Tag Archives: chemotherapy

T cells bouncing back after chemo good sign for immunotherapy success

Mesothelioma patients whose T-cell counts bounce back quickly after a round of chemotherapy have a better chance of survival. They are also most likely to benefit from the addition of immunotherapy.

That’s the conclusion of a British study looking for prognostic indicators in mesothelioma patients undergoing a combination of chemotherapy.

hemotherapy is the most common first-line treatment for mesothelioma. It involves flooding the body with a drug or combination of drugs designed to destroy cancer cells. Immunotherapy involves “programming” the immune system to recognize cancer cells as foreign invaders and attack them the way they might attack bacteria or viruses.

To devise a prognostic method for mesothelioma patients who might undergo both types of therapies, the scientists looked for longitudinal changes in peripheral T-cell subsets in 40 patients with malignant mesothelioma or advanced non-small cell lung cancer. All of the patients were receiving platinum-based chemotherapy.

The study found the T-cells of all patients were almost entirely knocked out by the 8th day following chemotherapy, but most bounced back quickly and even passed baseline levels. Regulatory T-cells (Treg) have immunosuppressive properties and are the cells responsible for maintaining order in the immune system. In the study, Treg cells were most profoundly depleted by chemotherapy. Mesothelioma patients whose CD8(+)T-cells bounced back the most after a cycle of chemotherapy had the greatest overall survival. A bigger ratio between CD8(+) T-cell to Treg proliferation was also predictive of better outcomes.

Because the effectiveness of immunotherapy depends on the depletion of Treg cells (because of their immunosuppressive properties) and the strength of the T-cell pool, the researchers theorize that those who showed the most dramatic changes in these two cell types areas are the ones most likely to benefit from a combined chemotherapy/immunotherapy approach.

 

good and bad news from recent chemotherapy trials

Three new published studies contain a mixed bag of findings on the effectiveness of chemotherapy for mesothelioma.

In  a study designed to help doctors predict which mesothelioma patients will respond to pemetrexed-based chemotherapy, results were promising. Pemetrexed works, in part, by preventing mesothelioma cells from synthesizing several key enzymes, including thymidylate synthase (TS). Scientists found that, as predicted, high levels of TS during therapy were a sign the drug was not working .

In a separate cellular process, pemetrexed is converted into a more effective form by folylpoly-y-glutamate synthetase (FPGS).  In the same study, patients who had high FPGS expression saw better mesothelioma tumor response to pemetrexed.

While there is still no standard second-line chemotherapy treatment for mesothelioma, a Phase II study in Australia suggests that the oral chemotherapy drug sunitinib might be an option for some. Fifty-one mesothelioma patients received two cycles of sunitinib between July 2006 and December 2009. Six patients (12%) showed a partial response to the drug and 34 (65%) had stable disease. The team concludes that “Sunitinib has activity in a subset of patients with pretreated malignant pleural mesothelioma” and recommends further study of sunitinib.

The news was not as good for the drug bortezomib. A single-arm Phase II trial on bortezomib as a first- or second-line therapy found a partial response in only one out of 23 patients enrolled.  Preclinical tests on bortezomib had looked promising, but in light of the Phase II trial results, the UK-based research team concluded that the therapy “exhibits insufficient activity to warrant further investigation in unselected patients with mesothelioma”.

All three studies appear in the most recent issue of the Journal of Thoracic Oncology.

Mesothelioma treatment developments in the US

Always interesting to see what else is being developed worldwide, the US has led a lot of the treatments and just published a recent update regarding heated chemotherapy during surgery. This multi-pronged treatment is meant to reach cancer cells that surgeons can’t easily remove. This form of treatment is particularly useful when treating peritoneal mesothelioma, a rare cancer that affects the lining of the abdomen, as the chemotherapy drugs are heated and used to bathe the abdominal cavity.

 

In an article published in the New York Times on August 12, 2011, heated chemotherapy was described as the most aggressive form of cancer treatment possible. In the article, Dr. Paul Sugarbaker, a leading proponent of hyperthermic chemotherapy, as the therapy is also known, said that it is common knowledge among doctors that cancer cells cannot withstand as much heat as healthy cells. Applying the chemotherapy directly over the tumors should be more effective than administering the medication through the bloodstream.

However, the treatment also has critics who question the therapy’s benefits, despite the fact that an increasing number of American hospitals are offering it as treatment for mesothelioma and a variety of other cancers.

Critics believe that studies of hyperthermic chemotherapy were slanted towards patients with less severe cases of mesothelioma and, therefore, garnered far better results than if they had been conducted with your average mesothelioma patients.

Haven’t heard from anyone if this is offered in the UK .

 

After chemotherapy- day 1

Appreciate that technically it is really day 38 or something, but today really did feel like a first day. Made the most of the good weather by packing a very small picnic ( fitted in a bicycle bum bag) and heading off to Richmond Park on the bicycles.

Really took time to explore the park, cycling through the centre and then round the periphery , in total around 18 miles, but also included two hills, so we were both seriously out of breath. Got his lungs working , although at one point , he said never mind the lungs , what about my heart. Still we managed to cycle the whole way , even though we did get overtaken by other cyclists on the way up .

Picnicked at Pen Ponds, watched the herds of deer wandering along under the trees near the cycle path and generally thought all right with our world.

