Chemo or not Chemo – that is the question 


I’m continually seeing certain drugs for treatment of Neuroendocrine Tumours (NETs) described as chemotherapy. I think there must be some confusion with more modern drugs which are more targeted and work in a different way to Chemotherapy.

I researched several sites and they all tend to provide a summary of chemotherapy which is worded like this:  Chemotherapy means:

a treatment of cancer by using anti-cancer medicines called cytotoxic drugs.  Cytotoxic medicines are poisonous (toxic) to cancer cells. They kill cancer cells or stop them from multiplying. Different cytotoxic medicines do this in different ways. However, they all tend to work by interfering with some aspect of how the cells divide and multiply. Two or more cytotoxic medicines are often used in a course of chemotherapy, each with a different way of working. This may give a better chance of success than using only one. There are many different cytotoxic medicines used in the treatment of cancer. In each case the one (or ones) chosen will depend on the type and stage of your cancer. Interestingly, there are several statements along the lines of ‘Cytotoxic medicines work best in cancers where the cancer cells are rapidly dividing and multiplying’, a key issue with lower grade NETs.

Well known chemotherapy treatments for NETs include (but are not limited to): Capecitabine (Xeloda), Temozolomide (Temodal), Fluorouracil (5-FU), Oxaliplatin (Eloxatin) Cisplatin, Etoposide (Etopophos, Vepesid), Carboplatin, Streptozotocin (Zanosar). Some of these may be given as a combination treatment, e.g. CAPecitabine and TEMozolomide (CAPTEM).

In the past, any medication used to treat cancer was regarded as chemotherapy. However, over the last 20 years, new types of medication that work in a different way to chemotherapy have been introduced. Many of these new types of medication are known as targeted therapies. This is because they’re designed to target and disrupt one or more of the biological processes that cancerous cells use to grow and reproduce.  They are classed as biological therapy.  In contrast, chemotherapy medications are mostly systemic in nature and designed to have a poisonous effect on cancerous cells, thus the term ‘cytotoxic’.

The following well known NETs treatment are not really chemotherapy and describing them in this way is not only misleading but may actually cause alarm to other patients. Furthermore, if you check any authoritative NET Cancer specialist or advocate organisation; any general and authoritative cancer site or the manufacturer’s websites; you will not see the drugs below listed within the term chemotherapy.

Somatostatin Analogues e.g. Sandostatin (Octreotide), Somatuline (Lanreotide).  Although these drugs have an anti-cancer effect for some, they are in fact hormone inhibitors and are therefore a hormone therapy.

Everolimus (Afinitor).  This is a targeted biological therapy or more accurate a mammalian target of rapamycin (mTOR) inhibitor. It is a type of treatment called a signal transduction inhibitor. Signal transduction inhibitors stop some of the signals within cells that make them grow and divide. Everolimus stops a particular protein called mTOR from working properly. mTOR controls other proteins that trigger cancer cells to grow. So everolimus helps to stop the cancer growing or may slow it down.

Sunitinib (Sutent).  This is a targeted biological therapy or more accurate a protein (or tyrosine) kinase inhibitor. Protein kinase is a type of chemical messenger (an enzyme) that plays a part in the growth of cancer cells. Sunitinib blocks the protein kinase to stop the cancer growing. It can stop the growth of a tumour or shrink it down.

I can only speculate why some of the confusion exists but I do have some personal experience I can quote too. Firstly I believe it could be easier for some people to describe the new agents as ‘chemotherapy’ rather than explain things such as somatostatin analogues, ‘mammalian target of rapamycin (mTOR) inhibitors’, protein kinase inhibitor or angiogenesis inhibitors. Another reason could be that health insurance companies do not have the correct database structures in place on their IT systems and therefore need to ‘pigeon hole’ drugs into the closest category they can see. Often this is chemotherapy and this only adds to the confusion. In the days when I had health insurance, my Lanreotide injections were coded as chemotherapy on all my bills. I challenged it and this is how they explained the issue.

I’m sure there’s other reasons.

Thanks for reading

Ronny

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Remember ….. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life!

Neuroendocrine Cancer – Exciting Times Ahead!  

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In the last 12-24 months, there seems to have been announcement after announcement of new and/or upgraded/enhanced diagnostics and treatment types for Neuroendocrine Cancer.  Scans, radionuclide therapies, combination therapies, somatostatin analogues, biological therapies, etc.  Some of the announcements are just expansions of existing therapies having been approved in new (but significant) regions. Compared to some other cancers, even those which hit the headlines often, we appear to be doing not too badly.  However, the pressure needs to stay on, all patients need access to the best diagnostics and treatments for them; and at the requisite time.  There’s even more in the pipeline and I’m hoping to continue to bring you news of new stuff as I have been doing for the last year.

