Treatment timeline

Over the last week, we have talked (and listened) to many people about Steve's mesothelioma - GP, counsellor, radiotherapist, medical oncologist, clinical oncologist and palliative care nurse aka Macmillan nurse. Most of these sessions have kicked off with a review of Steve's treatment since diagnosis in June 2009; you should see his hospital files - very thick and heavy....

As Steve starts his next treatment regime tomorrow, this seems like the right moment to set it out in a timeline which pulls together all the clinical trials, chemotherapy and medical procedures he has been through since June 2009, together with the related side effects and outcomes.  

Having everything up together in one blog post will be a handy summary for us the next time we have to talk someone through what's happened up to now.  Some readers may find it of interest and assistance if they are contemplating having similar treatment.  If nothing else, it will set the scene for a future blog post and help you understand why Steve feels the way he does right now....

June 2009

• Pleurodesis - draining fluid which had built up between the two layers of the pleura around the lung and sticking the pleura back together using sterile talc. Biopsy taken at the same time. Four days in hospital. Oramorph given for pain relief (and laxative for constipation, a side effect of the pain relief medication) as part of a clinical trial comparing the effectiveness of oramorph to paracetamol for pain relief.  Stitches to the "ports" removed the following week.  Biopsy results showed mesothelioma.

July 2009

• Radiotherapy to the pleurodesis ports using a Linear Particle Accelerator (LINAC) - a total of four visits; one to prepare for treatment and three to zap the ports to reduce the risks of the cancer seeding along the line of the chest drain and endoscopy camera.  Aqueous cream applied to the site of the therapy to reduce soreness. No noticeable tiredness or nausea.

July - November 2009

• Velcade Early Phase Clinical Trial - aka Bortezomib, a biological therapy which inhibits how proteasomes (which control cell growth and function) work - plus cisplatin.  Six 21 day cycles of treatment, with Velcade and cisplatin on day 1, followed by Velcade on its own on days 4, 8 and 11, then a 10 day "rest" period.  Side effects: nausea and vomiting; tiredness; numbness in feet (peripheral neuropathy); taste changes; loss of appetite; anaemia; muscle cramps in joints.  Two enforced breaks in treatment regime due to toxicity - impact on white blood cells - one break of a fortnight, the other of a week.  Nausea and peripheral neuropathy continued post-trial for some time (the latter getting worse before it got better). 

December 2009 - September 2012 : No treatment, disease stable

October 2012- February 2013

• Chemotherapy - pemetrexed (aka Alimta) and carboplatin.  Six 21 day cycles of treatment, with infusions of chemo at the start of each cycle.  The regime was extended by an unplanned break in treatment arising due to appointment problems over the Christmas/New Year holiday.  Side effects: mouth ulcers; fatigue; taste changes; loss of appetite; breathlessness; itchy rash; nose bleeds; anaemia requiring blood transfusions on two separate occasions. Outcome: reduction in pleural thickening after four cycles of treatment, followed by further reduction in pleural thickening after two more cycles of treatment.

March - September 2013: No treatment, disease stable

October 2013: Scan showed disease progression - minor pleural thickening and a new lymph node about 1.5 cm in size noted.  

December 2013: treatment options discussed

January 2014: decision to take part in the VanSel Early Phase drug trial, dose escalation study

February - April 2014

• VanSel - a combination of two biological therapies. Vandetanib - a VEGFR (Vascular Endothelial Growth Factor Receptor) and EGFR (Epidermal Growth Factor Receptor) inhibitor; VEGF is a substance made by cells which helps new blood vesssels develop and grow. VEGR inhibitors stop cancers developing the blood vessels that they need to grow.  Selumetinib is a MEK (Mitogen Activated Kinase) inhibitor which blocks the pathway along which signals are sent to cells telling them to divide and grow.  Steve completed two cycles on this regime - the first cycle was 42 days long, including a "loading" dose of vandetanib every day for 14 days before taking both vandetanib and selumetanib for 28 days.  Cycle 2 was 28 days long, taking both drugs every day.  The trial period was extended with a week's break from treatment as the drugs were affecting Steve's heart rhythm.  Trial resumed on a reduced dose of vandetanib.   Other main side effects: a severe skin rash (mainly on his face, chest and neck) which required steroid cream medication and antibiotic lotion; fatigue; loss of appetite; stomach cramps; sickness; daily diarrhoea; some hair loss; sensitivity to UV light.  Outcome: disease progression over and above trial protocol guidelines

May - August 2014: continued disease progression; cancer has grown through the chest wall and now visible externally as a lump

September - November 2014: 

• AZD 0424 Early Phase drug trial - a 28 day cycle taking the trial drug every day.  The drug is a tyrosine kinase inhibitor which slows down proteins which are involved in cell growth.  Cancer cells have a higher level of these proteins than normal cells. The drug blocks these proteins, preventing the delivery of nutrients to cancer cells. Steve completed the first 28 day cycle, and 21 days of the second cycle before being taken off the drug as the scan showed disease progression and spread to his liver, as well as experiencing pain for the first time from the lump on his chest, which continued to grow in spite of the trial drug. Side effects: fatigue; major hair loss; stomach cramps; loss of appetite. 

