Predictive factors of antiproliferative activity of octreotide LAR as first-line therapy for advanced neuroendocrine tumours

Laskaratos, Faidon-Marios; Walker, Martin; Naik, Keval; Maragkoudakis, Emmanouil; Oikonomopoulos, Nikolaos; Grant, Lee Alexander; Meyer, Tim; Caplin, Martyn; Toumpanakis, Christos

doi:10.1038/bjc.2016.349

Cited by 26 publications

(28 citation statements)

References 22 publications

(40 reference statements)

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“…In men, asymptomatic patients with stable disease and carcinoid heart disease were favorable predictors of tumor response to SSAs. In this study, age, functional status of the tumor, primary tumor resection, extrahepatic metastases, and mesenteric desmoplasia did not seem to have any effect on treatment with SSAs [114].…”

Section: Antiproliferative Effects In Gep-netscontrasting

confidence: 48%

Somatostatin Analogs in Clinical Practice: A Review

Gomes-Porras

Cárdenas-Salas

Álvarez-Escolá

2020

IJMS

158

136

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Somatostatin analogs are an invaluable therapeutic option in the diagnosis and treatment of somatotropinomas, thyrotropinomas, and functioning and non-functioning gastroenteropancreatic neuroendocrine tumors. They should also be considered an effective and safe therapeutic alternative to corticotropinomas, gonadotropinomas, and prolactinomas resistant to dopamine agonists. Somatostatin analogs have also shown to be useful in the treatment of other endocrine diseases (congenital hyperinsulinism, Graves' orbitopathy, diabetic retinopathy, diabetic macular edema), non-endocrine tumors (breast, colon, prostate, lung, and hepatocellular), and digestive diseases (chronic refractory diarrhea, hepatorenal polycystosis, gastrointestinal hemorrhage, dumping syndrome, and intestinal fistula).

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Section: Antiproliferative Effects In Gep-netscontrasting

confidence: 48%

Somatostatin Analogs in Clinical Practice: A Review

Gomes-Porras

Cárdenas-Salas

Álvarez-Escolá

2020

IJMS

158

136

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“…The viability of the cells treated with OCT-alginate and CTX-alginate-beads significantly decreased compared to the free OCT and CTX treatments. This result could be due to the improved solubility of the OCT-alginate and CTX-alginate-beads, which improved cell penetration for both OCT and CTX in all cell lines as the antiproliferative activity for both OCT and CTX were improved 50,51 . For example, the HCT-116 cell line had an IC 50 for OCT-alginate and CTX-alginate-beads of 5.48 µg/mL and 4.38 µg/mL vs 7.92 µg/mL and 5.21 µg/mL for free OCT and CTX, respectively.…”

Section: Determination Of the Antiproliferative Activity Of Ctx-oct Fmentioning

confidence: 99%

Cetuximab Conjugated with Octreotide and Entrapped Calcium Alginate-beads for Targeting Somatostatin Receptors

Abdellatif

Ibrahim

Amin

et al. 2020

Sci Rep

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There is a need to formulate oral cetuximab (CTX) for targeting colorectal cancer, which is reported to express somatostatin receptors (SSTRs). Therefore, coating CTX with a somatostatin analogue such as octreotide (OCT) is beneficial. Alginate was used to coat CTX to facilitate delivery to the gastrointestinal tract (GIT). This study aimed to deliver CTX conjugated with OCT in the form of microparticles as a GIT-targeted SSTR therapy. Both CTX and OCT were conjugated using a solvent evaporation method and the conjugated CTX-OCT was then loaded onto Ca-alginate-beads (CTX-OCT-Alg), which were characterized for drug interactions using differential scanning calorimetry (DSC), and Fourier transform infrared spectra (FTIR). Moreover, the morphology of formulated beads was examined using a scanning electron microscope (SEM). The drug content and release profile were studied using UV spectroscopy. Finally, in vitro cytotoxicity of all compounds was evaluated. The results showed homogenous conjugated CTX-OCT with a diameter of 0.4 mm. DSC showed a delay in the OCT peak that appeared after 200 °C due to small polymer interaction that shifted the OCT peak. Moreover, FTIR showed no prominent interaction. SEM showed clear empty cavities in the plain Ca-alginate-beads, while CTX-OCT-Alg showed occupied beads without cavities. CTX-OCT-Alg had a negligible release in 0.1 N HCl, while the CTX-OCT was completely released after 300 min in phosphate buffer pH 7.4. All formulations showed good antiproliferative activity compared with free drugs. The formulated CTX-OCT-Alg are a promising platform for targeting colorectal cancer through Git.Oral dosage forms of medications are generally a convenient dosage form for drug delivery 1,2 . However, one of the main challenges in drug delivery is to overcome gastric barriers and preventing the drug release in the stomach 3 . There was a huge increase in the development of orally delivered anti-cancer agents in the past 10 years, as a quarter of all available anti-cancer drugs are now administered orally 4 . Colorectal cancer is one of the most common forms of malignancy and the fourth most common contributor to cancer mortalities 5 . Moreover, targeting specific cells in cancer therapy provides an advantageous way to treat cancer directly 6-10 . For example, the release of drug in the colon and drug particles can be driven by octreotide (OCT) and bind to somatostatin receptors (SSTRs), which are a component of ligand-mediated targeting 8 . The inhibition effect of somatostatin (SST) analogues on tumor cells is one effective approach to cancer therapy. Moreover, SST and its analogues have open Scientific RepoRtS | (2020) 10:4736 | https://doi.org/10.1038/s41598-020-61605-y www.nature.com/scientificreports www.nature.com/scientificreports/ shown proliferative inhibition of colon cancer cell lines 11 . There are five subtypes of SSTRs expressed in colorectal cancer, and SSTR1 is the most prevalent compared to the others 12 .Cetuximab (CTX) is a recombinant monoclonal antibody drug used in the...

