There’s been a lot of action in the area of what is termed Gastro-Entero-Pancreatic Neuroendocrine Tumors (GEP-NETs). It can therefore sometimes appear that Lung NETs are the poor relation. There are certainly some unmet needs in this area of the anatomy including a lack of research. Thus far, no prospective trials specifically for patients with lung NETs appear to have been reported.
However, there has been some recent movement. Last year, the use of Afinitor (Everolimus) was approved for progressive, non-functional NET of GI or Lung origin.
SPINET Trial for Lung NETs
In late 2016, I tipped you off about an Ipsen sponsored trial for Lung NETs involving Lanreotide (Somatuline). SPINET is a Phase 3, prospective, multi-center, randomized, double-blind, study evaluating the efficacy and safety of Lanreotide plus “Best Supportive Care” (BSC) versus placebo plus BSC for the treatment of well-differentiated, metastatic and/or unresectable, typical or atypical lung NETs. The aim of the SPINET study is to evaluate the safety and antitumor efficacy of Lanreotide 120 mg in patients with advanced lung NETs. I suspect that many Lung NET patients are already receiving somatostatin analogues (Octreotide/Lanreotide) but prescribed only for syndrome/symptom control.
SPINET is now recruiting in many locations (see below).
The countries involved in the SPINET trial are as follows (in case my post goes out of date – see the latest update to the trials document here). Please also check the inclusion and exclusion criteria.
USA, Austria, Canada, Denmark, France, Germany, Italy, Netherlands, Poland, Spain, UK.
In addition to the trial document linked above, you can read more about the SPINET trial here with commentary from a well-known NET Specialist – Dr Diane Reidy-Lagunes, who is the principal investigator for the trial.
How do I get on the trial?
You may be interested in this organisation – Trialbee. They are a company helping Ipsen to raise awareness of the SPINET trial using a cloud based platform to connect patients, investigators and sponsors (I’ve authenticated their participation with Ipsen). There is no fee for using their services. There’s a useful questionnaire which can help you decide if this trial is for you – here.
Please note, if you are concerned about participating in clinical trials, you should always consult your specialist for advice.
If you are a patient advocate or an advocate organisation, please share with your communities in order that Lung NET patients are at least made aware of the trial.
I think after 105 injections (as at 26th November 2018), I think it’s safe to say I’m now ‘at home’ with Lanreotide (Somatuline Autogel – Somatuline Depot elsewhere).
I was fortunate enough to actually have the injection ‘at home’ via an insurance policy for the first 4 of the years of my treatment. That was really handy because it was informal, chatty, and I had excellent ‘continuity of service’ with the same nurse administering 80-85% of those 54 injections. I only had 3 other nurses over that period covering my local nurse’s holiday etc.
When I retired from work, I then had to travel to my local hospital and take my turn amongst the ‘great unwashed’. Don’t get me wrong, I have the greatest respect for the UK NHS. However, it’s also true to say my monthly ‘butt dart’ suddenly became more of a conveyor belt feeling, less chatty but in the main, the continuity effect I enjoyed previously was thrown right out of the window. I had some superb injections but I also had some ‘not so superb’ ones. There was very little continuity as my 33 hospital administered injections were carried out by 17 different nurses.
If I had to list 6 common discussions between NET patients, issues with their injections of somatostatin analogues would almost definitely be on the list. Common administration problems with Lanreotide include untrained administrators, fridge problems, incorrect injection site, pinching instead of stretching, plunge speed, painful injections and many others. All of these issues can be linked to training and continuity. One thing NET patients like is an expert injection by the same person if at all possible. It’s also true to say that these issues can cause some anxiety amongst patients leading up to and during the procedure.
I was therefore delighted to be signed up this week for a service in UK called HOMEZONE+ whereby a trained nurse will come to my house and administer my injection. Although it’s been available for some time, this element of the service has not been particularly well publicised. The drug will arrive a few days prior and be stored in my fridge ready for the injection day. For those worried about transport, the drug arrives by courier in a refrigerated vehicle. The service is provided by a third-party via NHS, at no cost to the NHS or the patient, as it is a service funded by Ipsen Ltd.
