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Telotristat Ethyl (XERMELO®) – an oral treatment for Carcinoid Syndrome Diarrhea not adequately controlled by Somatostatin Analogues


Telotristat Ethyl is an extremely significant introduction to the treatment of Carcinoid Syndrome diarrhea. It’s the first addition to the standard of care in more than 16 years and the first time an oral syndrome treatment has been developed.  The drug was previously known as Telotristat Etiprate but was changed to Ethyl in Oct 2016. ‘Etiprate’ was previously a truncation of ‘ethyl hippurate’.  The brand name is XERMELO® 

Who is the drug for?

The drug may be of benefit to those whose carcinoid syndrome diarrhea is not adequately controlled by somatostatin analogues (Octreotide/Lanreotide). It doesn’t replace somatostatin analogues – it is an additional treatment alongside (although I have heard of patients in the US being subscribed who are not receiving somatostatin analogue treatment)

Where is it currently approved?

The US FDA approved the drug 28 February 2017. On 19 September 2017,the European Commission approved Xermelo® (telotristat ethyl) for the treatment of carcinoid syndrome diarrhea in patients inadequately controlled by somatostatin analogue therapy after the scientific committee of the EMA (known as Committee for Medicinal Products for Human Use (CHMP)) adopted a positive opinion recommending the approval of Xermelo® (telotristat ethyl) 250 mg three times a day for the treatment of carcinoid syndrome diarrhea in combination with somatostatin analogue (SSA) therapy in adults inadequately controlled by SSA therapy. The Ipsen press release is here.  Clearly some action will be required in EC national countries before the drug becomes available through the appropriate healthcare systems.

Ipsen will pursue a worldwide regulatory plan for marketing authorisation submissions in the territories in which it operates. Once approved, Ipsen will be distributing the drug in all countries less USA and Japan where Lexicon retains the rights. Outside USA and Europe will be constrained by national approval timelines.

How does it work?

In the simplest of terms, the drug is an inhibitor of the enzyme tryptophan hydroxylase (TPH).  TPH is the rate-limiting enzyme in serotonin synthesis which converts tryptophan (an essential amino acid which comes from diet) to 5-hydroxytryptophan, which is subsequently converted to serotonin, one of the main causes of carcinoid syndrome effects including carcinoid heart disease.  The trial data indicates that Telotristat ethyl significantly reduced the frequency of bowel movements. Furthermore, it was also associated with “significantly reduced levels of urinary 5-HIAA“, a marker for systemic serotonin levels, which are typically elevated in severe carcinoid syndrome.  Essentially it works by reducing the manufacture of Serotonin so it’s it may not have any effect on diarrhea not caused by syndrome (i.e. post surgery etc).

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Resources for your perusal:

  • You can read more about the trial data in a summary by Dr Matthew Kulke (Dana Farber) by CLICKING HERE (latest review from 2017 ASCO).
  • There is also an excellent summary in video form by Dr Lowell Anthony (University of Kentucky) by CLICKING HERE. (“any reduction in diarrhea is meaningful“).
  • An excellent technical description of the drug can be found by CLICKING HERE.
  • The detailed output from the trial (results) can be found by CLICKING HERE.
  • Great 2016 article from ASCO (American Society of Clinical Oncologists) can be found by CLICKING HERE.
  • FDA Approval.  CLICK HERE
  • Lex Pharma press release on approval.  CLICK HERE
  • EU Approval (Ipsen Press Release).  CLICK HERE
  • The manufacturer Lex Pharma have established a dedicated site – CLICK HERE

 

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100,000 blog views – thank you!


100,000 blog views!NET Cancer Blog has just recorded 100,000 blog views. I’m extremely excited to have reached this major milestone. However, I’m also really grateful to my followers on this blog site, on Facebook, on Pinterest, on Google+ and on twitter for supporting me through thick and thin. Your engagement with my blog whether a simple ‘like’, a share, a comment, a pin, a tweet, a retweet, an email or via a private message; is not only extremely motivating but also very humbling.

Thank you so much for giving NET Cancer 100,000 pokes in the eye!

Onwards and upwards to 200,000!

Ronny

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I’m only as good as my last scan


“I’m only as good as my last scan”. I received this comment last week in response to one of my posts and I thought it was a very pragmatic thing for someone to say.  The timing is good as I’m off for a CT scan later today 🙂

A NET patient under surveillance has regular tests at determined intervals but the one that is most likely to indicate disease progression, stability or regression is a scan. Markers such as (say) Chromogranin A (CgA) or 5HIAA are clearly useful but in an ongoing surveillance scenario, they alone would not be used as a firm declaration of progression, stability or regression. Every picture tells a story and a scan is normally the confirmation required whether it’s a CT, MRI or PET (etc).

Scans are also important at the diagnostic phase and I’m sure like myself, many people had their first ever scan at this point.  You can have many checks, investigations and tests but for most, the scan is normally the main test that is going to confirm the presence of tumours.  This then leads to further checks to confirm the staging and grading (i.e. a biopsy) and then hopefully, a proper diagnosis.

