Fluorouracil, Doxorubicin, and Streptozocin in the Treatment of Patients With Locally Advanced and Metastatic Pancreatic Endocrine Carcinomas

Kouvaraki, Maria A.; Ajani, Jaffer A.; Hoff, Paulo M.; Wolff, Robert A.; Evans, Douglas B.; Lozano, Richard D.; Yao, James C.

doi:10.1200/jco.2004.04.024

Cited by 538 publications

(335 citation statements)

References 42 publications

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“…According to published studies, several chemotherapeutic regimens, most of which are either platinum based or fluorouracil based, are suggested. However, a definitive guideline is still unavailable (Mitry et al, 1999;Fjallskog et al, 2001;Kouvaraki et al, 2004;Sun et al, 2005;Hainsworth et al, 2006). In our study, all regimens utilized were either the platinum based or fluorouracil based, but the number of cases for cytotoxic chemotherapy was too small to obtain a statistically significant conclusion.…”

Section: Discussionmentioning

confidence: 65%

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: 65%

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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“…Radiological degree of liver involvement in NETs is a welldocumented prognostic factor (Janson et al, 1997;Madeira et al, 1998;Kouvaraki et al, 2004). Number of liver metastases (more than four) and proportion of liver volume involved (more than 75%) have been shown to correlate with poorer OS (Janson et al, 1997;Kouvaraki et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Number of liver metastases (more than four) and proportion of liver volume involved (more than 75%) have been shown to correlate with poorer OS (Janson et al, 1997;Kouvaraki et al, 2004). We postulated that serum biochemical parameters such as gammaGT, ALT and bilirubin might provide prognostic information via a functional assessment of liver impairment.…”

Section: Discussionmentioning

confidence: 99%

The prognostic role of WHO classification, urinary 5-hydroxyindoleacetic acid and liver function tests in metastatic neuroendocrine carcinomas of the gastroenteropancreatic tract

et al. 2007

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The World Health Organisation (WHO) classification (2000) is widely used to classify neuroendocrine carcinomas (NECs), yet its prognostic value needs to be confirmed. In this study, patients with metastatic NECs (n ¼ 119) were classified according to WHO guidelines into well differentiated and poorly differentiated (WDNECs and PDNECs). Histological differentiation based on WHO criteria had the highest impact on overall survival (OS) (PDNECs : WDNECs hazard ratio (HR) ¼ 4.02, P ¼ 0.02); however, PDNECs represented only a small percentage of patients (8%). In a WDNEC-restricted analysis, abnormal liver function tests (LFTs) and elevated urinary 5-hydroxyindoleacetic acid (u5HIAA) were independent prognostic factors for survival (HR ¼ 2.65, P ¼ 0.006 and HR ¼ 2.51, P ¼ 0.003, respectively) and were used to create a WDNEC-specific prognostic model (low risk ¼ both normal, intermediate risk ¼ one of them abnormal, high risk ¼ both abnormal). Low-risk WDNECs had the most favourable prognosis (median OS, mOS 8.1 years), which was significantly better compared to both intermediate-risk and high-risk WDNECs (mOS 3.2 and 1.4 years, with P ¼ 0.01 and Po0.001, respectively). High-risk WDNECs displayed the shortest OS (1.3 years), which was similar to that of PDNECs (P ¼ 0.572). This analysis supports the prognostic value of WHO classification for metastatic NECs arising from the gastroenteropancreatic tract; however, risk stratification using readily available u5HIAA and LFTs may be necessary for the heterogeneous group of WDNECs.

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“…Streptozocin (Table 1) [1][2][3][4][5][6][7][8][9][10][11][12][13][14] Streptozocin is a nitrosourea alkylating agent that is known to be taken up into cells by the glucose transport protein GLUT2 and to cause cell damage. Because GLUT2 is strongly expressed in pancreatic beta cells, streptozocin has been widely used to create animal models of diabetes mellitus.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic chemotherapy for pancreatic neuroendocrine tumors

Okusaka¹,

Ueno²,

Morizane³

et al. 2015

J Hepato Biliary Pancreat

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Advanced neuroendocrine tumors are incurable, and most patients will succumb to the disease. Chemotherapies with cytotoxic agents such as streptozocin, 5-fluorouracil, or temozolomide have been frequently used as drug therapies for neuroendocrine tumors. Streptozocin, which is the only approved cytotoxic agent available for the treatment of this disease in many countries, has been considered a key agent for the treatment of advanced neuroendocrine tumors based on the results of phase III studies. However, the widespread acceptance of streptozocin-based chemotherapy for this indication has been limited by concerns regarding toxicity. Recent prospective and retrospective studies showed the promising activity of a temozolomide-based regimen, although an adequate prospective controlled study defining the role of temozolomide in the treatment of neuroendocrine tumors is lacking. The promising activity of cytotoxic agents awaits confirmation; solid evidence-based recommendations and treatment decisions are needed for the optimal use of chemotherapy against this disease.

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Fluorouracil, Doxorubicin, and Streptozocin in the Treatment of Patients With Locally Advanced and Metastatic Pancreatic Endocrine Carcinomas

Abstract: Patients with locally advanced or metastatic PEC who are treated with FAS may have a reasonable RR, and responders may experience longer PFS and OS. The volume of metastases in the liver is the most important predictor of outcome.

Cited by 538 publications

References 42 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

The prognostic role of WHO classification, urinary 5-hydroxyindoleacetic acid and liver function tests in metastatic neuroendocrine carcinomas of the gastroenteropancreatic tract

Cytotoxic chemotherapy for pancreatic neuroendocrine tumors

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