Now …… I got wind of this service 6 months prior to starting but it took me sometime to discover what it was all about, despite a lot of ‘digging’. I had previously heard of other elements of this service whereby the drug is delivered directly to patient’s house for self injection, injection by a trained carer or for injection at a third-party site such a local GP (PCP). However, the service I’ve signed up for is none of those, this is a service where a trained nurse will come to my house and administer the injection. Happy days. Royal Bournemouth Hospital is actively promoting the scheme to patients being administered with Lanreotide.
But ….. It was also suggested to me that not all hospitals are making the service available. If this of interest to other UK patients, I suggest you initially make contact with your specialist nurse or doctor and enquire (….. and if it was me, I would ask why not if they’re not making it available!). I’ve probably documented all I know but happy to chat more with UK patients about the scheme – you can message me here: Message Ronny Allan
What about outside UK?
I researched to see if other countries have something similar for Somatuline (Lanreotide) – please note not all patients will be eligible so you need to check first:
1. The Netherlands. I attended ENETS Barcelona and sat in on a presentation from a Nurse in The Netherlands who described a similar scheme. The presentation was entitled Home Injection Service for Somatostatin Analogues so may also include Octreotide. Contact is Wanda Geilvoet at the Erasmus Medical Centre in Rotterdam.
2. USA. Ipsen US appears to have a similar scheme through their Ipsen Cares program. It’s called “Home Health Administration (HHA)”. This is available for patients who are unable to receive their Somatuline Depot injections at the doctor’s office. Eligible patients can have a nurse visit their home to administer their injections. There is no cost to the patient for this option. HHA must be requested by the doctor and the patient must be enrolled in IPSEN CARES. The Nurse HHA Program is an additional offering of
IPSEN CARES available via a doctor for all eligible patients prescribed
• A physician must prescribe Somatuline Depot to be administered by Nurse
Home Health Administration for the patient.
• The program is available to most patients covered by commercial insurance
• Patients may not participate if prescriptions are eligible to be paid in part or
full by any state or federally funded programs, including, but not limited to
Medicare or Medicaid, VA, DOD, or TRICARE.
• Residents of Massachusetts, Michigan, Minnesota, and Rhode Island are not
3. Canada. There is not enough detail on the Ipsen Canada site to say there is a scheme but worth asking. Click here
4. Australia. There seems to be a programme called ‘Assist’. Click here for more details.
5. Republic of Ireland. They have the same service as UK, also called HomeZone. They will send a trained nurse out to your home monthly to do the injection for you free of charge. To arrange, the number is 01 4291820
I will add other locations as and when I find out.
Let’s share data!
I’m sure there must be more countries involved so please let me know. In fact, would UK patients let me know if you are on the ‘Homezone’ scheme where a nurse comes to your house and administers the drug, and via which hospital was this arranged. I’ll update the blog so we can all find out about it.
How’s it going so far?
On 26th November 2018, I had my 18th ‘HomeZone+ nurse administered injection and a permanent nurse allocated to my area. It’s a first class service from the main UK provider – Healthcare at Home (HAH) (I’m told Lloyds Pharmacy do certain areas). I’m told which day it will arrive and I receive two text messages with timings, the second one is a more precise time allowing me to get on with my life. The Nurse then makes an appointment to come and administer the injection. This works excellently too. The Nurse calls me with some notice in order to get the injection out of the fridge ready for administration. The injection is given very efficiently and my next appointment is made ready for 28 days time. I also found out that sharps box provision and collection is available through the programme, another bonus.
So far so good.
You may also appreciated my other blog posts on Somatostatin Analogues and Lanreotide (Somatuline):
Somatostatin Analogues are the ‘workhorse’ treatments for those living with NETs, particularly where certain syndromes are involved. So not just for classic NETs with Carcinoid Syndrome but also for treating insulinoma, gastrinoma, glucagonoma and VIPoma (all types of pNETs) and others. They are most effective if the NETs express somatostatin receptors. They also have an anti-tumour effect but more of a slowing down of growth rather than a killing or reduction of tumour size – but there are always outliers where such effects are displayed.
