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      Poorly differentiated carcinomas of the foregut (gastric, duodenal and pancreatic).

      Neuroendocrinology
      Carcinoma, diagnosis, epidemiology, therapy, Duodenal Neoplasms, Humans, Pancreatic Neoplasms, Stomach Neoplasms

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          Treatment of neuroendocrine carcinomas with combined etoposide and cisplatin. Evidence of major therapeutic activity in the anaplastic variants of these neoplasms.

          Forty-five patients with metastatic neuroendocrine tumors were treated with a regimen of etoposide 130 mg/m2/d for 3 days plus cisplatin 45 mg/m2/d on days 2 and 3. Both drugs were given by continuous intravenous infusion. Among 27 patients with well-differentiated carcinoid tumors or islet cell carcinomas, only two partial objective tumor regressions were observed (7%). Among 18 patients prospectively classified as having anaplastic neuroendocrine carcinomas, however, there were nine partial regressions and three complete regressions, an overall regression rate of 67%. For anaplastic disease, the median duration of regression was 8 months (range to 21 months). Tumor response was unrelated to primary site, endocrine hyperfunction, or prior therapy experience. The median survival of all patients with anaplastic tumors was 19 months; this seemed favorable when considering the small experiences with these rare tumors reported in the literature. Toxicity, which was severe for most patients, consisted primarily of vomiting, leukopenia, thrombocytopenia, anemia, alopecia, and neuropathy. The anaplastic neuroendocrine tumor is strongly responsive to therapy with combined etoposide and cisplatin. Patients with undifferentiated carcinomas, originating in typical neuroendocrine tumor sites (small and large bowel, pancreas, and stomach) or of unknown origin, who have consistent histologic findings by light microscopy should be evaluated for this possibility with appropriate immune staining or electron microscopy.
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            Gastric carcinoids and neuroendocrine carcinomas: pathogenesis, pathology, and behavior.

            The goal of this study was to provide information of prognostic value for gastric endocrine tumors. A total of 205 gastric endocrine tumors have been studied: 193 well differentiated tumors [2 gastrin cell tumors, 191 enterochromaffin-like (ECL) cell tumors] and 12 poorly differentiated carcinomas. Subtyping of ECL cell tumors (carcinoids) resulted in 152 associated with chronic atrophic gastritis (CAG) (type 1); 12 associated with hypertrophic gastropathy (HG) due to Zollinger-Ellison syndrome with multiple endocrine neoplasia type I (type 2), and 27 with no specific association (type 3, sporadic). Type 1 cases occurred most often in female (108 of 152), elderly (mean 63 years) patients, with no tumor-related death at an overall mean follow-up of 53 months. The 12 type 2 cases were equally distributed between the sexes (six of each), with a mean age of 45 years; there was one tumor-related death (49 months after diagnosis) and an overall mean survival of 84 months. Type 3 cases were mostly in men (20 of 27), with a mean age of 55 years; there were seven tumor-related deaths at a mean follow-up of 28 months. Poorly differentiated neuroendocrine carcinomas were observed in elderly patients (mean 63 years, range 41-76 years) of both sexes, with nine tumor-related deaths and a mean survival of 7 months. It was concluded that correct clinicopathologic subtyping may predict the clinical behavior of gastric endocrine tumors.
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              Treatment with cisplatin and etoposide in patients with neuroendocrine tumors.

              Patients with malignant endocrine pancreatic tumors (EPTs) are responsive to combinations of chemotherapy with streptozotocin and 5-fluorouracil/doxorubicin, whereas patients with malignant carcinoids are not. For both categories of patients, alpha-interferon and/or somatostatin analogs can produce long-lasting responses. Cisplatin in combination with etoposide has been suggested to be effective in patients with malignant neuroendocrine carcinomas. The authors used this therapy as second-line or third-line treatment in patients with poorly differentiated and/or rapidly progressing disease. Thirty-six patients with histopathologically verified malignant neuroendocrine tumors were included: Eighteen tumors were of foregut origin, of which 5 were atypical, and 15 tumors were EPTs, of which 4 were poorly differentiated endocrine carcinomas. Three tumors were of midgut origin. The median patient age was 47.5 years. The median duration of disease from the time of diagnosis was 12 months. All patients had metastatic disease. Thirty of 36 patients had received previous treatment. Etoposide was given at a dose of 100 mg/m(2) per day for 3 days, and cisplatin was given at a dose of 45 mg/m(2) on Days 2 and 3 as a continuous intravenous infusion that was repeated every 4 weeks. Ten of 18 patients with foregut carcinoids (56%) responded radiologically and/or biochemically, with a median duration of 9 months; and 7 of 14 patients with EPTs (50%) responded radiologically and/or biochemically, with a median duration of 9 months. No difference in response was seen between patients with atypical or typical foregut carcinoids or between patients with well differentiated or poorly differentiated endocrine pancreatic carcinoma. Nineteen of 36 patients (53%) experienced World Health Organization (WHO) Grade 1-2 nephrotoxicity, and 23 patients (64%) suffered from WHO Grade 3-4 neutropenia. The combination of cisplatin and etoposide can produce significant responses in patients with heavily pretreated and poorly differentiated/rapidly progressing neuroendocrine tumors. The toxicity is considerable, and nephrotoxicity is the dose limiting factor. Copyright 2001 American Cancer Society.
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                Author and article information

                Journal
                17312381
                10.1159/000098013

                Chemistry
                Carcinoma,diagnosis,epidemiology,therapy,Duodenal Neoplasms,Humans,Pancreatic Neoplasms,Stomach Neoplasms

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