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13-09-2016 | Neuroendocrine tumors | Article

Lanreotide Depot: An Antineoplastic Treatment of Carcinoid or Neuroendocrine Tumors

Journal: Journal of Gastrointestinal Cancer

Authors: Edward M. Wolin, Amandine Manon, Christophe Chassaing, Andy Lewis, Laurent Bertocchi, Joel Richard, Alexandria T. Phan

Publisher: Springer US

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Abstract

Purpose

Peptide drugs for antineoplastic therapies usually have low oral bioavailability and short in vivo half-lives, requiring less preferred delivery methods. Lanreotide depot is a sustained-release somatostatin analog (SSA) formulation produced via an innovative peptide self-assembly method. Lanreotide is approved in the USA and Europe to improve progression-free survival (PFS) in patients with unresectable gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and also approved in Europe for symptom control in carcinoid syndrome associated with GEP-NETs. This review discusses how the distinct molecule and formulation of lanreotide depot provide advantages to patients and health care providers, as well as the most recent clinical evidence demonstrating the safety and efficacy of lanreotide depot in inhibiting tumor growth and controlling hormonal symptoms in GEP-NETs.

Methodology and Results

The lanreotide depot formulation confers a remarkable pharmacokinetic profile with no excipients, comprised only of lanreotide acetate and water. Of note, lanreotide depot constitutes an example for peptide self-assembly based formulations, providing insights that could help future development of sustained-release formulations of other antineoplastic peptides. Most patients with GEP-NETs will present with inoperable or incurable disease; thus, medical management for symptoms and tumor control plays a crucial role. Recent long-term clinical studies have demonstrated that lanreotide depot is well tolerated, prolongs PFS in GEP-NET patients, and significantly reduces symptoms related to carcinoid syndrome.

