Monday, 26 March 2012

Opiates, cancer and naltrexone

An interesting paper in Anaesthesiology, (and yes, I know it’s not top of everyone’s reading list), looks at the influence of the mu opiod receptor (MOR) on cancer progression. While you may not have heard of the MOR, you will have heard of the drugs that target this receptor: morphine, fentanyl, heroin and other opiates. These are among the most widely used of pain-relief drugs in current medical practice. In particular these drugs are widely prescribed for cancer patients, either when undergoing surgery or when they are suffering from pain. The question of whether these drugs have an effect on cancer progression is one that is directly relevant to cancer patients here and now. While it has been known for some time that opiate drugs possibly have some indirect effects on disease progression because of the depressive effect on the immune system, the authors of this paper take things a step further and ask whether there is also a direct pro-tumour effect induced by these opiates.

The starting point for this new work is that the authors had worked with the drug methylnaltrexone (part of the same family of drugs as naltrexone), which blocks the operation of the MOR but which does not cross the blood/brain barrier. This means that while methylnaltrexone blocks the operation of opiate drugs, because it doesn’t cross into the brain it doesn’t interfere with the pain relief that opiates are used for. The clinical rationale for using methylnaltrexone is that it doesn’t stop the pain relief, but it does stop constipation and other side effects of opiates.

What the authors discovered was that in working with late stage cancer patients at the University of Chicago they observed several cases of patients treated with methylnaltrexone having longer than expected survival. Like a lot of interesting discoveries, the authors didn’t just put this observation aside, but they followed up on it. There was already evidence that showed that cancer patients who underwent surgery and were treated with opiates had higher rates of recurrence than those that didn’t have opiates. The next step was to follow up with laboratory experiments and the sort of test tube investigations that most researchers start with. Note that here they started with patients and then moved to the test tube.

The test tube results showed that opiates can be pro-angiogenic (they can help tumours sprout the blood supply that they need to survive and prosper), and can switch on a number of other pro-tumour pathways. What’s more, they also showed that it’s not just external opiates, but that internal opiates (normally called endorphins and endomorphins), can similarly act in a pro-tumour manner. And of course we know that stress can release high levels of these natural opiates – and we already know that stress and cancer are inter-connected.

For those of us who have watched loved ones dying of cancer being treated with higher and higher doses of opiates as their condition deteriorated this paper makes for fairly grim reading. It’s also worrying for those who are currently undergoing treatment.

However, the authors point out that the use of methylnaltrexone and naltrexone are now being trailed with cancer patients. And, of course the authors acknowledge the work being doing using low dose naltrexone and alpha lipoic acid – though it needs to be stressed that naltrexone will interfere with the pain relief mechanism of opiates, unlike methylnaltrexone. This is a positive development, and we can only hope that there’s quick progress on this. Methylnatrexone is a licenced drug and is most often used in palliative care to treat opioid induced constipation – if the trials show a positive anti-cancer effect, then perhaps we can expect to see it used more widely in the future.

And for those interested in low dose naltrexone, this latest paper is another small step in the right direction.

The journal paper is available on open access here: http://journals.lww.com/anesthesiology/pages/articleviewer.aspx?year=2012&issue=04000&article=00022&type=abstract

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