Lanreotide

Lanreotide is pharmacologically close to octreotide, with the same SSTR2-dominant, SSTR5-secondary binding profile and the same Gi-coupled suppression of hormone exocytosis. What differs is the formulation: the autogel is a supersaturated peptide-water gel with no polymer excipient, which forms a depot in subcutaneous tissue and releases drug over about a month. The CLARINET trial established a genuine antiproliferative effect, with markedly longer progression-free survival in enteropancreatic neuroendocrine tumours, so it is used as tumour therapy and not only as symptom control.

Targets: SSTR2, SSTR5, Growth hormone secretion, Neuroendocrine tumour proliferation

• · Start 90 mg every 4 weeks for three months, then adjust to 60, 90 or 120 mg on IGF-1. Well-controlled patients are sometimes extended to every 6 or 8 weeks.
• · 120 mg every 4 weeks is the licensed antitumour dose, continued until progression.

Work out your exact syringe units →

• very commonDiarrhoea and abdominal pain— Most prominent after the first few doses.
• commonCholelithiasis— Same bile-stasis mechanism as octreotide.
• commonInjection-site nodules and pain— The gel depot can be palpable for weeks.
• commonHyperglycaemia— Less pronounced than with pasireotide.
• uncommonSinus bradycardia— Check pulse in patients on beta-blockers.

• Hypersensitivity to lanreotide
• Caution with symptomatic gallstone disease
• Caution in diabetes, where oral agent and insulin doses often need adjusting

• redundantoctreotide — Same receptor targets; patients switch between them rather than combining.
• synergypegvisomant — Adding pegvisomant to a somatostatin analogue normalises IGF-1 in most partial responders.

• · IGF-1 before each dose adjustment
• · Gallbladder ultrasound periodically
• · Fasting glucose and HbA1c
• · Heart rate at clinic visits

Prescription drug in the US and EU; generics of the depot have started to appear.

• Somatuline Depot FDA prescribing information (label)
• Caplin et al. 2014 NEJM, CLARINET trial of lanreotide in enteropancreatic neuroendocrine tumours (trial)

Receptor pharmacology is close enough to octreotide that the interesting differences are formulation and tissue kinetics rather than signalling. Lanreotide is SSTR2-dominant with secondary SSTR5 binding, Gi-coupled, producing the same cyclic AMP fall, potassium efflux and calcium channel closure. What differs is that the autogel forms a solid-phase depot out of the peptide itself. There is no PLGA microsphere polymer to hydrolyse, so release is governed by the gel-water interface rather than polymer erosion, which is why the profile is smoother and why the depot can sit in subcutaneous fat instead of needing deep muscle. The apparent terminal half-life of 23 to 30 days is a flip-flop phenomenon: it reflects how fast the depot dissolves, not how fast the molecule is cleared. Practically that means you cannot rescue an overshoot by stopping, and dose changes need three or four cycles before the new steady state is readable. CLARINET's progression-free survival benefit was large and held in patients with low proliferative index and in non-functioning tumours, which is the strongest evidence in the class that the antiproliferative effect is real rather than an artefact of symptom control.

Injection technique is the usual failure. The syringe must come out of the fridge about 30 minutes before use, because cold gel is close to unpushable and forcing it slowly produces a painful superficial nodule. It goes deep subcutaneous into the upper outer buttock with the skin stretched flat rather than pinched, in one continuous push over roughly 20 seconds. Placed too shallow, the depot is palpable for weeks and releases erratically. The second trap is impatience: with an apparent half-life measured in weeks, an IGF-1 checked after one or two injections tells you nothing and titrating on it leads to overshooting. The third is assuming a normal IGF-1 means the tumour is stable, when it does not, and imaging still happens on schedule.

1. 90 mgMonths 1-3 — 90 mg deep subcutaneously every 4 weeks is the standard acromegaly starting dose.
2. 120 mgMonth 4 onward if IGF-1 is still high — Escalate to 120 mg every 4 weeks. This is also the fixed, non-titrated dose for gastroenteropancreatic neuroendocrine tumours.
3. 60 mgMonth 4 onward if IGF-1 is fully suppressed — Step down to 60 mg every 4 weeks, or keep 90 mg and extend the interval to 6 or 8 weeks, which many patients prefer.

• SSTR2 — Sub-nanomolar and primary. Numeric IC50 not resolved this session.

  Suppresses GH secretion from somatotroph adenomas and hormone release from gastroenteropancreatic neuroendocrine tumours; carries the SHP-1 antiproliferative signal.

• SSTR5 — Moderate

  Secondary contribution to GH suppression and to insulin suppression.

• SSTR1, SSTR3 and SSTR4 — Low to negligible

  Little clinical contribution.

• CLARINET Phase 3, randomised, double-blind, placebo-controlled · 2014

  Progression-free survival in metastatic enteropancreatic neuroendocrine tumours. Lanreotide 120 mg every 4 weeks produced a large and statistically robust prolongation of progression-free survival versus placebo, including in non-functioning tumours.

Serum lanreotide peaks within about a day. Symptom control in functioning tumours is often apparent within the first cycle. Hormonal control builds over the first one to two injections and steady state needs four or five, roughly four months. Any efficacy judgement before three injections is guesswork.

Same logic as octreotide: pegvisomant is the evidence-backed partner in acromegaly, cabergoline is the cheap adjunct worth trying first in mild residual disease, and stacking another somatostatin analogue is pointless. In neuroendocrine tumours lanreotide is increasingly the backbone that everything else is added to, including peptide receptor radionuclide therapy with lutetium-177 dotatate and, on progression, everolimus. The practical interaction to plan for is with oral diabetes agents and insulin, where doses often need trimming in the first month.

Versus octreotide LAR the receptor pharmacology is a wash and the difference is delivery: a ready-to-use deep subcutaneous prefilled syringe versus an intramuscular microsphere suspension that must be mixed and injected within minutes. That single fact drives most real-world prescribing. On the antiproliferative side CLARINET enrolled a broader and better-defined population than PROMID and is the stronger dataset, though nobody seriously argues the two drugs differ in tumour effect. Versus pasireotide, the same trade-off as octreotide: less efficacy in refractory acromegaly, dramatically less hyperglycaemia.

$5000–$12000/month. Unverified estimate of US list pricing for a single 120 mg autogel syringe, which is one month of therapy. Generic and biosimilar depot lanreotide has started to appear and is bringing that down. Not sourced in this session.

• ?Volume of distribution and plasma protein binding are not stated in the accessible sections of the Somatuline Depot label, so both are null.
• ?The 112-day time to steady state is inferred from the label statement that steady state follows 4 to 5 injections in GEP-NET patients; it is an inference from injection count, not a quoted number.
• ?CLARINET enrolled roughly 200 patients over 96 weeks, but I did not confirm either figure, so both are null.
• ?Cost figures are unverified estimates.

• Lanreotide in metastatic enteropancreatic neuroendocrine tumors Caplin ME, et al., New England Journal of Medicine, 2014 · PMID 25014687

  The CLARINET trial, and the strongest antiproliferative evidence for any somatostatin analogue.

• SOMATULINE DEPOT (lanreotide) injection - FDA prescribing information Ipsen Biopharmaceuticals, DailyMed

  Source of the 69 to 78 percent absolute bioavailability figures, the 23 to 30 day half-life, biliary elimination and the chemical name.