Chemo's common companion says hello

Yesterday I finally experienced one of the commonest side effects of chemotherapy. I had my third infusion of dacarbazine which went without problems for the first forty minutes or so, then I began to feel nauseous. By the time the infusion was completed I was feeling very green indeed. It was hot in the chemotherapy day unit and I thought I'd feel better once I got outside into the fresh air, unfortunately I only made it to the oncology centre car park before I began to be sick. That lasted for about an hour, it was an interesting experience being driven back to Bath by Katie whilst repeatedly throwing up - not one I can recommend! Luckily the hospital had given us a number of cardboard bowls so at least it wasn't messy (see, there is always a bright side if you look hard enough!). I went to bed when I got home and felt a little easier after I'd had some sleep. I'm still feeling nauseous today but not to the same extent as yesterday. It just goes to show that you can't make any assumptions about how each treatment is going to go, every one can offer a surprise.

 

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I spend a considerable amount of time researching my illness and possible treatments for it. As part of this I often read scientific papers that present the results of clinical trials and other research. A few months ago I read a report on a piece of research that had been done by a UK based team. This looked at the quality of life of people with advanced soft tissue sarcoma (ASTS). I was interested in this paper for two reasons, first because LMS is a type of STS and secondly because quality of life is one of the factors often considered by regulators when deciding whether a new treatment for a condition is cost effective. Simply put a costly drug that fails to provide a decent quality of life for patients may not be worth funding even if it extends the lives of those patients.

 

The report that I refer to above is entitled "Utility Values for Advanced Soft Tissue Sarcoma Health States from the General Public in the United Kingdom" and was co-authored by Julian F. Guest, Erikas Sladkevicius,  Nicholas Gough,  Mark Linch  and Robert Grimer. The authors of the paper are all involved in research into and/or treatment of sarcoma. The lead author, Julian Guest, also runs his own consultancy business through which this research was conducted. The full report is freely available at this link.

 

When I read the report I had a number of concerns about the methodology used in the research and the conclusions that the report seemed to support. I'm not one for writing letters to the authors of scientific papers, I've never done that before, however in this case I felt that the research was flawed and could be damaging to the interests of ASTS patients if used by regulatory authorities in their assessment of new treatments.

 

My main concern about the research was that it involved asking members of the general public to estimate their preferences for various health states associated with different responses to chemotherapy treatment for ASTS. My own experience convinces me that members of the public, most of whom will not even have heard of soft tissue sarcoma, are unlikely to be able to anticipate how they would react to being diagnosed with an advanced form of this disease let alone to meaningfully comment on how they would feel about various health states following chemotherapy treatment for the illness.

 

I remember well my own initial reaction to my diagnosis which was to fear that I would be unable to enjoy anything in life with this illness hanging over me. I remember too how quickly I adjusted and found that I could enjoy so many things just as I had before I was ill. There is no reason, other than time and cost, that prevented the research being conducted on patients who actually have ASTS. As the authors have themselves accepted in their replies to my concerns, this would be the preferred option for this type of research. I find it interesting to note that two other quality of life studies that did use ASTS patients rather than members of the public both provided higher quality of life estimates than the UK study.

 

I also have a number of concerns regarding the descriptions of the health states used in the research. Whilst I accept that these seek to describe the experience of the average ASTS patient I found them to be written so as to preclude a reader from understanding that those in each state could have a much more positive experience than suggested by the descriptions. Indeed, some of the health state descriptions preclude a patient from having experiences that I myself have had whilst in those health states.  

 

Having initially shared my concerns with the authors of the paper they provided a reply and suggested that, if I was not satisfied, I should write to the editor of Sarcoma, the journal that published the paper. On receipt of my letter the editor asked the authors for a response which they duly provided. Unfortunately, the editor of Sarcoma has informed me that they are unable to publish either my letter or the response from the authors, however I want to make sure that my concerns are in the public domain and so have decided to share them here. Below I provide links to my letter to the editor of Sarcoma and the response from the authors of the paper.

 

• My letter to the editor of the Sarcoma Journal
• The authors' response to this letter

 

For completeness, I also include my rather more detailed initial letter to the authors of the report and the response I received from Dr Mark Linch, one of the co-authors.

 

• My original letter to the papers authors
• The authors' initial response to my letter

 

I'm very supportive of research into patient quality of life in ASTS and other cancers. Such research is of great importance in helping doctors, patients and regulatory authorities decide when certain treatments are appropriate and cost effective. However, research into this topic must be done to the highest standards if it is to be used to make crucial decisions that will have a tremendous impact on patients and their loved ones. In my view, short cuts are not acceptable.