Conclusions

The unique depot formulation and delivery method of lanreotide confer advantages in the treatment of metastatic GEP-NETs, contributing to improvements in NET-related symptoms and PFS without reducing quality of life in this patient population.
Literature
1.
Thundimadathil J. Cancer treatment using peptides: current therapies and future prospects. J Amino Acids. 2012;2012:967347.CrossRefPubMedPubMedCentral
2.
Maji SK, Schubert D, Rivier C, et al. Amyloid as a depot for the formulation of long-acting drugs. PLoS Biol. 2008;6:e17.CrossRefPubMedPubMedCentral
3.
Lewis AL, Illum L. Formulation strategies for sustained release of proteins. Ther Deliv. 2010;1:457–79.CrossRefPubMed
4.
Dobson CM. The structural basis of protein folding and its links with human disease. Philos Trans R Soc Lond Ser B Biol Sci. 2001;356:133–45.CrossRef
5.
Somatuline Autogel [SPC]. Somatuline Autogel, solution for injection in a prefilled syringe [summary of product characteristics]. Paris: Ipsen Ltd; 2013.
6.
Somatuline Depot [package insert]. Basking Ridge, NJ: Ipsen Biopharmaceuticals, Inc; 2014.
7.
Cives M, Strosberg J. An update on gastroenteropancreatic neuroendocrine tumors. Oncology (Williston Park). 2014;28:201359.
8.
Fraenkel M, Kim M, Faggiano A, et al. Incidence of gastroenteropancreatic neuroendocrine tumours: a systematic review of the literature. Endocr Relat Cancer. 2014;21:R153–63.CrossRefPubMed
9.
Lawrence B, Gustafsson BI, Chan A, et al. The epidemiology of gastroenteropancreatic neuroendocrine tumors. Endocrinol Metab Clin N Am. 2011;40:1–18 .viiCrossRef
10.
Lawrence B, Gustafsson BI, Kidd M, et al. The clinical relevance of chromogranin A as a biomarker for gastroenteropancreatic neuroendocrine tumors. Endocrinol Metab Clin N Am. 2011;40:111–34 .viiiCrossRef
11.
Oberg KE. The management of neuroendocrine tumours: current and future medical therapy options. Clin Oncol (R Coll Radiol). 2012;24:282–93.CrossRef
12.
Caplin ME, Pavel M, Cwikla JB, et al. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med. 2014;371:224–33.CrossRefPubMed
13.
Wolin EM. The expanding role of somatostatin analogs in the management of neuroendocrine tumors. Gastrointest Cancer Res. 2012;5:161–8.PubMedPubMedCentral
14.
Modlin IM, Moss SF, Gustafsson BI, et al. The archaic distinction between functioning and nonfunctioning neuroendocrine neoplasms is no longer clinically relevant. Langenbeck's Arch Surg. 2011;396:1145–56.CrossRef
15.
Rinke A, Muller HH, Schade-Brittinger C, et al. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID study group. J Clin Oncol. 2009;27:4656–63.CrossRefPubMed
16.
Plourde F, Motulsky A, Couffin-Hoarau AC, et al. First report on the efficacy of l-alanine-based in situ-forming implants for the long-term parenteral delivery of drugs. J Control Release. 2005;108:433–41.CrossRefPubMed
17.
Siepmann J, Faisant N, Akiki J, et al. Effect of the size of biodegradable microparticles on drug release: experiment and theory. J Control Release. 2004;96:123–34.CrossRefPubMed
18.
Estey T, Kang J, Schwendeman SP, et al. BSA degradation under acidic conditions: a model for protein instability during release from PLGA delivery systems. J Pharm Sci. 2006;95:1626–39.CrossRefPubMed
19.
Gobeaux F, Fay N, Tarabout C, et al. Structural role of counterions adsorbed on self-assembled peptide nanotubes. J Am Chem Soc. 2012;134:723–33.CrossRefPubMed
20.
Gobeaux F, Fay N, Tarabout C, et al. Experimental observation of double-walled peptide nanotubes and monodispersity modeling of the number of walls. Langmuir. 2013;29:2739–45.CrossRefPubMed
21.
Pandit A, Fay N, Bordes L, et al. Self-assembly of the octapeptide lanreotide and lanreotide-based derivatives: the role of the aromatic residues. J Pept Sci. 2008;14:66–75.CrossRefPubMed
22.
Pouget E, Dujardin E, Cavalier A, et al. Hierarchical architectures by synergy between dynamical template self-assembly and biomineralization. Nat Mater. 2007;6:434–9.CrossRefPubMed
23.
Pouget E, Fay N, Dujardin E, et al. Elucidation of the self-assembly pathway of lanreotide octapeptide into beta-sheet nanotubes: role of two stable intermediates. J Am Chem Soc. 2010;132:4230–41.CrossRefPubMed
24.
Tarabout C, Roux S, Gobeaux F, et al. Control of peptide nanotube diameter by chemical modifications of an aromatic residue involved in a single close contact. Proc Natl Acad Sci U S A. 2011;108:7679–84.CrossRefPubMedPubMedCentral