December 2014: 

• palliative radiotherapy for pain relief. One "planning session" followed by five consecutive days of treatment starting tomorrow.  We can expect increasing tiredness with each treatment session, peaking about two weeks after treatment around Christmas.  We will also need to slop on the E45 cream to deal with the effects of the radiotherapy on his skin.  There may be some nausea and breathlessness as a result of the beam affecting healthy tissue in the lung and liver, adjacent to diseased areas.  

Overview

After a long period of stability followed by some shrinkage, Steve's mesothelioma has been growing since October 2013. Although he has taken part in two early phase clinical trials this year, the disease continues to progress and spread.  He has recently experienced pain for the first time where the cancer has grown through the chest wall, and there has been significant weight loss. He now weighs about 55 kilos.   He has yet to recover from the side effects of the most recent trial which has left him feeling weak and tired.  It's been a tough year....

What we can expect after radiotherapy and where we go from here is something for blog post in the future.  

What is clear from writing - and now re-reading - this treatment timeline is that Steve has been very brave and endured some horrible debilitating side effects of drug trials over the last 12 months, with no personal benefits.  Each drug trial seems more difficult to endure and bounce back from.  The gaps between drug trials and chemo regimes when we can enjoy a good quality of life are getting shorter.  

The balance of power between Steve and his cancer has shifted over the last year, accelerating over the last 6-8 weeks.  The mesothelioma journey has changed direction and moved on to a new phase.  We are now focussed on thinking about how to manage this for the best.  More of that in a future blog post.  

Thank you so much for all with wonderful messages of support and offers of practical help which are very much appreciated.  

Lastly, a big hug to all the meso warriors around the world, their families and friends, especially Margaret in Canada xxxx

Mixed feelings

The scan results are in....the bad news is that there has been disease progression since Steve started the VanSel drug trial.  

The radiologist looked at a number of circular lesions in the right lung and compared sizes on the scan taken last week with the pre-trial scan in January. The growth was assessed as 26%, which sounds rather alarming. However, due to its nature, diffuse mesothelioma is notoriously difficult to measure accurately, so there is some margin for error in this assessment.

The good news is that in real terms the total (cumulative) increase in tumour size is only 1.7 cm.  We were told that the rate of growth is extremely low when compared to most mesothelioma cases.  The other good news is that the mesothelioma has not spread below the diaphragm or into Steve's bones, and remains confined to the right lung with no new areas showing up on the scan.  

In fact, the bulk of the cancer is still so small that it's difficult to tell the difference between right and left lung when the back is percussed.  It does not sound dull, which is what happens if the meso grows significantly.

Dr Nick examined Steve's chest and advised that the pain he experienced recently in the rib area is nothing to do with the meso - it's just a strain from coughing (which seems to have improved over the last day or two).

Under more recent clinical trial protocols, a 26% increase in tumour size would be considered "stable" disease.   However, the VanSel study started in 2011.  At that time, it was decided that the drug trial protocol would define any growth greater than 20% as disease progression.  Because Steve's has gone over that threshold, the treatment has to stop.  

Having had a couple of hours to digest the news, this outcome has left us both with mixed feelings: disappointment on the one hand and relief on the other.  

Disappointment that the combination of drugs has not stopped Steve's meso in its tracks and that, for him, its not the magic bullet to cure the disease (although it may work better on someone else).  It's also possible that the benefit of taking the drugs has yet to manifest themselves in Steve's case - there may be a delayed response, or it may have slowed what would otherwise have been more rapid growth. The bottom line is that we don't know.

But now that the decision about continuing the trial has been taken out of our hands, it feels like a weight being lifted off our shoulders.  Steve had said that even had there been a reduction in tumour size, deciding whether or not to carry on with treatment would still have been a tough call. Living with the side effects of the trial drugs, especially daily diarrhoea at unpredictable times, has keep us housebound for the last couple of months...Steve has felt too vulnerable to venture far from a lavatory. It's difficult to imagine enjoying a life like that in the long term, at least not at the moment while he is otherwise asymptomatic.

Steve remains under the care of the Early Phase Clinical Trials Unit for another four weeks and will go back at the end of that time for a post-trial check up, including blood and urine tests, temperature, pulse, blood pressure, weight and ECG. He won't need another scan having had one relatively recently, or another eye test - that was done this afternoon.  