 

The bad news and the good news

Yesterday I had my regular consultation with my oncologist. The second cycle of dacarbazine chemotherapy has been going well with minimal side effects from the treatment, however in the last month I've noticed an increase in symptoms from the cancer. I've been experiencing abdominal discomfort most days with short periods of intense pain. When I have the pain I also have a strong feeling of nausea. The discomfort is made worse by walking and is limiting my mobility a little. The ten mile walk Katie and I did around four or five weeks ago is not something I could contemplate repeating at present. In addition to these symptoms I'm now sure that the several small tumours that I have on the surface of my skin are growing. I discussed the symptoms and the tumour growth with my oncologist and he agrees that it is likely that the dacarbazine is not working.

 

I have a CT scan of my abdomen and chest scheduled for the 26th March so we have agreed that I will go ahead and have the third cycle of dacarbazine next week and that we'll then review the scan results to determine if we need to switch treatments. We discussed what options there are available as a next step. My oncologist has recently presented my case at a meeting of the British Sarcoma Group, he was hoping to get some ideas from his colleagues who may have seen cases like mine before. Unfortunately there were few suggestions other than one idea that we try a chemotherapy regime normally used in ovarian cancer. This has a good record in tumours with no functioning TP53 gene which we suspect to be the case in my tumours too. This would be a speculative treatment as this chemotherapy regime is not used in Leiomyosarcoma and there is no trial based evidence to suggest it would work. I've identified another chemotherapy agent, eribulin, as an option as it has been shown to work in around 30% of LMS patients in a single, small trial.

 

Yesterday's consultation really brought home to Katie and I how close we are to running out of viable treatment options. There is always going to be another drug I could try but you have to question whether undergoing treatments for which there no good evidence of effectiveness is sensible, especially when those treatments can cause very serious side effects.

 

Following yesterday's rather bleak discussions we had some good news today when I saw my cardiologist. The purpose of the meeting was to discuss whether I can take pazopanib. This is a new treatment for sarcoma but has the results of a fairly large phase III trial supporting its use. Pazopanib was the preferred treatment option for me following the failure of trabectedin back in November but concerns about my blood pressure and heart condition meant that it was judged too risky for me. Well now the cardiologist has agreed that given the lack of other options I can go ahead with pazopanib. I'll need to have my heart function and blood pressure closely monitored and there will be an increased risk but this is something I'm willing to accept. I'm very relieved that this is now an option. The doctor I saw today was a registrar and she needs to discuss this with the consultant so the position could change but we're hopeful it won't.

 

So if the forthcoming scan shows the dacarbazine is not working the intention is that I will switch to pazopanib. It's a relief to have a clear way forward with a drug that has a fair chance of at least stabilising my disease.

 

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Katie and I went to the Wildfowl and Wetland Trust reserve at Slimbridge the other day. For the last few years the WWT have been working to reintroduce the common crane into south west England. They've been hatching imported crane eggs at Slimbridge and then releasing the young birds on the Somerset Levels. The hope has been that once old enough the birds would breed on the Levels and establish a sustainable population. Cranes were once common in England but are now very scarce indeed with the last pair breeding in the south west over four hundred years ago. Some of the released birds are now reaching breeding age, amazingly last year a few of them showed up at Slimbridge and a pair tried to breed, unsuccessfully unfortunately. They are back again this year and were busy building a nest right in front of one of the hides. They are very large birds with a very distinctive look as you can see in the pictures below. As they are part of the reintroduction project they have radio trackers and are conspicuously ringed. Let's hope they successfully rear chicks this year.

 

 

 

 

 

 

 

 

A trip to Northumberland

This morning I had my second dacarbazine chemotherapy treatment. As mentioned in my earlier post, we have increased the dose by 25% compared to the first cycle. The new dose is typical for use in patients with sarcoma, I initially had a lower dose so that we could understand the level of side effects that I would experience. In fact the first cycle of dacarbazine has been the most trouble free chemotherapy cycle I've ever had, I'm expecting that this second cycle will be a little more problematic as a result of the higher dose but I'll just have to see how it goes over the next few weeks.

 

I keep a count of my chemotherapy cycles, this current one is the 30th that I've had since starting treatment for Leiomyosarcoma back in April 2011. Some people with advanced LMS are rather sceptical about the benefits of chemotherapy, especially in light of the very severe side effects that people may suffer. My own experience has been a positive one: not only have the side effects been generally manageable, the treatment itself has, in my view, significantly extended my life. Of course this is just my impression and, from a scientific perspective, is merely an anecdote but it does mean that I'm personally very comfortable with the treatment path that my oncologist has been recommending to me and that I have chosen to follow since my diagnosis. There is a relatively low chance that the dacarbazine will actually do me any good, but even if my next scan shows that it hasn't worked that won't change my view on the value of chemotherapy for those with advanced LMS.

