Phase II study of continuous infusion fluorouracil and interferon alfa-2b in the palliation of malignant neuroendocrine tumors.

Andreyev, H. J. N.; Scott-Mackie, P.; Cunningham, David; Nicolson, V; Norman, A.; Badve, Sunil; Iveson, A.; Nicolson, M. C.

doi:10.1200/jco.1995.13.6.1486

Cited by 40 publications

(14 citation statements)

References 16 publications

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“…[12][13][14][15] Unfortunately, combination chemotherapy has not significantly improved the outlook for advanced carcinoids, although the response rate varies between 20% and 40%. 16,17 Due to the limited efficacy and substantial toxicity of previous treatment regimens, we assessed the efficacy and adverse event rate of TOPA. Unfortunately, we have shown that TOPA at this dose has little antitumor efficacy in patients with carcinoid and islet cell tumors.…”

Section: Discussionmentioning

confidence: 99%

Topotecan in Patients With Advanced Neuroendocrine Tumors

Ansell

Mahoney

Green

et al. 2004

American Journal of Clinical Oncology

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New agents with antitumor activity in neuroendocrine tumors are sorely needed. We therefore conducted a phase II study of topotecan (TOPA) 1.5 mg/m2/d for 5 days every 3 weeks in 22 patients with advanced carcinoid and islet cell tumors. Severe neutropenia in 8 of 11 patients (72%) prompted a 30% dose reduction of TOPA to 1.05 mg/m2 for the final 11 patients enrolled. No objective responses were observed. Eighteen patients have progressed and 14 have died. The median time to progression was 4.2 months (95% CI: 2.9-6.5) and the median survival was 1.9 years (95% CI: 0.63-2.3). Hematologic adverse events were significant, with 16 of 22 patients developing grade IV neutropenia; however, there were no septic deaths. Nonhematologic adverse events were infrequent and were not dose limiting. In conclusion, further studies of this schedule of TOPA in this patient population are not recommended due to the lack of tumor response and significant hematologic toxicity.

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Section: Discussionmentioning

confidence: 99%

Topotecan in Patients With Advanced Neuroendocrine Tumors

Ansell

Mahoney

Green

et al. 2004

American Journal of Clinical Oncology

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“…In the absence of randomised trials, this treatment strategy was suggested as an alternative in patients who do not tolerate the previous treatment with IFNa. The role of IFNa in combination with chemotherapy in high-grade NETs has been initially studied in 25 patients with rapidly progressive tumours in combination with a continuous fluorouracil infusion (41). Acceptable results were obtained with an ORR of 41.6% and a median duration of response of 20 months; but tolerance was disappointing in this and following trials to justify further investigation at that time.…”

Section: Interferon Alphamentioning

confidence: 99%

GEP–NETs UPDATE: Biotherapy for neuroendocrine tumours

Alonso‐Gordoa

Capdevila

Grande

2015

European Journal of Endocrinology

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Neuroendocrine tumours (NETs) represent a less frequent and heterogeneous group of tumours, which has experienced, in recent years, a significant increase in effective therapeutic possibilities overcoming the disappointing results from chemotherapy. Initial improvements in treatment strategies came from somatostatin analogues (SSAs) that have widely demonstrated a significant improvement in symptomatic relief and tumour control growth by a complex mechanism of action over cell survival, angiogenesis and immunomodulation. Recent investigations have pointed out novel SSAs with a wider binding profile (pasireotide), chimeric molecules against somatostatin receptors and dopamine receptors and the combination with targeted agents, such as mTOR inhibitors or antiangiogenic agents. Immunotherapy is the second cornerstone in NET treatment and has been represented with interferon alpha for a long time, with a demonstrated activity on tumour and clinical response. Its less manageable adverse events have limited its usage. However, different checkpoints in immune system regulation have been effectively targeted in different solid tumours, and novel approaches are currently arising in NETs. In conclusion, biotherapy remains an active treatment strategy for initial approach in patients with NETs. Further investigation on patients' selection, molecular profiles, treatment sequence or combination and optimisation of current and novel biotherapy agents is required.

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“…Therefore, other combinations have also been examined and apart from a 40% objective response rate for patients with midgut carcinoids observed using doxorubicin and streptozotocin in a phase II study [24], no other reliable cytotoxic regimen has been found for patients with advanced or metastatic disease of midgut origin. The association of cytotoxics with interferon has also been investigated with largely poor outcome success apart from one study by Andreyev et al [25]who demonstrated a 47% objective response using a combination of interferon with continuous infusion of 5-FU; response duration lasted 21 months. The excellent, and reproducible, results obtained with chemo- embolisation in patients with hepatic metastases and carcinoid syndrome (tumour response rates of approximately 40–50% and excellent control of symptoms) [26]argue for its use in such patients with liver metastases.…”

Section: Well-differentiated Gep Tumours Of Midgut Originmentioning

confidence: 99%

Chemotherapy for Gastro-Enteropancreatic Endocrine Tumours

et al. 2004

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Despite similar histological and morphological aspects, gastro-enteropancreatic (GEP) endocrine tumours represent a heterogeneous group of tumours with varying clinical expression depending on tumour type (functional or not), origin and extension, but also on histological differentiation and proliferative capacity. The natural history of well-differentiated tumours is often favourable without treatment and GEP endocrine tumours may remain indolent for many years. Chemotherapy may however be indicated in the presence of symptomatic non-progressive disease (progression evaluated over 3–6 months). In contrast, poorly differentiated GEP endocrine tumours are frequently aggressive and early treatment is required. Accurate staging is mandatory and where surgery is possible (even in the event of limited metastatic disease), this option should be re-evaluated in a multidisciplinary approach. Approximately 2/3 of malignant GEP tumours are metastatic at discovery and surgery is possible in a minority of patients; therefore, chemotherapy, with/without other strategies (e.g. local ablation), is frequently indicated in patients with symptomatic, bulky or progressive disease. For well-differentiated pancreatic tumours, the reference association is Adriamycin with streptozotocin yielding objective responses (OR) in 40–60% of patients. Prolonged treatment is limited due to potential cardiotoxicity of Adriamycin and standard 2nd-line regimens are not of proven efficacy; thus, other treatment modalities are usually additionally required (e.g. chemo-embolisation). A significant OR may render a small number of patients secondarily amenable to surgery. Published series evaluating chemotherapy for midgut endocrine tumours are outdated and disappointing. Objective response rates with combined associations (including either 5-fluorouracil and/or streptozotocin) rarely exceed 20% and where possible, chemo-embolisation for hepatic metastases combined with somatostatin analogues (± interferon) should be preferred. Poorly differentiated GEP tumours are generally aggressive tumours with metastases at diagnosis and tend to progress rapidly. Surgery is rarely possible and ineffective even in locally advanced disease due to a high risk of recurrence. Chemotherapy, using cisplatin and etoposide, is the reference treatment and frequently yields OR rates >50%. However, despite being chemosensitive, disease control is limited (8–10 months). Overall, advances in therapeutic chemotherapeutic options are required in the management of all types of advanced GEP endocrine tumours and evaluation of new drugs (e.g. irinotecan) and combination strategies (chemotherapy with local ablative therapies) are required in the future.

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Phase II study of continuous infusion fluorouracil and interferon alfa-2b in the palliation of malignant neuroendocrine tumors.

Cited by 40 publications

References 16 publications

Topotecan in Patients With Advanced Neuroendocrine Tumors

Topotecan in Patients With Advanced Neuroendocrine Tumors

GEP–NETs UPDATE: Biotherapy for neuroendocrine tumours

Chemotherapy for Gastro-Enteropancreatic Endocrine Tumours

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