Dr Nick will tell Steve's consultant what's happened, and he will be put back in "the system" and followed up in clinic, as normal.  However, Steve's name will be put on the waiting list for any suitable Phase 1 trials that come up in future. Because he is relatively fit (aside from the mesothelioma) he is considered an ideal candidate.  We were also told that there are other trials coming through in Oxford, so maybe he won't have to wait too long if his condition worsens.

In the meantime, he's looking forward to getting the drugs out of his system and returning to "normal" over the next few weeks.  Its a relief to know that from now on, our lives won't be regulated by dose and fasting times; we can once again enjoy the pleasure of a late breakfast and an evening meal without worrying about finishing food and drink by 9.30 am/pm.  Meals out with family and friends are on the cards again as and when Steve's gut gets back to normal, and we can think about going away for a long weekend or short break, which we have both missed this year.

And now, for the first time in 2014, we have the prospect of not going to hospital for a whole month!  The team on the Early Phase Clinical Trials Units are great, but it will be nice not to have to see them once or twice every week, as we have been going since January when the pre-trial tests started...With blue skies and sunshine, it almost feels like the start of the long school holiday.... 

....and Easter will be extra special this year!   

a birthday, a blip and another bereavement....

First of all, thank you for Steve's birthday cards, messages and good wishes.  It was a low key day, with phone calls from our children, a special evening meal and a nice bottle of vintage fizz at home providing some highlights.  We'll have a proper celebration when Steve is feeling a bit better.  

The antibiotic tablets and cream seem to be making a small difference to Steve's skin on his face, neck and chest. Although it's still a long way off "normal" at the moment, there does seem to be a slight improvement day on day. However, still not enough at the moment to feel comfortable about going out in public unless he has to, like today - hospital day.  

We were all geared up for another 12 hours in the clinical trials unit - newspapers to read, a couple of films to watch on the laptop, a cushion to support my lower back (visitors chairs not good in this respect, especially if you spend the best part of twelve hours or so sitting in them!). 

Steve's bloods were taken for testing, along with blood pressure - still high, but not as high as last week - plus ECG, which measures the electrical activity of the heart over a period of time.  Steve had three measurements taken at five minute intervals.  We thought nothing more about it at the time, just waited for Dr Nick to arrive to give Steve a physical examination.

We know that some patients treated with vandetanib alone have experienced changes in the electrical activity of the heart, usually without experiencing any symptoms.  As a result, patients on the VanSel drug trial have frequent ECG assessments to ensure that any changes are managed by the doctor and do not become serious, as they can be linked to a condition called Torsade de Pointes, which can be life threatening. 

Each heartbeat is mapped by the ECG machine as five distinct electrical waves called P, Q, R, S and T.  The part of the pattern from Q to T represents the electrical activity of the heart's lower chambers, or ventricles.  When the QT interval is abnormally long, it means the heart cells in the ventricles are taking longer to recharge after each heart beat.  This can upset the careful timing of the heartbeat and may trigger an abnormally fast or irregular heart rhythm which can result in dizziness, light headedness, chest discomfort and shortness of breath or fainting.  

We were told this morning that Steve's "normal" QT measurement is longer than average and has been getting a little bit longer at every ECG.  Today, it measured 182.  The drug trial protocol is that a patient's QT interval should not go above 180 for their safety and to avoid the sort of things described above happening.  

As a result of his prolonged "QT" interval, Steve will stop taking the trial drugs for a week in the hope that his heart's rhythm will return to normal. However, he can continue to take the antibiotics which show signs of helping his skin improve.  Although the rest of his blood tests were OK, they think he would benefit from some extra magnesium. Amongst other things, magnesium plays a role in the transport of potassium ions across cell membranes, a process which is important to normal heart rhythm - so that should help his heart beats return to (what for Steve) is normal.  

Reading what I have just written sounds a bit scary. However, Dr Nick pointed out that in the drug trial everyone in the same cohort gets the same dose, regardless of their height, weight, metabolism etc.  There is bound to be some variation in how people react as the dose is not tailor made for each individual. Hence the regular and frequent monitoring to ensure that everyone stays safe.

With no trial drugs to take for a whole week, we are off the hook in terms of the strict mealtimes (and Steve's fasting) regime, we've grown accustomed to over the last four weeks. It will be strange!

I will now have to cross off the hospital dates on the calendar - everything will be shunted back at least a week.  We'll see how the next seven days go and take it from there....

We came home to more sad news that another meso warrior died today. It's less than two weeks since Ian, Grace and one of their sons, met up with fellow meso warrior Mavis and Ray for coffee in Kent.  Ian's sudden deterioration has come as a shock to all.  

Our hearts go out to his lovely wife Grace, their sons - the youngest of whom is only 11 years old - and Ian's family and friends  xxx

tests, tests and more tests...

After having his "baseline" scan last Friday, we were back in hospital again today for Steve to be tested to make sure he's fit enough to start the VanSel1 drug trial next week.  