Hopefully he managed to get a bit of a suntan, even so , he is almost visibly getting stronger each day. His taste buds are coming back as is his strength , which is making him  so much more positive.

Still have the traces of chemo , with really pink feet and numbness in his finger tips , will check out the new painkillers next week and see if they help with the after effects of the surgery, it’s tolerable but would be better if he could control it, providing of course side effects aren’t too great.

Here is too many more good days

no chemotherapy tomorrow- hurray!!

And the good news is , day 21 but nothing due tomorrow, first time in months . Time now to really start to recover from the treatment if not the cancer. Good news is  out on bicycle yesterday and today. 6 miles yesterday and 10 miles today , along the towpaths of the Thames.

Gets out of breath quickly and tends to feel the effects of the cycling with increased soreness , but definitely worth the effort as gives him a definite boost. Now we just need a good news scan and his hair to regrow!!

Started my one week cookery course today –  whole day at school and brought home chopped vegetables and houmous. Shows he is feeling better as he offered to cook dinner , lucky really , means he can have stir fry tomorrow ( with beautifully chopped vegetables of course )

Tomorrow all the drugs stop – end of the folic acid and the levemopromazine, so back to basics and an end to drug charts and side effects. Plus the sun was out today , so all in the garden blooming ( with a little watering of course). One really nice place to sit amongst the flowers , but you have to be quick  to sit there……….

Chemotherapy – anti nausea drug options

One of the biggest factors in getting through this treatment , is the success , or otherwise in controlling nausea. Anyone who has ever experienced sea- sickness, knows just how depressing and debilitating it can be. Now imagine  sea sickness for weeks , then just when you start to feel better , going right back to square one- voluntarily!!

The good news is  lots of drug options to help, the bad news is everyone seems to react differently , so there is no one right answer. At first weren’t sure just how much it could be improved and thought that as long as he wasn’t vomiting constantly , it was as good as we could hope , but in fact , over the past few weeks have controlled it to a much better level, such that whilst still nauseous at times, never stops him eating and never results in actual sickness.

Over the past few months , this is our experience of the following  drugs

Steroids – dexamethasone , starts day before each treatment and continues for four days afterwards. These have proved really effective , seem to stimulate his appetite and keep nausea at bay really well. Their main downside is they do make him a bit hyper at night and disrupt his sleep as well as increasing restless legs syndrome.

Ondansetron – this is given intravenously during the day the chemo is administered, it appears to target nausea actually caused on the day and its immediate aftermath, apparently it works best in conjunction with steroids  and is a serotonin blocker. Again this seems to have been  really effective as nausea reduced in those first couple of days.

Metaclopramide – this has been the mainstay of our anti nausea controls  , normally starts day after the chemo treatment and is taken for round 5 – 9 days, it works by blocking the vomiting centre and encourages the stomach to empty , so that it gets rid of the heavy feeling you have when you feel sick. This had a lot of experimentation. At first we just took along with the steroids and stopped on the same day – this was a bad move as immediately started being sick the day after they stopped and although restarted them , never really got rid of the nausea at all. Also found  it was really bad first thing in the morning and during the night, when he was constantly waking up feeling sick and having to run to the loo, often just dry retching. As one of its common side effects is restlessness and muscle spasms , they didn”t help with the sleeping either ( not everyone gets same side effects of course )

Cyclizine – at round 2 when we said how bad the nauses was, they also prescribed this drug and suggested the metaclopramide was taken in addition for the first seven days. This is an antihistamine often used for sickness that combines well with other drugs – this one one didn’t work at all for him, still had sickness after the steroids stopped and same problems at night.

Levemopromazine ( Nozinan) – round 3 and  a new prescription to add to our growing medical chest . Again in combination  with metaclopramide, this stopped the dry retching in the morning , although had terrible effects on his moods ,  he veered between aggression and zombiedom.

Round 4 – here we found taking  metaclopramide for 9 days , but restricting it to morning and afternoon, at double the initial dose after discussions with the oncologist ,  reduced restless leg syndrome side effect and stopped actual vomiting but still left him feeling very nauseous for those first five days after the steroids stopped.

Round 5 – still taking the metacopramide, twice a day for the first 7 days, but supplemented with  levemopromazine at night . Strangely this time, the mood swings are much less, still can be a bit dopey during the day , but worth it as totally removes nausea at night , stops the dry retching and improves his sleep. Have kept this one going for a full two weeks and is best he has felt . looking to stop this now and go to no drugs other than the Folic Acid for the final week.

Fingers crossed same combination works as well  for round 6 .

Getting to grips with chemotherapy

Had a really good couple of days, mainly because he has been able to get some reasonable sleep. This means he feels so much better during the day, no restless legs , no nausea and very few aches and pains. Still very lethargic and tired , so the afternoon black and white film has become a staple of the day , along with midsommer murders , but in his own words ” its taken a few months but think I’ve got to grips with chemotherapy”.

No more talk about not doing number 6 , now we just need to make sure blood count OK for number 6 on the 22nd June. Luckily not one of the prospective tube strike days which would have really messed us up – we thought we’d have to book an hotel the night before.

Talk is starting to turn to what he is going to do in terms of work , where we can go in August as we both need a break. How well he might be in July, so that we can do something. Have had my part time job offer through starting 1st September , so artmake the most of July and August.