Activity of Sunitinib in Patients With Advanced Neuroendocrine Tumors

Kulke, Matthew H.; Lenz, Heinz Josef; Meropol, Neal J.; Posey, James; Ryan, David P.; Picus, Joel; Bergsland, Emily K.; Stuart, Keith; Tye, L.; Huang, Xin; Li, Jim Z.; Baum, Charles M.; Fuchs, Charles S.

doi:10.1200/jco.2007.15.9020

Cited by 571 publications

(366 citation statements)

References 45 publications

(4 reference statements)

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“…Figure 1 outlined the selection process in detail. These trials represented three studies with sorafenib, 21,31,32 three with sunitinib, 20,33,34 three with vandetanib [35][36][37] and five with pazopanib. 2,[38][39][40][41] The characteristics of each included trial were presented in Table 2.…”

Section: Resultsmentioning

confidence: 99%

Risk of venous thromboembolic events associated with VEGFR‐TKIs: A systematic review and meta‐analysis

Min

Shen

et al. 2012

Intl Journal of Cancer

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Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) have been widely used in advanced cancers. Concerns have arisen regarding the risk of venous thromboembolism with the use of these drugs. Currently, the contribution of VEGFR-TKIs to venous thromboembolism is still unknown. We performed a meta-analysis to determine the incidence and relative risk (RR) of venous thromboembolism events (VTEs) associated with these agents. Eligible studies included phase II and III prospective trials evaluating US Food and Drug Administration approved VEGFR-TKIs (pazopanib, sunitinib, sorafenib and vandetanib), and data on VTEs were available. Overall incidence rates, RR and 95% confidence intervals (CI) were calculated employing fixed-or random-effects models depending on the heterogeneity of included trials. A total of 14 studies (4,430 patients) were selected for this meta-analysis. The incidence of VTEs related to VEGFR-TKIs was 3% (95%CI: 1.7-5.1%), and there was no statistically significant increase in the risk of VTEs for VEGFR-TKIs versus controls in overall population (RR0.912, 95%CI: 0.617-1.348, p 5 0.643). On subgroup analysis, no significant increase in the risk of VTEs was found among different VEGFR-TKIs or tumor types. No evidence of publication bias was observed. The use of VEGFRTKIs does not significantly increase the risk of VTEs, the risk of VTEs in patients with cancer is driven predominantly by tumor types, host factors and concomitant usage of anticancer agents. These results would provide important information for clinicians who use VEGFR-TKIs to treat patients with solid cancer.

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Section: Resultsmentioning

confidence: 99%

Risk of venous thromboembolic events associated with VEGFR‐TKIs: A systematic review and meta‐analysis

Min

Shen

et al. 2012

Intl Journal of Cancer

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“…At present, several clinical trials examining these treatments have been completed and several are ongoing. A substantial benefit from the use of Lanreotide or Octreotide LAR combined with a targeted drug, such as everolimus or sunitinib, has been indicated (Faiss et al, 1999;Oberg et al, 2004;Kulke et al, 2008;Rinke et al, 2009;Yao et al, 2010;Raymond et al, 2011;Yao et al, 2011). These trials are mainly targeting disease progression.…”

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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“…Phase 1 and phase 2 clinical trials that use these agents in patients with advanced carcinoid tumors have demonstrated promising results. Recent reports have suggested that bevacizumab, 37 RAD001 (everolimus), 38 and sunitinib 39 have efficacy in advanced carcinoid tumors. However, to our knowledge, these studies have not been restricted to pulmonary carcinoid tumors, and in fact they tend to be under-represented in clinical trials.…”

Section: Prognosis and Survivalmentioning

confidence: 99%

“…The median time to disease progression, however, was only 10.2 months. 39 Radiotherapy alone has been gaining attention as an adjuvant therapy in patients with carcinoid tumors; however, randomized studies are limited by the relative rarity of carcinoid tumors. Reported studies have shown possible benefit, particularly in patients with lymph node-positive disease.…”

Section: Prognosis and Survivalmentioning

confidence: 99%

Pulmonary neuroendocrine/carcinoid tumors

Bertino

Confer

Colonna

et al. 2009

Cancer

131

123

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Neuroendocrine tumors are a unique malignant neoplasm that can arise from the respiratory tree. Although well-differentiated bronchial neuroendocrine tumors (also called carcinoid tumors) are reported to account for approximately 25% of all neuroendocrine tumors, they represent only 1% to 2% of all lung cancers. The epidemiology, clinical behavior, and treatment of neuroendocrine carcinoid tumors differ significantly from other lung malignancies. In this article, the recent data regarding these tumors were reviewed with attention to the treatment modalities used. Although conventional cytotoxic therapy has not been reported to demonstrate much promise in this entity over the past 4 decades, newer molecular targeted agents including those that targeted angiogenesis and the mammalian target of rapamycin (mTOR) Well-differentiated neuroendocrine, or carcinoid, tumors are a unique class of malignancies capable of producing hormones identical to those from the nervous system. Although the first carcinoid tumor described was in the ileum, neuroendocrine malignancies are a family of malignancies found throughout the body. Tumors of the bronchial tree in particular account for approximately 25% of all well-differentiated neuroendocrine tumors (Table 1). [1][2][3] However, compared with other malignancies of the bronchoalveolar tree, these well-differentiated neuroendocrine tumors are rare, accounting for only 1% of all lung cancers. 3 The pathologic spectrum of neuroendocrine malignancies ranges from low-grade carcinoid to aggressive small cell lung cancer. The low-grade and intermediate-grade neuroendocrine malignancies, also known as typical and atypical carcinoid, will be the focus of this review. The distinct features of this malignancy include its pathologic characteristics, clinical behavior, epidemiology, prognosis, and treatment.

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Activity of Sunitinib in Patients With Advanced Neuroendocrine Tumors

Abstract: Sunitinib has antitumor activity in pancreatic neuroendocrine tumors; its activity against carcinoid tumors could not be definitively determined in this nonrandomized study. Randomized trials of sunitinib in patients with neuroendocrine tumors are warranted.

Cited by 571 publications

References 45 publications

Risk of venous thromboembolic events associated with VEGFR‐TKIs: A systematic review and meta‐analysis

Risk of venous thromboembolic events associated with VEGFR‐TKIs: A systematic review and meta‐analysis

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

Pulmonary neuroendocrine/carcinoid tumors

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