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varies from 0.1 mg to 0.3 mg subcutaneously two to three symptoms in patients with carcinoid tumors, gastrinomas,
times daily, but doses up to 3 mg/day may be necessary for and vasoactive intestinal peptide tumors (VIPomas). [40-42]
symptom control. The LAR formulation of octreotide is A new slow-release depot preparation of lanreotide,
commonly used for the chronic management of symptoms “Lanreotide Autogel” administered subcutaneously at a
in patients with carcinoid syndrome. Standard doses are dose of 60, 90, or 120 mg once a month was thereafter
20 mg to 30 mg, intramusculary, every 4 weeks. Dose and produced. The international phase III ELECT trial
frequency may be further increased for symptom control randomized 115 patients with carcinoid syndrome who
as needed. Therapeutic levels are not achieved for 10 were either naive to or responsive to octreotide to receive
to 14 days after LAR injection. Short-acting octreotide 120 mg of lanreotide or placebo. Although the pre-
[43]
(usually 150-250 mcg subcutaneously 3 times daily) can defined difference in percentage of days the patients used
be added to octreotide LAR for rapid relief of symptoms rescue octreotide was not met, the panel believes that
or for breakthrough symptoms. [35,36] A randomized study the difference seen (34% in the lanreotide arm vs. 49%
comparing daily injection with octreotide to octreotide LAR in the placebo arm; P = 0.02) was significant enough
every 4 weeks in the symptomatic treatment of 93 patients to warrant use of lanreotide for symptom control. The
noted at least as good symptomatic efficacy for depot recommendation that lanreotide be considered for control
octreotide at various dosages (10, 20, 30 mg) compared of tumor growth in patients with clinically significant
to subcutaneously octreotide. The recommendation to tumor burden or progressive disease is based on results of
[37]
consider octreotide in patients with large tumor burden or the CLARINET study. The CLARINET study randomized
progressive disease is based on the results of the PROMID 204 patients with locally advanced or metastatic non-
study, a placebo-controlled phase III trial of 85 patients with functioning pancreatic or intestinal neuroendocrine tumors
metastatic midgut neuroendocrine tumors. This showed to receive either lanreotide or placebo and followed
median time to tumor progression of 14.3 and 6 months in patients for progression-free survival (PFS). Results
the octreotide LAR and placebo groups, respectively (P = showed that treatment with lanreotide for 2 years resulted
0.000072). After 6 months of treatment, stable disease in an improvement in PFS over placebo (PFS not reached
[34]
was observed in 66.7% of patients in the octreotide LAR vs. 18 months; HR 0.47; 95% CI 0.30-0.73; P < 0.001). [44]
group and in 37.2% of patients in the placebo group.
Results of long-term survival of patients in the PROMID No clear consensus exists on the timing of octreotide
study were recently reported. Median overall survival or lanreotide initiation in asymptomatic patients with
[38]
(OS) for was not significantly different at 84 months in metastatic neuroendocrine tumors and low tumor
the placebo arm and not reached in the octreotide arm burden. Although initiation of octreotide or lanreotide
[heart rate (HR) 0.85; 95% confidence interval (CI) 0.46- can be considered in these patients, deferring initiation
1.56; P = 0.59]. However, post-study treatment included until evidence of tumor progression is seen may also be
octreotide in 38 of 43 patients in the placebo arm, possibily appropriate in selected patients (National Comprehensive
confounding interpretation of long-term survival results. Cancer Network Guideline 2015).
Currently, the maximum Food and Drug Administration-
approved dosage and administration of octreotide long- PASIREOTIDE
acting repeatable (LAR), indicated for severe diarrhea/
flushing episodes associated with metastatic carcinoid Pasireotide (SOM 230) has high affinity for SSTR1, 2, 3, and
tumors and VIPomas, is 30 mg every 4 weeks. A 5, and displays a 30- to 40-fold higher affinity for SSTR1
[39]
recent physician expert consensus panel highlighted the and SSTR5 than octreotide or lanreotide. Octreotide and
[45]
appropriateness of using standard dose SSAs for control Lanreotide have been used to treat acromegaly successfully
of hormonal symptoms and tumor growth in patients with because 90% of GH-secreting pituitary tumours express
advanced carcinoid tumors, as well as increasing dose/ SSTR2 and SSTR5. However, given that pasireotide has
frequency of SSAs in treatment of refractory carcinoid 40-fold higher affinity and a 158-fold higher functional
syndrome. The panel also recommended that increase activity for SSTR5 than octreotide, pasireotide may be
[33]
in the dose/frequency of SSAs be considered for patients more effective than octreotide in acromegaly. In phase II
[46]
with radiographic progression, particularly in cases where clinical trials, pasireotide has been demonstrated to inhibit
disease was previously stabilized at a lower dose. GH secretion from pituitary tumours, control symptoms of
the carcinoid syndrome associated with metastatic NETs,
LANREOTIDE and inhibit ACTH secretion in Cushing’s Disease. [47]

Lanreotide (BIM 23014) has a similar mechanism of CHEMOTHERAPY
action as octreotide, also displaying high-affinity binding
for types 2 and 5 receptors, low affinity for types 1 and 4, NENs usually arise as advanced and of low/intermediate
[48]
and medium affinity for type 3. Lanreotide is a long- grade and only in a minority of cases as high grade.
[17]
acting SSA analog administred every 10-14 days and Prognosis depends on the histological differentiation,
has a similar efficacy to octreotide in the treatment of staging, and grade. [49-51] Most are non-functioning and
NETs. Studies have shown it to be effective at controlling metastatic at diagnosis. Gastro-entero-pancreatic NENs
[52]
Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ August 31, 2016 ¦ 315