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 the hormone overscretions caused by 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 chemotherapy. 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 into 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. Octreotide long-acting requires a pre-mix, whilst Lanreotide comes pre-filled. Please note that Ipsen is rolling out a new Lanreotide delivery system. You can read a review entitled “An International Simulated Use Study (PRESTO) to Evaluate Nurse Preferences Between the Lanreotide Autogel New Syringe and Octreotide Long-Acting Release Syringe” – click here.
- 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 (or rescue shot) which is administered subcutaneously. Dosages range from 100-500 micrograms. A rescue shot is essentially a top-up to tackle breakthrough symptoms as quickly as possible (I have heard of some Lanreotide users also taking Octreotide rescue shots).
- 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 via studies (see below), 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 added a supplemental approval for Lanreotide 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. Read more about Lanreotide clinical trials here. The study confirming the anti-tumour benefits of Octreotide can be found here.
- Octreotide has had many variants or ‘generics’ deployed over the years, Lanreotide variants only turned up in late 2021. Read more here.
- Technical Article comparing both – click here or the picture below.
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.
Here are some interesting videos showing and explaining their administration:
Administering a Somatuline Depot (Lanreotide) injection:
Click here or the picture below. This is the US version but the administration is the same anywhere.
Please note this is a US video thus the name Somatuline Depot rather than Autogel. Plus, some of the rules regarding who and where the injection can take place may not apply to your country. Also, any mention of approval wording may differ.
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 pain
I don’t really get much pain with Lanreotide and on a 10-point pain scale, I don’t think I would even score at 1. I believe there are a few factors for a successful injection in addition to the ones listed on the drug insert leaflets. The experience and confidence of the person administering the injection (which includes adherence to the drug insert leaflet). Secondly, a nervous patient who is unable to relax is most likely going to add to a degraded experience.
However, I see many comments in my online patient support group, some report severe pain and some need cooling or pain reducing aids prior to the injection. I think it is mostly tolerated though and the study below seems to confirm this.
Nitya Raj, MD, clinical director, Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, discusses the results of a phase 4 trial (NCT03289741) comparing injection site pain with octreotide long-acting release (LAR) vs lanreotide in well-differentiated neuroendocrine tumors (NETs).
The results of this randomized, blinded trial, which were presented during the 2021 NANETS Symposium, did not demonstrate a significant difference in the patient experience regarding comfort and pain with the injection with octreotide LAR vs lanreotide, Raj says. Among patients who received octreotide LAR first, the mean injection site pain score was 2.4 compared with 1.9 in patients who received lanreotide first, Raj explains.
The difference in these pain scores was not statistically significant, Raj continues. Moreover, it is important to recognize that out of a 10-point scale, the pain experienced by patients was relatively low overall, Raj concludes. See video from Dr Raj here.
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.
Somatostatin Analogues and thyroid levels
It is well documented that both Octreotide and Lanreotide can mess with thyroid hormone levels. Read more in my article on Don’t be underactive with your Thyroid surveillance.
Somatostatin Analogues and pancreatic enzyme levels
It is known that somatostatin analogues can inhibit levels of pancreatic enzymes in some and in varying degrees. Read more in my article Neuroendocrine Cancer and Pancreatic Enzyme Replacement Therapy (PERT) – the Digested Version (Nutrition Series Article 5) – Ronny Allan – Living with Neuroendocrine Cancer
People ask about other/future delivery methods, e.g. capsules etc, but nothing is yet approved for NET. There are several initiatives in the pipeline, and you can find details of these by clicking on the picture above.
I am not a doctor or any form of medical professional, practitioner or counsellor. None of the information on my website, or linked to my website(s), or conveyed by me on any social media or presentation, should be interpreted as medical advice given or advised by me.
Neither should any post or comment made by a follower or member of my private group be assumed to be medical advice, even if that person is a healthcare professional.
Please also note that mention of a clinical service, trial/study or therapy does not constitute an endorsement of that service, trial/study or therapy by Ronny Allan, the information is provided for education and awareness purposes and/or related to Ronny Allan’s own patient experience. This element of the disclaimer includes any complementary medicine, non-prescription over the counter drugs and supplements such as vitamins and minerals.
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