Friday, 21 March 2014

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.
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.
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.
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.

Friday, 14 March 2014

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.
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.