Treatment with cisplatin and etoposide in patients with neuroendocrine tumors

BACKGROUND. Patients with malignant endocrine pancreatic tumors (EPTs) are responsive to combinations of chemotherapy with streptozotocin and 5-fluoro -uracil/doxorubicin, whereas patients with malignant carcinoids are not. Fo r both categories of patients, alpha -interferon and/or somatostatin analog s can produce long-lasting responses. Cisplatin in combination with etoposi de has been suggested to be effective in patients with malignant neuroendoc rine carcinomas. The authors used this therapy as second-line or third-line treatment in patients with poorly differentiated and/or rapidly progressin g disease. METHODS. Thirty-six patients with histopathologically verified malignant ne uroendocrine, docrine 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 or igin. 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 dise ase. Thirty of 36 patients had received previous treatment. Etoposide was g iven at a dose of 100 mg/m(2) per day for 3 days, and cisplatin was given a t a dose of 45 mg/m(2) on Days 2 and 3 as a continuous intravenous infusion that was repeated every 4 weeks. RESULTS. Ten of 18 patients with foregut carcinoids (56%) responded radiolo gically 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 betw een patients with atypical or typical foregut carcinoids or between patient s with well differentiated or poorly differentiated endocrine pancreatic ca rcinoma. Nineteen of 36 patients (53%) experienced World Health Organizatio n (WHO) Grade 1-2 nephrotoxicity, and 23 patients (64%) suffered from WHO G rade 3-4 neutropenia. CONCLUSIONS. The combination of cisplatin and etoposide can produce signifi cant responses in patients with heavily pretreated and poorly differentiate d/ rapidly progressing neuroendocrine tumors. The toxicity is considerable, and nephrotoxicity is the dose limiting factor. (C) 2001 American Cancer S ociety.