Somatostatin is actually a naturally occurring hormone produced by the hypothalamus and some other tissues such as the pancreas and the gastrointestinal tract. However, it can only handle the normal release of hormones. When NET syndromes occur, the naturally occurring somatostatin is unable to cope. The word ‘analogue’ in the simplest of terms, means ‘manufactured’ and a somatostatin analogue is made to be able to cope with the excess secretion (in most cases).
Although there is hidden complexity, the concept of the drug is fairly simple. It can inhibit insulin, glucagon, serotonin, VIP, it can slow down bowel motility and increase absorption of fluid from the gut. It also has an inhibitory effect on growth hormone release from the pituitary gland (thus why it’s also used to treat a condition called Acromegaly). You can see why it’s a good treatment for those with NET syndromes, i.e. who suffer from the excess secretions of hormones from their NETs. Clearly there can be side effects as it also inhibits digestive enzymes which can contribute to, or exacerbate, gastro-intestinal malabsorption.
Please note somatostatin analogues are not chemo. There are two major types in use:
Octreotide – or its brand name Sandostatin. It is suffixed by LAR for the ‘long acting release’ version.
Lanreotide – brand name Somatuline (suffixed by ‘Depot’ in North America, ‘Autogel’ elsewhere)
So what’s the difference between the two?
A frequently asked question. Here’s a quick summary:
They are made by two different companies. Novartis manufactures Octreotide and Ipsen manufactures Lanreotide. Octreotide has been around for much longer.
The long-acting versions are made and absorbed very differently. Octreotide has a complex polymer and must be injected in the muscle to absorb properly. Lanreotide instead uses has a novel nanotube structure and is water based (click here to see a video of how this works). It is injected deep-subcutaneously and is therefore easier to absorb and is not greatly impacted if accidentally injected into muscle.
Their delivery systems are mainly via injections but are fundamentally different as you can see from the blog graphic which shows the differences between the long acting release versions. Octreotide long acting requires a pre-mix, whilst Lanreotide comes pre-filled.
The long-acting versions are 60, 90 and 120 mg for Lanreotide and 10, 20 and 30 mg for Octreotide.
Octreotide also has a daily version which is administered subcutaneously.
Octreotide has something called a ‘rescue shot’ which is essentially a top up to tackle breakthrough symptoms. It is a subcutaneous injection.
You can also ‘pump’ Octreotide using a switched on/off continuous infusion subcutaneously.
Other than for lab/trial use, to the best of my knowledge, there is no daily injection, rescue shot or ‘pump’ for Lanreotide that is indicated for patient use.
Whilst both have anti-tumour effects, there are differences in US FDA approval: Octreotide (Sandostatin) is approved for symptom control (not anti-tumor) whereas Lanreotide (Somatuline) is approved for tumour control. However, the US FDA recently added a supplemental approval for syndrome control on the basis that it is proven to reduce the need for short acting somatostatin analogues use – read more here. This supplementary approval followed the ELECT trial – results here.
Always refer to the patient information leaflet as it is not safe to assume that all healthcare professionals are familiar with the administration. Common issues include (but are not limited to): drug temperature requirements, injection site, pinching vs stretching skin, speed of injection.
Please note a new syringe for Lanreotide will be available in June 2019. Further information will be communicated to healthcare professionals in advance of this, to enable them to inform their patients, whom have been prescribed Lanreotide. In addition, the patient information leaflet included in the packet will have clear instructions for use. There will be a prominent yellow box located on the outer carton of the medicine, alerting healthcare professionals and patients that a new syringe is contained inside. Please note that the medicine is still the same and the formulation and storage conditions have not changed.
Here are some interesting videos showing and explaining their administration:
Administering a Somatuline Depot (Lanreotide) injection:
Administering a Sandostatin LAR (Octreotide) injection:
This link also provides guidance on the “new formulation” Octreotide. Click here.
My own experience only includes daily injections of Octreotide (Sep-Nov 2010) and Lanreotide (Dec 2010 onwards). I’ve also had continuous infusion of Octreotide in preparation for surgical or invasive procedures over the period 2010-2012 (i.e. crisis prevention). You can read about my Lanreotide experience by clicking here. If you are interested in what might be coming downstream, please see my blog entitled ‘Somatostatin Analogues and Delivery Systems in the Pipeline’.