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Katie and I recently made a three night trip to Northumberland. Given the windy and rainy weather that has been with us for weeks we really did wonder if this was a good idea, however we decided to take a chance and go anyway. As luck would have it our two days of bird watching on the Northumberland coast coincided with a real improvement in the weather and we enjoyed a lot of sunshine during our trip.

 

We spent some time sat in a hide over looking the Island of Lindisfarne. The sea was a shade of turquoise more usually associated with the Mediterranean than the north coast of Northumberland in February, the vegetation was golden and the sky blue.  It was very relaxing just being there enjoying the view.

 

We hired a local wildlife guide to take us out on the first day of our visit. We've used him once before back in 2009 and we had another very good day this time around. Whilst Katie and I are reasonably good at identifying birds we would miss quite a lot without the help of a guide. The guide has written a blog entry on our trip for anyone interested in the details.

 

I didn't take any pictures so I've picked this from one of our previous visits to the area. This is a shag, a relative of the more common cormorant. I think this bird is really very stylish with striking green eyes, yellow on the bill and an iridescent green sheen in the plumage.

 

 

 

During our trip we stayed at the Red Lion at Alnmouth, a very nice traditional pub that we've also stayed at on our two previous trips to the area. I recommend it if you're looking to visit. 

  

Side effects, what side effects?

I'm due to have my second cycle of dacarbazine chemotherapy next week so I had my routine pre-treatment appointment with my oncologist on Thursday. Overall I've found the first cycle with this new drug to be the best I've experienced in terms of side effects - basically there haven't been any. This is pretty unusual and I've found myself wondering if the saline mixture I was infused with actually contained any dacarbazine! My oncologist was quick to remind me that I shouldn't assume the next cycle will be so trouble free.

 

We've decided to increase the dose of dacarbazine by 25% next week. I'm expecting some side effects but I'm hoping they will be quite mild given the experience from last cycle.

 

The oncologist gave me a copy of the radiology report from the CT scan that I had back on the 30th January. The purpose of the scan was to provide a baseline on tumour size that we will use to compare with my next scan, due in around five weeks time, which will be used to determine if the chemotherapy is working. I'd been off treatment for around eight weeks before the 30th January scan, during that time we knew that the cancer was growing and this was confirmed by the scan results. The tumours in my lungs, liver and abdomen had all increased in size. The good news is that the radiologist didn't raise any urgent concerns regarding this growth and he also didn't identity any new tumours elsewhere in my body.

 

My health has been generally good over the last three weeks although I have been getting more symptoms from the cancer since I stopped taking steroids a week ago. The most significant of these are constipation and stomach/abdominal pain. The pain is easy to manage as it tends to be transient in nature and responds quickly to paracetamol. The specialist nurse from our local hospice had warned me to expect additional symptoms once I discontinued the steroids, this is because the steroids suppress the inflammation that the tumours cause and without them this increases causing pressure on other organs.

 

My oncologist also asked me to continue to refrain from driving until he has spoken to a lymphoma consultant colleague of his. He said that he thinks it likely that I will not be judged safe to drive.

 

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Not being able to drive is going to be a bit limiting in terms of my wildlife photography. Katie is happy to drive me to places but I like to spend a lot of time taking my shots and sitting around watching isn't much fun for her. One of the great things about photography is that a constraint on what or how you can shoot can sometimes help you to be more creative. Here are a few shots from February that were all taken within a mile walk of our house. Hopefully I'll find lots more subjects in the coming months.

 



 

 

 

 

 

 

Seeing the funny side

It's been over a week since I received my first chemotherapy treatment with dacarbazine and I'm really surprised and pleased with how well I've been feeling. I've had fewer side effects so far in this cycle than with any of the previous treatments. My oncologist gave me a lower dose of dacarbazine than would ordinarily be used as he wanted to see what problems it might cause me, I would guess that next cycle we'll be upping the dose to the normal level. This may result in more side effects but given how well this cycle has gone I'm hopeful that they won't be a major problem.

 

We don't know if the treatment is having a positive impact on the tumours. I have several small sub-cutaneous metastases that are visible on the surface of my skin. I've been watching these closely to see if they show any sign of shrinkage but I've not been able to detect any. It's quite possible that the tumours in my liver, abdomen and lungs will respond differently to those on my skin so this does not mean the drug is not working. I'll have to wait until after the next two cycles in order to get a CT scan to definitively determine if there has been a positive response.

 

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Iain Banks, the Scottish author who died last June of gall bladder cancer, remarked that he and his partner found "ghoulish humour" to be a useful part of their strategy for coping with  a terminal prognosis. In the public statement issued on receiving his diagnosis, Banks wrote:

"I've asked my partner Adele if she will do me the honour of becoming my widow (sorry - but we find ghoulish humour helps)."