It's a very thorough procedure, partly to make sure he meets the trial eligibility criteria and partly to have a baseline against which any changes to his body arising from the drugs or their side effects can be measured.  

So - what was involved?

• Physical examination, including height and weight measurements
• Vital signs (blood pressure, pulse rate and temperature)
• Blood tests 
• Urine tests
• ECG  (heart trace - three tracings over 5-10 minutes)
• Echocardiogram (a bit like an ultrasound scan, with jelly on the chest )
• Eye test - to rule out any eye conditions that might be made worse taking the study treatment

The echocardiogram was carried out at a different Oxford hospital and the eye test by a local optician, but luckily we had time to go home for lunch in between.  While we were at home, Julianna the trial nurse phoned to say that Steve's potassium levels were spot on.  No need to go back to the Cancer Centre for a top up, which would have been necessary had they been too low for the trial.  Eating all those bananas has clearly paid off!

The tests themselves were relatively straightforward.  It was only the very thorough eye tests, which involved dilating the pupils, which caused any problems.  Even though it was cloudy, the brightness on going outside after the test hurt Steve's eyes.  But he was back to normal by the time we arrived home....Must remember to take sunglasses or a baseball cap next time to shade his eyes! 

Only when they check the results of all these tests will we know if Steve can take part in the trial. 

Now we wait....

Baby steps forward

This time last week, we had paddled home through the floods after our visit to the hospital to discuss treatment options with Steve's consultant and were feeling optimistic! A lot of water has, quite literally, gone under the bridge since then...

River levels in Oxford peaked last Thursday and have since being going down very slowly. Although the park at one end of our street remains mostly under water, the main road at the other end of the street - which had been closed due to flooding - eventually reopened and we were able to go out in the car on Monday to re-stock food and other essential supplies.

As anticipated, many of the things we had been storing in a rented garage a few streets away have had a good soaking, so a lot will have to be thrown out/recycled in the coming weeks when we have the time, energy and inclination to get our hands dirty.  In the meantime, it can carry on drying out...

The reopening of the main road meant that postal deliveries have resumed.  At long last, a camera that I won in a competition back in September has arrived, together with a camera case by way of apology for the delay.  Thank you Olympus - I look forward to playing with the new kit! However, there was no sign of the information sheets about the VanSel drug trial Steve hopes to take part in, which was making us a little anxious.

Then yesterday afternoon there was a phone call from the hospital saying the information was now available - did we want to collect it?  Yes please!  The timing of the phone call was fortunate.  Shortly after, the electricity supply which had cut out several times over the previous two days, went off again and stayed off....a victim of the flooding and high water table levels.  Thank goodness we had a large supply of candles, a big new box of matches, a film downloaded on to a fully charged iPad, plenty to eat and a bottle of wine.  After the initial frustration, it turned out to be quite a romantic evening!

Power supplies were restored about 8 o'clock this morning, just in time for breakfast.  Apparently the fault causing the problem has been found and the engineers will be working on a permanent fix tonight.  We are bracing ourselves for another power cut this evening, but hopefully that will be the end of it...

We have been to the hospital today and collected the information sheet about the drug trial which I scanned quickly on the way back home. I confess that when faced with a long list of possible side effects in black and white, the prospect of going back into treatment looses some of its appeal.  

In particular, the trial drugs make skin very sensitive to UV light so anyone taking part has to cover up as much as possible and use a minimum of factor 50 sunscreen on exposed parts when outdoors, even in winter.  Steve is not a great one for sunbathing, but neither is he a great fan of slopping on sunscreen, so that would be a challenge for him.  

Other side effects are similar to those experienced with previous chemo regimes - not things to look forward to...On the other hand, not every one experiences the same effects so until treatment begins, we won't know how it will be...

We'll read through the fact sheets in detail tonight and if Steve still wants to take part, he'll phone the hospital tomorrow to arrange an appointment to  deliver the consent forms and get dates for the extensive tests that have to be carried out to make sure he's well enough to take part in the drug trial.  Then we wait for the results....so it's baby steps forward....

It was strange going back to the Clinical Trials Unit today. The last time we were there was some four years ago, when Steve took part in the Velcade drug trial. The Cancer Centre had only just opened then. The NHS Trust had commissioned "uplifting" artwork and we were delighted to see one of my photos on display in the room where Steve had treatment several times.  We noticed today that it's still there, and still looks good.  The doctor we saw today was also impressed when we pointed it out to him!

With the possibility of another power cut tonight, I think I ought to post this now rather than wait until photos have been downloaded.  Time to take a deep breath before reading the information sheets and facing the demons of fatigue, mouth sores, skin rashes, diarrhoea, blurred vision, loss of appetite and all the other stuff that may be waiting for Steve in the next few months, assuming he signs the form and passes the tests to get on the trial.  Here we go again...probably, maybe....