Therapeutic Options for Gastrointestinal Carcinoids

Modlin, Irvin M.; Latich, Igor; Kidd, Mark; Zikusoka, Michelle N.; Eick, Geeta

doi:10.1016/j.cgh.2005.12.008

Cited by 136 publications

(101 citation statements)

References 189 publications

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“…Thus, a larger sample size is needed for a more precise conclusion regarding the positive rates of the three immunohistochemical staining markers among the three grades. Among the many therapeutic options for NENs, surgery is the treatment of choice (Plockinger et al, 2004;Modlin et al, 2006;Oberg et al, 2009;Yalcin, 2011). A variety of operations is available to reduce the tumor load and improve survival, and the extent of surgical resection depends on the tumor size and origin.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological Features and Prognosis of Gastroenteropancreatic Neuroendocrine Tumors: Analysis from a Single-institution

Zeng

Liu²,

Wu³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: The gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) is the most common type of neuroendocrine neoplasm. We summarized data in our centre to investigate the clinicopathological features, diagnostic methods, therapeutic approaches and prognosis for this neoplasm to increase knowledge of this disease in Asian populations. Method: A total of 122 patients treated at Sun Yet-san Memorial Hospital of Sun Yat-sen University between January 2000 and December 2011 were analyzed retrospectively. Results: Pancreas was the most common site of involvement (65/122, 53.3%); this disease has no special symptoms; positive rates of chromogranin A (CgA) and synaptophysin (Syn) were 81.1% and 87.7%, respectively. The positive rate of Syn had statistical difference among the three grades, but not CgA. Some 68 patients had G1 tumors, 32 G2 tumors and 22 G3 tumors, and Chi-square test showed that higher grading was correlated with worse prognosis (χ 2 =32.825, P=0.0001). A total of 32 patients presented with distant metastasis, and 8 cases emerged during following up. Cox proportional hazards regression modeling showed that the tumor grade (P=0.01), lymphatic metastasis (P=0.025) and distant metastasis (P=0.031) were predictors of unfavorable prognosis. The overall 5-year survival rate was 39.6%, the 5-year survival rate of G1 was 55.7%, and the G2 and G3 were 34.2% and 0%, respectively.Conclusions: The incidence of gastroenteropancreatic neuroendocrine tumors has risen over the last 12 years. All grades of these diseases metastasize readily, and further research regarding the treatment of patients after radical surgery is needed to prolong disease-free survival.

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Section: Discussionmentioning

confidence: 99%

Clinicopathological Features and Prognosis of Gastroenteropancreatic Neuroendocrine Tumors: Analysis from a Single-institution

Zeng

Liu²,

Wu³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…Nevertheless, treatment of gastrointestinal carcinoids with somatostatin analogues targeting SSTR3, like octreotide or octreotides labeled with radionuclides ( 111 In, 90 Y, 177 Lu), have proved to efficiently inhibit cell growth and induce apoptosis (24). Therefore, after 213 Bi-d9MAb therapy of diffuse-type gastric cancer in the nude mouse model (8), up-regulation of SSTR3 expression could be exploited to enhance therapeutic efficacy via additional administration of radiolabeled octreotide.…”

Section: Discussionmentioning

confidence: 99%

213Bi-induced death of HSC45-M2 gastric cancer cells is characterized by G2 arrest and up-regulation of genes known to prevent apoptosis but induce necrosis and mitotic catastrophe