 

Katie and I have also come to find this type of humour to be useful. Some people will consider it to be in bad taste, but sometimes there is very little that is as effective at changing a mood or closing out a discussion on a difficult or depressing topic than a really good piece of black humour. I emphasise here that I'm referring to making these kind of jokes about my own condition - not about other peoples, clearly that is something else entirely.

 

Here are a couple of examples that stick in my mind, I hope you see the funny side!

 

In September 2011 Katie and I were at the cinema watching the trailers for forthcoming films. The film being advertised was "The Iron Lady", the biopic of Margaret Thatcher. I've always found Thatcher to be an interesting character which is in total contrast to Katie who really had no time for her at all, our conversation went something like this:

 

Paul: "Let's come and see this film, it looks really interesting".

Katie: "It's not out until February, hopefully you'll be dead by then".

 

(We never did go and see the film!).

 

Then there is the birthday card I bought for Katie last year, it featured the following cartoon which seemed extremely apt given the love of wine both Katie and I share.

 

 

 

 



Back on treatmemt

I'm now back on treatment having just had my first infusion of dacarbazine. The drug is delivered through an hour long intravenous drip. The main side effect is nausea although the full range of typical chemo issues are possible. From previous experience I know that I need to wait a week or so to have a good view on my own reaction but for now I'm feeling fine.

 

I got the results of the brain MRI that I had last week. Compared to the previous scan they indicate a significant improvement. My oncologist's view is that this is very positive and that it is also compatible with the cause of the abnormalities being a Lymphoma. I will continue to take steroids for the next ten days or so and will have another brain scan at some point in the future to see if there has been any further change. In the meantime I've been told that I should continue not to drive until my oncologist has had chance to discuss my case with one of his colleagues, hopefully I'll get more information on what they decide soon.

 

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Having a break from chemotherapy has been very welcome. Katie and I have been able to take several shorts trips away which, despite the recent weather, have all been very enjoyable. Last week we were down in Padstow for a couple of nights with friends. This was one occasion when the unsettled weather actually added something to the experience. The sea provided an entertaining display for us with the surf crashing in and breaking in spouts over the rocks. This made a great subject for a photograph or two (click the images to view at larger size).

 

 

 

 

 

 

 

Nelson's coat

My new chemotherapy treatment is starting on the 6th February. This is a little later than I would have liked but it is good to have a date in the diary at last. This will use  dacarbazine.  

 

My oncologist has also confirmed that he is happy to prescribe metformin for me alongside the chemotherapy. I will take an escalating dose of the drug during the first two weeks of treatment before reaching a stable dose (1500mg per day). I'm very pleased my oncologist has agreed as this is not currently recognised as a standard therapy for LMS.

 

I like to base my treatment choices on scientific information and my decision to try metformin has been made because of various research findings and a scientific hypothesis that suggest it may be of benefit. These include:

• evidence that shows that people taking metformin to treat diabetes appear to have a lower risk of developing cancer than the general population;
• research that indicates metformin has some level of activity against certain types of cancer cells (including sarcoma cells);
• research that shows that taking metformin in combination with some chemotherapy agents may give a better response than the chemotherapy agent alone and, finally,
• a hypothesis that metformin may have some specific value in reducing cancer risk in people with Li Fraumeni syndrome. 

 

When I consider these factors along with the knowledge that metformin is a very widely taken drug with a relatively low risk profile it seems well worth a go.

 

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Earlier this week Katie and I spent a very good couple of days in London. We packed a lot of sightseeing into our visit with trips to Westminster Abbey, Churchill's war rooms, the Cutty Sark, the Royal Observatory and the National Maritime museum.

 

Sometimes I see something in a museum that really captures my imagine. At the National Maritime museum they have an exhibition on Horatio Nelson. I've been interested in Nelson for many years and have read a number of books on his life so I was really keen to see the exhibition. One of the exhibits is Nelson's coat - the one he was wearing as he stood on the deck of HMS Victory at the battle of Trafalgar.

 

The dark blue of the officer's coat was quite possibly what drew the eye of the French soldier who fired the shot that killed Nelson. The musket ball left a small but jagged edged hole in the shoulder of the jacket. From the position of the hole it is clear that the shot was fired from a high angle, looking down on Nelson - probably from the masts of the French ship, Redoutable.

 

I can't think of ever seeing an object more intimately connected to a moment in history or to the personal fate of a man, recording as it does the day of Nelson's greatest victory and the moment he was fatally wounded, the point at which an already much feted British hero became a national legend. I don't think museum exhibits get much better than that!