Some of these new diagnostics and treatments will benefit eligible patients who are in diagnosis/newly diagnosed and also those living with the disease. As we’re now in our awareness month, let’s recap:

Scans

Many NET Patients will undergo a nuclear scan to confirm CT results and/or to detect further neuroendocrine activity.  Basically, a nuclear substance is mixed with a somatostatin analogue, injected into the patient who is then scanned using a 360-degree gamma camera.  As gamma cameras are designed to show up radioactive activity; and as Neuroendocrine Tumour cells will bind to the somatostatin analogue, it follows that the pictures provided will show where Neuroendocrine tumours are located.  Many people will have had an ‘Octreotide’ Scan (or more formally – Somatostatin Receptor Scintigraphy) which is still the gold standard in many areas. The latest generation of nuclear scans is based on the platform of the Gallium (Ga) 68 PET Scan. The principles of how the scan works is essentially as described above except that the more efficient radioactive/peptide mix and better scan definition, means a much better picture providing more detail (see example below). It’s important to note that positive somatostatin receptors are necessary for both scans to be effective. Europe and a few other areas have been using the Ga-68 PET scans for some time (although they are still limited in availability by sparse deployment). The latest excitement surrounding this new scan is because they are currently being rolled out in USA.  Read about the US FDA approval here.  You may hear this scan being labelled as ‘NETSPOT’ in USA but this is technically the name for the preparation radiopharmaceutical kit for the scan which includes a single-dose injection of the organic peptide and the radionuclide material. Take a look at a comparison of both scans here:

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Octreoscan output vs Gallium 68 PET output

This slide from a recent NET Research Foundation conference confirms the power of more detailed scanning.

Peptide Receptor Radionuclide Therapy (PRRT)

Similar to above, this treatment has been in use in Europe and other places for some time but is also to be formally deployed in USA if, as is expected, the US FDA approval is positive at the end of this year (Read here).  In the most basic terms, this is a treatment whereby a peptide is mixed with a radionuclide and is drip fed over a number of treatments (normally up to 4 spaced out over a year). The concept of delivery of the ‘payload’ to the tumours is actually very similar to the preparation for a radionuclide scan as described above, the key difference is the dosage and length of exposure whilst the tumours are attacked. Once again, receptors are important. The NETTER series of trials showed good results and this is an excellent addition to the portfolio for those patients who are eligible for this treatment. Fingers crossed for the US FDA announcement due by the end of this year.  Also fingers crossed that PRRT returns to the NHS England & Wales portfolio of available treatments next year.  The Carcinoid Cancer Foundation has an excellent summary of PRRT here.

PRRT and Chemo Combo

Whilst on this subject, I also want to highlight the innovative use of combo therapies in Australia where they are combining PRRT and Chemo (PRCRT).  I blogged about this here:

PRRT CAPTEM

Somatostatin Analogues and their Delivery Systems

Somatostatin analogues are a mainstay treatment for many NET Patients.  These drugs target NET cell receptors which has the effect of inhibiting release of certain hormones which are responsible for some of the ‘syndromic’ effects of the disease.  Again, receptors are important for the efficacy of this treatment.  You can read the ‘geeky’ stuff on how they work here.  These drugs mainly comprise Octreotide (provided by Novartis) and Lanreotide (provided by Ipsen). The latter has been around in Europe for 10 years and was introduced to North America earlier this year.  Octreotide has been around for much longer, almost 17 years.  When you consider these peptides have also been used to support nuclear scans that can detect the presence of tumours; and that studies have shown they also have an anti-tumour effect, they really are an important treatment for many NET Patients.  I’ve blogged about new somatostatin analogues in the pipeline and you can read this here.  This blog also contains information about new delivery systems including the use of oral capsules and nasal sprays (…….. very early days though).

Treatment for Carcinoid Syndrome

telotristat-etiprate-clinical-trial-serotonin-as-a-key-driver-of-carcinoid-syndrome

For maintenance and quality of life, the release of a Telotristat Ethyl for Carcinoid Syndrome is an exciting development as is the first new treatment for Carcinoid Syndrome in 17 years.  This is a drug which is taken orally and inhibits the secretion of serotonin which causes some of the symptoms of the syndrome including diarrhea.  It must be emphasised it’s only for treating diarrhea caused by syndrome and might not be effective for diarrhea caused by other factors including surgery.  Read about how it works and its target patient group in my blog here.

Oncolytic Virus

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The announcement of a clinical trial for the Oncolytic Virus (an Immunotherapy treatment) specifically for Neuroendocrine Tumours is also very exciting and offers a lot of hope. Click the photo for the last progress update.  

Everolimus (Afinitor)

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Earlier this year, AFINITOR became the first treatment approved for progressive, non-functional NETs of lung origin, and one of very few options available for progressive, non-functional GI NET, representing a shift in the treatment paradigm for these cancers.  It’s been around for some time in trials (the RADIANT series) and is also used to treat breast and kidney cancer.  It’s manufactured by Novartis (of Octreotide fame).  It has some varying side effects but these appear to be tolerable for most and as with any cancer drug, they need to weighed against the benefits they bring.

In technical terms, AFINITOR is a type of drug known as an ‘mTOR’ inhibitor (it’s not a chemo as frequently stated on NET patient forums).  Taken in tablet form, it works by blocking the mTOR protein. In doing so, AFINITOR helps to slow blood vessels from feeding oxygen and nutrients to the tumour.

Check out Novartis Afinitor website for more detailed information.  There’s an excellent update about AFINITOR rom NET expert Dr James Yao here.  The US FDA approval can be found here.

Summary

………. and relax!   Wow, I’ve surprised myself by collating and revising the last 12-24 months.  Dr James Yao also agrees – check out his upbeat message in the attached 2 page summary.  You may also like another upbeat message from Dr Jonathan Strosberg by clicking here.

Neuroendocrine Cancer – who’d have thought it?  ….. a bit of a dark horse.

Thanks for reading

Ronny

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

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Remember ….. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life!

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