Seidl¹,

Port

Gilbertz

et al. 2007

Molecular Cancer Therapeutics

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Tumor cells are efficiently killed after incubation with A-emitter immunoconjugates targeting tumor-specific antigens. Therefore, application of A-emitter immunoconjugates is a promising therapeutic option for treatment of carcinomas that are characterized by dissemination of single tumor cells in the peritoneum like ovarian cancer or gastric cancer. In diffuse-type gastric cancer, 10% of patients express mutant d9-E-cadherin on the surface of tumor cells that is targeted by the monoclonal antibody d9MAb. Coupling of the A-emitter 213 Bi to d9MAb provides an efficient tool to eliminate HSC45-M2 gastric cancer cells expressing d9-E-cadherin in vitro and in vivo. Elucidation of the molecular mechanisms triggered by A-emitters in tumor cells could help to improve strategies of A-emitter radioimmunotherapy. For that purpose, gene expression of 213 Bi-treated tumor cells was quantified using a real time quantitative-PCR low-density array covering 380 genes in combination with analysis of cell proliferation and the mode of cell death. We could show that 213 Bi-induced cell death was initiated by G 2 arrest; up-regulation of tumor necrosis factor (TNF), SPHK1, STAT5A, p21, MYT1, and SSTR3; and down-regulation of SPP1, CDC25 phosphatases, and of genes involved in chromosome segregation. Together with morphologic changes, these results suggest that 213 Bi activates death cascades different from apoptosis. Furthermore, 213 Bitriggered up-regulation of SSTR3 could be exploited for improvement of the therapeutic regimen. [Mol Cancer Ther 2007;6(8):2346 -59]

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“…However, expression of multiple sst subtypes is observed in NETs (Hofland & Lamberts 2003). Although octreotide LAR therapy effectively reduces the symptoms of carcinoid syndrome in the majority of patients (Rubin et al 1999, Modlin et al 2006), a considerable number of patients will experience an escape from response within months to several years of treatment, whereupon symptoms may return, and the prognosis for these patients is poor (Hofland et al 2005). Mechanisms by which this desensitization to currently available sst analogs may occur include sst 2 internalization and downregulation on tumor cells, over-expression of other sst receptor subtypes (Ronga et al 1995, Li et al 2004, Schmid & Schoeffter 2004, or other unknown mechanisms.…”

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confidence: 99%

Pasireotide (SOM230) shows efficacy and tolerability in the treatment of patients with advanced neuroendocrine tumors refractory or resistant to octreotide LAR: results from a phase II study

Kvols¹,

Öberg²,

O'Dorisio³

et al. 2012

Endocrine-Related Cancer

176

116

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Pasireotide (SOM230) is a novel multireceptor-targeted somatostatin (sst) analog with high binding affinity for sst receptor subtype 1, 2, 3 (sst 1,2,3 ) and sst 5 . Because of this binding profile, pasireotide may offer symptom control in patients with neuroendocrine tumors (NETs) and carcinoid syndrome no longer responsive to octreotide LAR. This was a phase II, open-label, multicenter study of pasireotide in patients with advanced NET whose symptoms of carcinoid syndrome (diarrhea/flushing) were inadequately controlled by octreotide LAR. Patients received s.c. pasireotide 150 mg twice daily (bid), escalated to a maximum dose of 1200 mg bid until a clinical response was achieved. Forty-four patients were evaluated for efficacy and 45 for tolerability. Pasireotide 600-900 mg s.c. bid effectively controlled the symptoms of diarrhea and flushing in 27% of patients. Evaluation of tumor response in 23 patients showed 13 with stable disease and ten with progressive disease at study end. The most common drug-related adverse events were nausea (27%), abdominal pain (20%), weight loss (20%), and hyperglycemia (16%) and most were of mild or moderate severity. Pasireotide 600-900 mg s.c. bid was effective and generally well tolerated in controlling the symptoms of carcinoid syndrome in 27% of patients with advanced NET refractory or resistant to octreotide LAR therapy.

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Therapeutic Options for Gastrointestinal Carcinoids

Cited by 136 publications

References 189 publications

Clinicopathological Features and Prognosis of Gastroenteropancreatic Neuroendocrine Tumors: Analysis from a Single-institution

Clinicopathological Features and Prognosis of Gastroenteropancreatic Neuroendocrine Tumors: Analysis from a Single-institution

213Bi-induced death of HSC45-M2 gastric cancer cells is characterized by G2 arrest and up-regulation of genes known to prevent apoptosis but induce necrosis and mitotic catastrophe

Pasireotide (SOM230) shows efficacy and tolerability in the treatment of patients with advanced neuroendocrine tumors refractory or resistant to octreotide LAR: results from a phase II study

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