Injection site granulomas (lumps)
The issue of ‘granulomas‘ or ‘injection site granulomas’ seems to figure in both drugs. Gluteal injection site granulomas are a very common finding on CT and plain radiographs. They occur as a result of subcutaneous (i.e. intra-lipomatous) rather than intramuscular injection of drugs, which cause localised fat necrosis, scar formation and dystrophic calcification. But no-one seems to know why they occur with somatostatin analogues.
Personally, I find that they are more conspicuous if the injection is done slightly too high which was my initial experience and they took months to fade. I opted to stand up for the first two injections and I attribute this decision for a slightly too high injection site. I now lie down which is actually recommended for the smaller and thinner patient. Although the lumps have reduced in size, I have not seen a new lump for some time indicating location might have been the cause. They sometimes show up on scans. This is not a new problem and has been highlighted for the last 10 years in academic papers. This particular paper is useful and the conclusion confirms this is not something that should worry patients too much. Read more here
Somatostatin Analogues and raised blood sugar levels
It is well documented that both Octreotide and Lanreotide can elevate blood glucose (sugar) levels. Read more in my article Diabetes – the NET Effect.
Please note a new syringe for Lanreotide will be available in 2019, at least in Ireland and UK which have confirmed dates. However, Ipsen are committed to roll it out to the rest of Europe, US, Canada, Australia and New Zealand by end of 2019 (details to follow) following necessary regulatory approvals.
Further information will be communicated to healthcare professionals in advance of this, to enable them to inform their patients, whom have been prescribed Lanreotide. In addition, the patient information leaflet included in the packet will have clear instructions for use. There will be a prominent yellow box located on the outer carton of the medicine, alerting healthcare professionals and patients that a new syringe is contained inside.
The new pre-filled syringe for Somatuline® Autogel® was the result of several studies, involving patients, their caregivers, nurses and other healthcare professionals, to inform and test enhancements to the existing pre-filled syringe. Notable new features are modified ergonomics and handling, a needle shield removal system, an injection process with plunger support and heightened ease of use. The automatic, built-in safety system, which helps to prevent needle stick injury by locking in place following the administration, has not been changed.
Please note that the medicine is still the same and the formulation and storage conditions have not changed.
My Lanreotide Experience
When I was discharged from hospital following major surgery in Nov 2010, I knew I would shortly be commencing long-term monthly ‘somatostatin analogue’ treatment and had assumed Octreotide (Sandostatin LAR) would be the drug of choice. However, my Oncologist prescribed Lanreotide (known in the UK as Somatuline Autogel and elsewhere as Somatuline Depot). Technically this is a hormone therapy (it’s not chemo).
Somatostatin Analogues (Octreotide/Lanreotide) are mainstay treatments for many Neuroendocrine Cancer patients and their introduction is a very significant factor in the improvement of both prognostic outcomes and quality of life. Both drugs are designed to control Carcinoid Syndrome (but can be used selectively in other NET syndromes) and both have anti-tumour effects. Check out my Lanreotide vs Octreotide comparison blog.
Although I didn’t relish the thought of any injection in the ‘rear end’ every 28 days for the rest of my life, I admit to being slightly relieved with his choice. I had been reading about patient experiences with the alternative, mainly the needle length and the occasional problems mixing the drug prior to injection. Although Lanreotide has a similar gauge (thickness), the needle is a good bit shorter and is deep subcutaneous rather than Octreotide LAR’s intramuscular (IM) route. No mixing is required as Lanreotide comes prefilled.
If you’re interested in the science, please be aware that a somatostatin analogue is a synthetic (manufactured) version of a naturally occurring hormone which inhibits the peptides and amines that can be dangerously hypersecreted by certain neuroendocrine tumours.