25.
Valery C, Paternostre M, Robert B, et al. Biomimetic organization: octapeptide self-assembly into nanotubes of viral capsid-like dimension. Proc Natl Acad Sci U S A. 2003;100:10258–62.CrossRefPubMedPubMedCentral
26.
Valery C, Artzner F, Robert B, et al. Self-association process of a peptide in solution: from beta-sheet filaments to large embedded nanotubes. Biophys J. 2004;86:2484–501.CrossRefPubMedPubMedCentral
27.
Valery C, Pouget E, Pandit A, et al. Molecular origin of the self-assembly of lanreotide into nanotubes: a mutational approach. Biophys J. 2008;94:1782–95.CrossRefPubMedPubMedCentral
28.
Cherif-Cheikh R, Bismuth F, Torres M, et al. Autogel: a new lanreotide prolonged release formulation. Proceed Int'l Symp Control Rel Bioact Mater. 1998;25:798.
29.
Troconiz IF, Cendros JM, Peraire C, et al. Population pharmacokinetic analysis of lanreotide Autogel in healthy subjects: evidence for injection interval of up to 2 months. Clin Pharmacokinet. 2009;48:51–62.CrossRefPubMed
30.
Bronstein M, Musolino N, Jallad R, et al. Pharmacokinetic profile of lanreotide Autogel in patients with acromegaly after four deep subcutaneous injections of 60, 90 or 120 mg every 28 days. Clin Endocrinol. 2005;63:514–9.CrossRef
31.
Antonijoan RM, Barbanoj MJ, Cordero JA, et al. Pharmacokinetics of a new Autogel formulation of the somatostatin analogue lanreotide after a single subcutaneous dose in healthy volunteers. J Pharm Pharmacol. 2004;56:471–6.CrossRefPubMed
32.
Adelman DT, Burgess A, Davies PR. Evaluation of long-acting somatostatin analog injection devices by nurses: a quantitative study. Med Devices (Auckl). 2012;5:103–9.CrossRef
33.
Marty R, Roze S, Kurth H. Decision-tree model for health economic comparison of two long-acting somatostatin receptor ligand devices in France, Germany, and the UK. Med Devices (Auckl). 2012;5:39–44.
34.
Boyd AE, DeFord LL, Mares JE, et al. Improving the success rate of gluteal intramuscular injections. Pancreas. 2013;42:878–82.CrossRefPubMed
35.
Palma S, Strohfus P. Are IM injections IM in obese and overweight females? A study in injection technique. Appl Nurs Res. 2013;26:e1–4.CrossRefPubMed
36.
Alexopoulou O, Abrams P, Verhelst J, et al. Efficacy and tolerability of lanreotide Autogel therapy in acromegalic patients previously treated with octreotide LAR. Eur J Endocrinol. 2004;151:317–24.CrossRefPubMed
37.
Sandostatin LAR [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2014.
38.
Kulke MH, Siu LL, Tepper JE, et al. Future directions in the treatment of neuroendocrine tumors: consensus report of the National Cancer Institute Neuroendocrine Tumor clinical trials planning meeting. J Clin Oncol. 2011;29:934–43.CrossRefPubMedPubMedCentral
39.
Khan MS, El-Khouly F, Davies P, et al. Long-term results of treatment of malignant carcinoid syndrome with prolonged release lanreotide (Somatuline Autogel). Aliment Pharmacol Ther. 2011;34:235–42.CrossRefPubMed
40.
Caplin ME, Pavel M, Ćwikła JB, et al. Anti-tumour effects of lanreotide for pancreatic and intestinal neuroendocrine tumours: the CLARINET open-label extension study. Endocr Relat Cancer. 2016;23:191–9.CrossRefPubMedPubMedCentral
41.
Bajetta E, Procopio G, Catena L, et al. Lanreotide autogel every 6 weeks compared with lanreotide microparticles every 3 weeks in patients with well differentiated neuroendocrine tumors: a phase III study. Cancer. 2006;107:2474–81.CrossRefPubMed
42.
Martin-Richard M, Massuti B, Pineda E, et al. Antiproliferative effects of lanreotide autogel in patients with progressive, well-differentiated neuroendocrine tumours: a Spanish, multicentre, open-label, single arm phase II study. BMC Cancer. 2013;13:427. doi:10.​1186/​1471-2407-13-427.CrossRefPubMedPubMedCentral
43.
Vinik AI, Wolin EM, Liyanage N, et al. Evaluation of lanreotide depot/autogel efficacy and safety as a carcinoid syndrom treatment (ELECT): a randomized, double-blind, placebo-controlled trial. Endocr Pract. 2016 May 23. doi:10.​4158/​EP151172.​OR.
44.
Ruszniewski P, Valle JW, Lombard-Bohas C, et al. Patient-reported outcomes with lanreotide autogel/depot for carcinoid syndrome: an international observational study. Dig Liver Dis. 2016;48(5):552–8.