotherapy and surgery may be useful in the future depending upon the course of my disease and my requirements for symptom relief. Then of course there are the less well established treatment types which are the subject of my next post.

 

 

Scotland

This is my first blog post since the 2nd of September as I haven't had anything to report regarding my illness in recent weeks. Being on a four week treatment cycle certainly has benefits, I get substantially longer periods of time during which I have few or no side effects from the chemotherapy and this makes being on treatment much more tolerable. I'm due to have my next chemotherapy treatment this coming Thursday and Friday with my next scan scheduled for the week of 5th November.  

 

Katie and I have been on holiday to Scotland for a week. The main aim of the trip was to see some of the local wildlife. We were lucky enough to see most of what we wanted to including dolphins, badgers, three species of deer, a number of species of birds (including a fishing osprey), some very cute red squirrels and a pine marten. Here are a couple of those red squirrels:

 

 

 

 

Aside from the wildlife the scenery is also quite something, especially when the sun shines.

 

 

We're hoping to return to Scotland in the spring or early summer next year. I've discovered an estate near Aviemore that has a photographic hide overlooking a pool in which osprey fish and I'm very keen to have a go at photographing the action.   

Latest treament update

I received my fifth Trabectedin treatment last week. It certainly feels better going into hospital on the back of my  positive scan result, it makes a lot of difference to know that the cancer has been responding.

 

In discussion with my oncologist we've decided to switch from a three week to a four week treatment cycle as my blood counts are consistently too low to enable me to receive the treatment three weekly. On the downside this means that my tumours are being exposed to the Trabectedin less often than is recommended but there are a couple of significant positives too, the first is that being on a four week schedule gives me a whole additional week to get over each cycle, something that could be very useful if I am on the drug long term and secondly the four week schedule should allow Katie and I to make plans much more reliably than we've been able to whilst I've been on the ever slipping three week schedule. The positive results shown by my scan were achieved when I was having the drug once every 25 or 26 days so extending to a 28 day cycle will hopefully not reduce the effectiveness of the treatment.

 

The patient in the next bed to me in the ward on Friday was a sixty four year old man with terminal lung cancer. He's a smoker and was in no doubt that that is what has caused his illness. Despite this he's still smoking - though he did say he had cut down a bit. As he said the damage has been done and there is not much point in him trying to give up now. I don't want to preach but if you are a smoker you really should stop, it's just about the most important step you can take to reduce your risk of cancer.

 

The rugby season has started and Katie and I are hoping to take in a few matches over the coming months. We went along to a pre-season game between Bath and London Welsh, I took my camera - here's the Bath wing Tom Biggs having a bad hair moment as he offloads the ball in a tackle.

 

 

 

 

 

 

  

 

 

Here's to Ecteinascidia Turbinata

Today has been a very good day, Katie and I got the result of my most recent scan which showed that the current chemotherapy has had a significant effect on my tumours. It's very difficult to give a quantitative estimate, but from comparing my two most recent scans I would guess that the largest tumour in my liver now has a radius that is between two thirds and a half of what it was in April. The radiologist's report states that all the tumours are shrinking. The statistics suggest that Trabectedin produces significant shrinkage of tumours in fewer than 20% of LMS patients so it was far from a foregone conclusion that the drug would work.

As I noted in a previous blog entry the active compound in Trabectedin was first identified in a Sea Squirt -   Ecteinascidia Turbinata, hence the title of this post. To celebrate our good news Katie and I went to the pub on the way home from the oncology clinic. I had half a beer and Katie and I toasted our new favourite marine filter feeder. I'm not supposed to drink alcohol whilst on Trabectedin but there are times when a beer is essential. It was the first alcoholic drink I've had since mid-April and it tasted very good!

The plan now is to continue with further cycles of Trabectedin for the next three months; I will then have another scan to see if it is still working. While the tumours continue to shrink or remain stable in size and I continue to be able to tolerate the side effects I will stay on this drug. My oncologist told us that he has a patient who has been on Trabectedin for over a year and there are examples of people who have had the drug for considerably longer, so I'm hoping for a good run here.

