The role of systemic chemotherapy in the treatment of patients with metastatic neuroendocrine tumors is controversial. While combination regimens containing cisplatin and etoposide have activity against more aggressive neuroendocrine tumor variants, such regimens appear to have little efficacy in patients with well-differentiated neuroendocrine tumor subtypes. The combination of irinotecan and cisplatin is active both against small cell lung cancer and in upper gastrointestinal malignancies but has not been prospectively evaluated in patients with metastatic neuroendocrine tumors. We therefore assessed the efficacy of an irinotecan/cisplatin combination in patients with this disease. Eighteen patients with metastatic neuroendocrine tumors (excluding small cell carcinoma) were treated with irinotecan, 65 mg/m2, and cisplatin, 30 mg/m2, administered weekly for 2 of every 3 weeks. Patients were followed for evidence of toxicity, response, and survival. The toxicities associated with this regimen were mild and included myelosuppression, nausea, and diarrhea. Only one radiologic response was observed among four patients with poorly differentiated neuroendocrine tumors. No radiologic responses were observed in 14 patients with well-differentiated tumors. The median overall survival duration of patients treated with this regimen was 11.4 months. We conclude that while the combination of irinotecan and cisplatin may have activity in aggressive neuroendocrine tumor subtypes, this combination is inactive in patients with well-differentiated neuroendocrine tumors.
"The authors concluded that while CapOx may be a good option for well-differentiated NET, it may not be a good choice for first-line treatment of high-grade NET when compared to historical data of patients treated with cisplatin and VP-16. However, the RR achieved with cisplatin and VP-16 combination has been inconsistent, varying according to the series between 14% and 67%.27,28 Our study included 9 patients with grade 3 NET: 6 received CapOx as first-line and 3 as second or further lines, with a median of 8 cycles. "
[Show abstract][Hide abstract] ABSTRACT: The role of chemotherapy in well differentiated neuroendocrine tumors (NET) has been questioned. It was recently demonstrated that everolimus and sunitinib have activity in low and intermediate grade pancreatic NET. The aim of this study was to evaluate the activity of capecitabine and oxaliplatin (CapOx) combination in treating NET in an unselected population. In this regard, we retrospectively evaluated 24 patients diagnosed with metastatic NET treated with CapOx at two Brazilian institutes that are reference centers in cancer care. Tumor response was measured by RECIST criteria. Median age at diagnosis was 56 years, 71% had ECOG 0 or 1, the majority of tumors were primary from pancreas (67%) followed by lung (17%), and 29% were functional. According to WHO classification criteria, 25% were grade 1, 37.5% grade 2 and 37.5% grade 3. Most patients received CapOx as second-line therapy, with a median of 6 cycles. Twenty-nine percent of patients had partial response by RECIST criteria. No association was observed between response rate and tumor grade, primary site or line of CapOx. The median time to progression was 9.8 months and median time to treatment failure was 12.1 months. Seventy-five percent of patients are alive at the time of this analysis; therefore, median overall survival was not reached. The CapOx combination was shown to be active in an unselected population with metastatic NET and may be a good platform for the incorporation of the newer molecular targeted agents being investigated for the treatment of this entity.
"Following the same rationale, cisplatin in combination with irinotecan was tested in patients with advanced extrapulmonary PDNEC in small phase II trials, with response rate achieving approximately 40% to 50% and no activity in patients with well-differentiated neuroendocrine tumors.12-14 However, the efficacy and safety of this combination has not been evaluated in a non-selected population of PDNEC patients. "
[Show abstract][Hide abstract] ABSTRACT: Extrapulmonary poorly differentiated neuroendocrine carcinoma (PDNEC) is a rare and highly aggressive neoplasm for which the optimal chemotherapy remains unclear. The objective of this study was to evaluate the outcomes of patients with PDNEC treated with cisplatin and irinotecan (IP) and perform a review of the literature. From 2008 to 2012, patients with advanced PDNEC (Ki67≥20%) who received the IP combination were selected for analysis. Radiologic responses were determined through Response Evaluation Criteria In Solid Tumors criteria. Twenty-eight patients were included. The median age at diagnosis was 57 years and the most common presentation was pancreatic PDNEC. Twenty-five patients (89%) received chemotherapy with cisplatin and irinotecan and three received carboplatin and irinotecan. Forty-six percent of the patients achieved objective response and the median time to tumor progression was 3.7 months. The median overall survival was 11.7 months. Thirteen patients (46%) had treatment interruptions or dose reductions due to grade 3/4 toxicity. This retrospective cohort of advanced extrapulmonary PDNEC patients suggests that the IP combination is feasible and resulted in similar response rate and median survival to other treatments previously reported.
[Show abstract][Hide abstract] ABSTRACT: Gastrointestinal carcinoid tumors are rare. They constitute approximately two-thirds of all carcinoid tumors. Numerous therapeutic modalities have been used to treat metastatic carcinoids, including hepatic artery embolization and chemoembolization, surgical resection, radio-frequency ablation, chemotherapy, and the use of Octreotide combined with interferon-alpha. We report a case of sustained symptomatic control in a patient with cecal carcinoid metastatic to the liver using a combination of gemcitabine and carboplatin (GC). We believe that this case illustrates the potential clinical value of the GC combination in the setting of metastatic gastrointestinal carcinoid tumor. Larger clinical trials will be required to fully elucidate the clinical efficacy and side effects of similar regimens. Copyright 2007 OPUS 12 Foundation, Inc.
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