Following an Octreotide Scan, various areas lit up confirming the output from previous CT scans. It also confirmed new ‘hotspots’ for further investigation. This specialist scan confirmed I probably had working receptors to receive something known as a Somatostatin Analogue to help with combatting the effects of Carcinoid Syndrome (please note that not having working receptors does not mean there is no benefit of receiving somatostatin analogues). I was therefore prescribed daily Octreotide (self-injecting) whilst I was waiting for my first major ‘debulking’ surgery, This treatment did eventually lessen the main effect of the carcinoid syndrome, facial flushing. It wasn’t until after my first surgery that the facial flushing was dramatically reduced. I commenced Lanreotide on 9 Dec 2010 and I haven’t had a facial flush since. It’s worth adding that my Chromogranin A (CgA) blood test (correlated to tumour mass) did not return to normal until after a liver resection 3 months later. My 5HIAA urine test results (mainly correlated to serotonin levels) returned to normal prior to liver surgery in Apr 2011 indicating the Lanreotide was doing its job! Somatostatin Analogue side effects are to be expected and most people seem to have different and/or greater or lesser effects than others. The daily Octreotide did not bother me too much other than some discolouring of the stomach at the injection sites (i.e. black and blue!) ….I’m more observant nowadays, so it’s possible I may not have recorded this experience properly.
If you read the UK patient leafletwhich comes with each injection, you can see a list of potential side effects as long as your arm. Neuroendocrine Cancer comes with many signs, syndromes, symptoms and suspicions, so I always advise caution and some analysis when assigning reasons for problems encountered. For North America, the equivalent instructions can be found here (Somatuline Depot). I don’t know precisely why (……. I do have my suspicions), but I’m always very sceptical about the criteria used to compile the list of side effects for any medicine. In my own mind, I’m fairly certain that people have existing symptoms or new symptoms as a result of coincidental treatment that are erroneously labelled under drugs during trials.
You can also self-inject Lanreotide but I’m not ready for that yet! If you do self inject, please note it the site is “the upper outer part of your thigh”. Check out the Ipsen leaflet here.
I think the injection site is very important and getting this wrong will worsen the side effects. For the Healthcare Professional or trained family member administration, the site should be the superior external quadrant but not of the whole ‘butt’, it means of the left or right buttock that is being used on an alternative basis. If nurses think the whole ‘butt’, they might be tempted to stick it quite close to the ‘intergluteal cleft’ – not advisable!
Although the patient leaflets are very clear on how to administer the drug, once the location is established, I always discuss the following with the Nurse before I receive the ‘dart’:
1. The injection should have been removed from the fridge at least 30 minutes before treatment. However, please note Ipsen clarified in 2019 that the product can be put back in the fridge in the original packaging for later use, provided it has been stored for no longer than 24 hours at below 40 deg C (104 deg F) and the number of ‘temperature excursions’ does not exceed three. If you are taking the drug somewhere to be administered or were waiting on a home visit, this might help with scheduling issues.
2. Don’t pinch the skin, stretch it.
3. Put the needle in fast at 90 degrees, inject the drug slow – 20 seconds is recommended. As the drug is viscous, in any case, there is normally some resistance to a fast release.
4. Do not rub or massage the area after as this action can interfere with the formulation of the drug. This is clearly stated on the drug information leaflet, i.e. ” Apply gentle pressure to the injection site with a dry cotton ball or sterile gauze to prevent any bleeding. Do not rub or massage the injection site after administration”.
My experience with side effects. People have different experiences with side effects and just because a particular side effect is mentioned, does not mean to say that everyone will be troubled – many patients experience little or none. For me, over 7 years, I think I can attribute the following to Lanreotide:
itching but only on the legs below the knees centred on the ankles – and nearly always the right leg. Occasionally, the injection site will itch but only for a day or two. I have a tub of emollient cream (almond oil) on standby which seems to calm it down. Note …… a little bit of me thinks there could be a connection with vitamin/mineral deficiency and perhaps a coincidental occurrence and this problem seems much less of an issue over 7 years later. EDIT- could have been Hypothyroidism – click here.
minor pain at the injection site but this only lasts for an hour or two and I believe this to be associated with the administration of the injection, i.e. if the injection is done properly, I don’t really have this problem except for a second or two as it enters. Once, I had pain for 10 days. In my own experience, the best and least painful injections are those done by trained personnel who are confident.