On Friday last week Katie and I got up at 5am and drove over to Dundry Down, a hill just to the south of Bristol. We went there to watch the mass ascent of balloons at the Bristol Balloon Festival. The balloons are launched from Ashton Court Estate and the launch site is visible from Dundry Down. It was pretty misty so it was not much of a day for photography, however I did manage to get a few shots that I could salvage on the computer. The distance from the hill to the launch site is around three miles as the crow flies, so taking that into account along with the mist this one has come out reasonably well: 

“Fighting cancer” – a personal view

Current and recovered cancer patients often refer to their experience with their disease as a fight, a battle or a war. Nothing here is intended as a criticism of those who view their experience in those terms, indeed it is clear to me that for many cancer patients this is a useful paradigm, however I can say that it’s not one that appeals to me.

A number of members of the LMS e-mail forum that I subscribe to refer to LMS as a ‘dragon’ and to their own experience as ‘attempting to slay the dragon’. This is not a metaphor that works for me, if I saw a dragon I would be thrilled, delighted, awed and very keen to photograph it (ok, I might be petrified and surprised too)! The thought of slaying virtual dragons is not something that brings me positive feelings.

When I was first diagnosed with cancer I sent an e-mail to some of my colleagues to update them on my situation. In that e-mail I made a reference to my intention to fight the disease. At that time I hadn’t had chance to really understand my feelings about being ill and my thoughts were shaped in part by a thought that others would expect me to adopt an aggressive attitude towards my condition. One of my colleagues replied to my message by writing that looking at engaging in a battle with cancer might not be the best way to proceed. He’d read something that suggested that entering fight mode might promote emotions that are not conducive to healing. He suggested it might be better to consider my chemotherapy treatment as a flock of sheep nibbling on the green grass of the tumours! Whilst I found this rather bizarre bucolic image to be amusing it did tally with my feelings towards my cancer.

Since becoming ill in February 2011 I’ve been very lucky in that I've managed to retain a positive outlook most of the time. Sure there have been some pretty low points, particularly around those times when we’ve received negative news on the progress of the disease or its treatment, however in general these moments have been short lived and I’ve soon returned to an even emotional keel. Frustration has perhaps been the most common negative emotion I’ve felt, this in regard to the disruption the illness and its treatment have caused to my life and to Katie and my ability to plan and to travel, but again this is not a feeling that dominates my waking hours.

In terms of my disease I have felt very few negative emotions towards it. I think this is because I see my cancer as almost certainly being the result of the TP53 genetic mutation that I posses. There is no external pathogen that is causing my disease, the tumour cells are my own cells albeit with mutated DNA and those mutations have themselves taken hold because of an inherent part of my genetic makeup. Anyway I find myself without any anger or rage to direct at my cancer.

When I think about addressing my illness it is usually pleasant and positive emotions that I feel more comfortable with. In the main these thoughts and feelings are about nurturing my body, healing, calmness, the beauty of the natural world and taking pleasure in everyday life. I also feel very motivated to control the amount of time I give to my illness, I have a lot of things to do that are more fun than researching my medical condition or attending medical appointments. Fighting a battle is a full time job and I do not feel that would be time well spent for me.

I want to make it clear that I don’t see my approach as giving up or risking a worse outcome, I just see it as a way of managing my condition that is true to my feelings and true to my goals of balancing both my quality and quantity of life. I like to be guided in my approach to my cancer by scientific evidence and to date I’ve seen nothing to suggest that the mental attitude of cancer patients influences the outcome or duration of their illness. Mental attitude is, of course, very important in determining the quality of a cancer patient’s life, but in my view quality of life may be better influenced through positive emotions than through the emotions associated with battle.

As I wrote at the beginning of this blog entry, I understand that many people find tackling their disease as if it were an opponent in a battle to be of great utility, however this approach is not right for me. If having cancer is a war then I guess that means that I am a conscientious objector and I'm very comfortable with that.