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“…Other factors (age and gender, location of primary tumour, surgical resection of primary tumour, presence of extrahepatic metastases, SSTR uptake, baseline levels of CgA or urinary 5-HIAA) did not appear to be predictive of response to treatment. In a previous large retrospective study from our centre evaluating predictors of PFS in a cohort of 254 treatment naive patients with NET treated with octreotide LAR, the median PFS was 37 months and liver tumour burden, higher tumour grade (grade 2) and pancreatic primaries were predictive of a shorter PFS [6].…”

Section: Discussionmentioning

confidence: 91%

“…Currently there is limited literature on factors that predict PFS in patients with NENs receiving SSAs. A recent study from our centre focused on predictive factors affecting PFS in patients with advanced NENs treated with octreotide LAR and identified several predictors of response [6]. The present study aimed to determine the median PFS and evaluate factors affecting PFS in a cohort of patients with gastroenteropancreatic (GEP) NENs treated with LAN 120 mg/month as first-line monotherapy in a tertiary centre.…”

Section: Introductionmentioning

confidence: 97%

Predictors of antiproliferative effect of lanreotide autogel in advanced gastroenteropancreatic neuroendocrine neoplasms

et al. 2019

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Purpose The antiproliferative properties of lanreotide autogel (LAN) in gastroenteropancreatic neuroendocrine neoplasms (GEP NENs) were demonstrated in the CLARINET study. However, there is limited literature regarding factors that affect progression-free survival (PFS) in patients with GEP NENs treated with LAN. Methods We identified a total of 191 treatment-naive patients with advanced GEP NENs and positive SSTR uptake on imaging (Octreoscan or 68 Gallium DOTATATE Positron Emission Tomography [ 68 GaPET]) who received first-line LAN monotherapy, albeit at various starting doses (60, 90 or 120 mg/month). A group of 102 patients who initiated treatment at the standard dose of 120 mg/month were included in the study and further evaluated by univariate and multivariate analyses to identify predictors of PFS. Results The location of tumour primary was in the small bowel in 63 (62%), pancreas in 31 (30%) and colon/rectum in 8 patients (8%). The tumours were well-differentiated, and the majority were grade 1 (52%), or 2 (38%). About 60% of cases had progressive disease at the time of treatment initiation. Most patients with available pretreatment nuclear medicine imaging (Octreoscan or 68 Ga PET) had a Krenning score of 3 (44%) or 4 (50%). The median PFS for the entire cohort was 19 months (95% CI 12, 26 months). The univariate analysis demonstrated that grade 2 tumours, progressive disease at baseline and metastatic liver disease were associated with a significantly shorter PFS, while other evaluated variables did not affect PFS at a statistically significant level. However, at multivariate analysis only the tumour grade remained statistically significant. Conclusions The current study showed that, of many evaluated variables, only the tumour grade was predictive of PFS duration and this should be considered during patient selection for treatment.

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Predictive factors of antiproliferative activity of octreotide LAR as first-line therapy for advanced neuroendocrine tumours

Cited by 26 publications

References 22 publications

Somatostatin Analogs in Clinical Practice: A Review

Somatostatin Analogs in Clinical Practice: A Review

Cetuximab Conjugated with Octreotide and Entrapped Calcium Alginate-beads for Targeting Somatostatin Receptors

Predictors of antiproliferative effect of lanreotide autogel in advanced gastroenteropancreatic neuroendocrine neoplasms

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