Looking forward to informing you that I’m as good as my last scan after my visit.  I don’t mind scans.  In fact, I think they are a piece of cake!

Thanks for reading

Ronny Allan

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Dear Doctors – There’s no such thing as a ‘good’ cancer!


Good-BadAt a follow-up meeting during my diagnostic phase in July 2010, the specialist who was investigating my referral condition was clearly suspicious that I had cancer but as the results of my liver biopsy were not yet in, he was not in a position to declare his findings.  However, following my revelation about flushing during this meeting, he immediately guessed the biopsy would confirm Carcinoid (the most common type of Neuroendocrine Tumour (NET)).  I can’t remember much of the conversation but I vividly remember him indicating that of all the issues out there to get, this was one of the better ones.  He was using a meter analogy action with his hands swinging towards the ‘good’ reading!  I hadn’t gone there that day to receive a cancer diagnosis but he was clearly trying to put me at ease and I’m sure it was with the best of intentions.  A little bit of me thinks this scenario is OK but the definition of ‘Good’ before treatment is known might just set expectations too high!

This is a very topical subject on forums and some patients are not happy being told their cancer is a ‘good’ cancer or one of the ‘better’ cancers to get.  Whenever this subject comes up it tends to overlap and extend into associated areas including the deception where people look so well so how can they possibly have a ‘bad’ cancer. If I had an opinion, I would say that no cancer is good but it’s true to say that some are worse than others, e.g. certain cancers will kill lots of people quickly and that’s awful.

Some cancers can be declared in remission after a period but some cancers can stay with you for the rest of your life. Some cancers can result in long-term debilitating side effects. Additionally, the consequences of treatment for certain cancers can be difficult to live with, meaning significant lifestyle changes in the long-term or for life. This is precisely why many cancer patients who live with these ‘consequences’ are angry at the suggestion their cancer is a ‘good one to get’.

Dear Doctors – There’s no such thing as a ‘good’ cancer!  They’re all bad?

Thanks for reading

Ronny Allan

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Running in the Family (Blog 1) – Multiple Endocrine Neoplasia (MEN)


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We all know that Neuroendocrine Tumours (NETs) and their syndromes are complex but there is even more complexity to be found in a group of related disorders known as Multiple Endocrine Neoplasia (MEN).  Until I read up for this post, I hadn’t fully realised how closely related the two conditions are.  I would now recommend that all NET patients should try to understand the basics of MEN and vice versa, particularly as both conditions seem to come with a plethora of endocrine related effects.

Overview

MEN patients will normally have a tumour in at least two endocrine glands – thus the terms ‘Multiple’ and ‘Endocrine’ (tumours can also develop in other organs and tissues).  Neoplasia is just another name for tumour and these can be non-cancerous (benign) or cancerous (malignant) with the potential to metastasize.

MEN syndromes can comprise varying combinations of tumours. So putting the heredity aspects to one side, it’s potentially an extremely challenging diagnostic scenario.  To add to the complexity, some of the associated tumours can be sporadic (non hereditary) classic Neuroendocrine Tumours in various locations.

MEN is actually an umbrella term for a number of types (syndromes) of the disease – MEN1, MEN2 (2a and 2b (2b was formerly MEN3)) and Familial Medullary Thyroid Carcinoma (FMTC). There is a new kid on the block called MEN4 which is extremely rare.  In the most basic of terms regarding tumours, MEN1 seems to be centred on tumours of the parathyroid glands, the pituitary gland, and the pancreas (the 3 P’s) with MEN2 mainly focussed on the thyroid.  MEN4 is similar to MEN1 but caused by mutations in a different gene.

What is particularly distinctive with MEN is that they are inherited disorders (familial).  That means that they can be passed down in families, with each child of an affected parent having a 1 in 2 or 50% risk of inheritance. Consequently genetic screening/testing is normally undertaken in established MEN families and those at risk of MEN.

You may also have heard of other rare NETs with a familial aspect, in particular Pheochromocytomas (adrenal gland tumours) and Paragangliomas (outside the adrenal gland, less common and not all are inherited).  These tend to be grouped under MEN for support and advocacy.

Further information:

I’m grateful to my friend and MEN patient Linda Hageman for supporting my blog activities and also for allowing me to join the AMEN support group to learn more.  This is one of the friendliest and well run support groups I’ve seen.  On this site, you will find Dr Mark Lewis, an Oncologist and MEN patient who supports Linda (who is a Nurse) with a ‘Ask the Doctor’ section on their website.

There are other organisations including one specifically for Pheochromocytomas and I’m grateful to Jennifer Shepard for featuring my nutrition blog series.

Summary

Having just researched the whole subject, I now better understand the basics of MEN and linkages between MEN and NETs.  I now know why there is such a close bond between the patients and advocates of both.  In fact, I have met many patients on forums who are both NET and MEN.

This is a really complex but interesting subject so I’ve suffixed this post ‘Blog 1’ with the intention of exploring further in the coming weeks.

Thanks for reading

Ronny Allan

I’m also active on Facebook.  Like my page for even more news.

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