Treatment with cisplatin and etoposide in patients with neuroendocrine tumors

Abstract

BACKGROUND 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, α‐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. METHODS 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/m2 per day for 3 days, and cisplatin was given at a dose of 45 mg/m2 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 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. CONCLUSIONS 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. Cancer 2001;92:1101–7. © 2001 American Cancer Society.

Neuroendocrine tumours.

“…Indeed, in undifferentiated NETs, the chemosensitivity is similar to that of small cell carcinoma of the lung. Various combinations of chemotherapy have been used, including streptozotocin and adriamycin in well-differentiated pancreatic NETs (Moertel et al 1992), lomustine (CCNU) and 5-fluorouracil (5FU) in advanced NETs (Kaltsas et al 2002), etoposide (VP16) and cisplatin (CDDP) (Moertel et al 1991, Fjallskog et al 2001 in poorly-differentiated, aggressive NETs giving response rates of 50 to 56% and benefitting pancreatic NETs and foregut carcinoids most. However, toxicity rates were high.…”

Poorly Differentiated Neuroendocrine Carcinoma of the Pancreas Responsive to Combination Therapy with Gemcitabine and S-1

“…The genetic, pathological and clinical features of PDNECs overlap with those of small cell lung cancer, thereby combined chemotherapy with cisplatin and etoposide has been widely used for extrapulmonary PD-NECs (18,19). In addition, several clinical studies reported that this combination was effective for improving survival time of patients with metastatic NECs of the GI tract (18,20). However, to the best of our knowledge, only one study examined the efficacy of this treatment as first line chemotherapy for unresectable PD-NECs of the pancreas and hepatobiliary tract (22), but this combination therapy exerts only marginal antitumor activity and severe toxicity, and resulted in median progression-free survival and overall survival of 1.8 and 5.8 months, respectively.…”

Is there a role for platinum chemotherapy in the treatment of patients with hormone‐refractory prostate cancer?

“…Two trials of cisplatin and etoposide in 45 and 32 evaluable patients produced response rates of 67% and 53%, respectively. 85,86 Whether there is a distinct clinical phenotype of a more NE-differentiated cancer remains unknown. Patients with poorly differentiated prostate cancers who are diagnosed later with unusual visceral metastases, such as hepatic or brain, are often assumed to have some component of NE differentiation but rarely undergo biopsy.…”