A phase II trial of irinotecan and cisplatin in patients with metastatic neuroendocrine tumors

Massachusetts General Hospital, Boston, Massachusetts, United States
Digestive Diseases and Sciences (Impact Factor: 2.55). 07/2006; 51(6):1033-8. DOI: 10.1007/s10620-006-8001-3
Source: PubMed

ABSTRACT 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.

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    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.
    Rare tumors 07/2013; 5(3):e39. DOI:10.4081/rt.2013.e39
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    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.
    Rare tumors 07/2013; 5(3):e35. DOI:10.4081/rt.2013.e35
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    ABSTRACT: The impact of somatostatin receptor type 2 (SSTR-2a) expression levels on outcomes in patients with pancreatic neuroendocrine tumors (PNETs) has not been evaluated. Correlations between clinicopathologic characteristics, including SSTR-2a expression and outcomes, were retrospectively studied in 79 patients with pancreatic neuroendocrine tumors (PNETs). The SSTR-2a score was 0 in 27% of patients, 1 in 24% of patients, 3 in 30% of patients, and 4 in 18% of patients. The overall survival rate was 87% at 1 year, 77% at 3 years, and 71% at 5 years. On univariate analysis, a pancreatic tumor that measured ≥20 mm in greatest dimension, stage IV disease, vascular invasion, neuroendocrine carcinoma (NEC), and an SSTR-2a score of 0 were associated significantly with poor outcomes. On multivariate analysis, NEC (P = .000; hazard ratio, 28.8; 95% confidence interval, 7.502-111.240) and an SSTR-2a score of 0 (P = .001; hazard ratio, 3.611; 95% confidence interval, 1.344-9.702) were related independently to poor outcomes. The current analysis of prognostic factors in patients with PNETs demonstrated that NEC and an SSTR-2a score of 0 both were significant independent predictors of poor outcomes. The results suggest that the assessment of SSTR-2a may facilitate the selection of treatment regimens and the prediction of outcomes. Because a considerable proportion of patients with NEC have SSTR-2a-positive tumors, further analyses of the usefulness of somatostatin analogues are warranted in patients who have SSTR-2a-positive NEC. Cancer 2013. © 2013 American Cancer Society.
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