small lumps form at the injection site which is alternating superior external quadrant of the each buttock. You may occasionally hear these being called ‘granulomas‘ or ‘injection site granulomas’. The issue of ‘injection site granulomas’ seems to figure in both Lanreotide and Octreotide. Gluteal injection site granulomas are a very common finding on CT and plain radiographs. They occur as a result of subcutaneous (i.e. intra-lipomatous) rather than intramuscular injection of drugs, which cause localised fat necrosis, scar formation and dystrophic calcification. But no-one seems to know why they occur with somatostatin analogues. I find that they are more conspicuous if the injection is done slightly too high which was my initial experience and they took months to fade. I opted to stand up for the first two injections and I attribute this decision for a slightly too high injection site. I now lie down which is actually recommended for the smaller and thinner patient. Although the lumps have reduced in size, I have not seen a new lump for some time indicating location might have been the cause. They sometimes show up on scans. This is not a new problem and has been highlighted for the last 10 years in academic papers. This particular paper is useful and the conclusion confirms this is not something that should worry patients too much. Read more here
fatigue normally within 24-48 hours of the injection but this is not consistent. Not even sure it can be classed as proper fatigue but it’s a ‘you need to sit down and fall asleep‘ feeling! When this occurs, it normally only lasts for 1 day before the normal energy levels return. Again, like the itching, this appears to be less of an issue today.
malabsorption. although the side effects of gastro-intestinal (GI) surgery and gallbladder removal can cause malabsorption issues leading to steatorrhea (basically the inability to digest fat properly); somatostatin analogues can cause or exacerbate existing steatorrhea, as they inhibit the production of digestive/pancreatic enzymes which aid fat digestion. Most months, I notice a marked but short-term increase in this problem normally within 48-72 hours of the injection.
elevated blood glucose. This is a new issue in 2018 but has been brewing for a year or two. The patient information leaflet for Lanreotide (and for Octreotide) clearly states that this is a potential side effect and also asks those who are already diabetic, to consult their doctor about monitoring doses of diabetic medicine. I’m working with my doctors to keep my blood glucose down to avoid becoming diabetic. Please read this article covering the connections between NETs and Diabetes
A few years ago, there was some ‘talk’ that somatostatin analogues were also able to stunt or reverse the growth of certain neuroendocrine tumours. Has this been the case for me? Possibly. I’ve had regular CT scans every 3-6 months and since two bouts of major surgery in 2010/2011, I’ve also had 3 x Octreoscans over the same period. I did once spend a day analysing 5 years of scan results looking for variations in size and concluded that there was a stable trend and potentially a fading of one or two of my largest liver tumours. I was reminded these two types of scans were not really precise enough to detect small millimetre increases or decreases and as there were other factors at play, there was little commitment to make this declaration. However, I did note in the summary of theCLARINETstudy, Lanreotide was associated with prolonged progression-free survival among patients with advanced, grade 1 or 2 (Ki-67 <10%) enteropancreatic, somatostatin receptor–positive neuroendocrine tumours with prior stable disease, irrespective of the hepatic tumour volume. In terms of its anti-proliferative effects, aninterim report from the CLARINET extension studysuggested longer-term Lanreotide treatment is well tolerated with ‘anti-tumour’ effects in patients with progressive disease. The final CLARINET open label extension studyreport additionally provided evidence for long-term PFS benefits of Lanreotide Autogel 120 mg in patients with indolent pancreatic and intestinal NETs.
There’s currently a trial ongoing in relation to Lanreotide and Lung NETs – read by clicking here.
I have my ups and downs and I do feel quite well most of the time. Most people tell me I look quite well too – lucky they can’t see my insides! Over the last 7 years, I’ve made some fairly significant adjustments to cope with my condition and maintain a reasonable quality of life – my monthly injection of Lanreotide is no doubt playing a big part.
Finally, please spend 5 minutes watching this fascinating video from Ipsen. It explains in easy terms how Lanreotide works. It also has a useful summary of the side effects at the end. Click here to watch the video.
I’ve just been enrolled onto a new service called HomeZone whereby the injection is now administered at my home via an Ipsen provided and funded nurse. Read here to see if you can also take advantage of this service.
In July 2018, I received my 100th injection of Somatuline Autogel (Lanreotide). I was very grateful to still be here so I thought it was worth a celebratory cake – injection themed!