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      Capecitabine and Temozolomide in Patients with Advanced Pulmonary Carcinoid Tumours

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          Abstract

          Background: Temozolomide and capecitabine (CAPTEM) chemotherapy is known to be active in patients with pancreatic neuroendocrine tumours. Objective: This retrospective analysis set out to describe the efficacy and toxicity of CAPTEM in patients with advanced pulmonary carcinoids (PCs). Methods: Patients were included with advanced PC who had been treated with a maximum of 6 cycles of oral temozolomide 200 mg/m<sup>2</sup> on days 10–14 and capecitabine 750 mg/m<sup>2</sup> b.i.d. on days 1–14, repeated every 28 days, ­followed by monthly intramuscular injection of octreotide 30 mg long-acting release as maintenance treatment. Results: Of the 33 patients, all with well-differentiated PC, 61% had atypical carcinoid, 36% had Ki-67 index >10% and 42% had ≥3 organs involved by metastasis. CAPTEM was administered as first-line treatment in 42% of patients, and 17% had received prior somatostatin analogue treatment. Six patients (18%) achieved a partial response, 19 (58%) had stable disease and 8 (24%) developed progressive disease. After a median time of follow-up of 34.8 months, median progression-free survival (PFS) was 9.0 months and median overall survival 30.4 months. Median duration of disease response was 21.7 months and median duration of disease control 9.7 months. Patients with multi-organ metastasis had shorter PFS, but only when treated as second or third line with CAPTEM ( p = 0.023). Conclusions: CAPTEM induced a modest response and PFS rate, comparable to other studies with temozolomide in patients with advanced PC. The efficacy of CAPTEM should be compared to that of monotherapy with temozolomide in a prospective clinical trial.

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          Most cited references 23

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          First-line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas.

          Temozolomide is an active agent in metastatic pancreatic endocrine carcinomas. In vitro data indicate that the combination of capecitabine and temozolomide is synergistic for induction of apoptosis in neuroendocrine tumor cell lines. The authors retrospectively evaluated the efficacy of capecitabine and temozolomide in 30 patients with metastatic pancreatic endocrine carcinomas to assess response rate, progression free survival (PFS), and overall survival (OS). Patients with metastatic, well, or moderately differentiated pancreatic endocrine carcinomas who had not received prior systemic chemotherapy were treated with capecitabine (750 mg/m² twice daily, days 1-14) and temozolomide (200 mg/m² once daily, days 10-14) every 28 days. Among 30 patients treated, 21 (70%) patients achieved an objective radiographic response. Median progression-free survival was 18 months. The rate of survival at two years was 92%. Only 4 patients (12%) experienced grade 3 or 4 adverse events. The combination of capecitabine and temozolomide is associated with an exceptionally high and durable response rate in metastatic endocrine carcinomas of the pancreas. Clinical endpoints, including response rate, survival, and toxicity, are superior to those observed with streptozocin-based regimens. Copyright © 2010 American Cancer Society.
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            Pulmonary neuroendocrine (carcinoid) tumors: European Neuroendocrine Tumor Society expert consensus and recommendations for best practice for typical and atypical pulmonary carcinoids.

            Pulmonary carcinoids (PCs) are rare tumors. As there is a paucity of randomized studies, this expert consensus document represents an initiative by the European Neuroendocrine Tumor Society to provide guidance on their management.
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              Long-Term Efficacy, Survival, and Safety of [177Lu-DOTA0,Tyr3]octreotate in Patients with Gastroenteropancreatic and Bronchial Neuroendocrine Tumors.

              Purpose: Bronchial and gastroenteropancreatic neuroendocrine tumors (NET) are slow-growing tumors, which frequently express somatostatin receptors on their cell membranes. These receptors are targets for therapy with Lutetium-177-labeled somatostatin analogues. We have treated over 1,200 patients with peptide receptor radionuclide therapy (PRRT) with [177Lu-DOTA0,Tyr3]octreotate (177Lu-DOTATATE) since the year 2000 and present the results on efficacy, survival, and toxicity of this therapy.Experimental Design:For safety analysis, 610 patients treated with a cumulative dose of at least 100 mCi (3.7 GBq)177Lu-DOTATATE were included. A subgroup of 443 Dutch patients who were treated with a cumulative dose of at least 600 mCi (22.2 GBq)177Lu-DOTATATE before 2013 was further analyzed for efficacy and survival.Results:The objective response rate of the total group of patients was 39%. Stable disease was reached in 43% of patients. Progression-free survival (PFS) and overall survival (OS) for all NET patients were 29 months [95% confidence interval (CI), 26-33 months] and 63 months (95% CI, 55-72 months). Long-term toxicity included acute leukemia in four patients (0.7%) and myelodysplastic syndrome in nine patients (1.5%). No therapy-related long-term renal or hepatic failure occurred.Conclusions:PRRT with177Lu-DOTATATE is a favorable therapeutic option in patients with metastatic bronchial and gastroenteropancreatic NETs that express somatostatin receptors. PRRT with177Lu-DOTATATE is safe with few side-effects and shows good response rates with PFS of 29 months and OS of 63 months.Clin Cancer Res; 23(16); 4617-24. ©2017 AACR.
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                Author and article information

                Journal
                NEN
                Neuroendocrinology
                10.1159/issn.0028-3835
                Neuroendocrinology
                S. Karger AG
                0028-3835
                1423-0194
                2020
                April 2020
                23 August 2019
                : 110
                : 5
                : 413-421
                Affiliations
                aDepartment of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom
                bCellular Pathology, Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom
                cUniversity of Manchester, Manchester, United Kingdom
                Author notes
                *Wasat Mansoor, MBChB, FRCP, PhD, Department of Medical Oncology, The Christie NHS FoundationTrust, 550 Wilmslow Road, Manchester M20 4BX (UK), E-Mail Was.Mansoor@christie.nhs.uk
                Article
                502864 Neuroendocrinology 2020;110:413–421
                10.1159/000502864
                31437838
                © 2019 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 4, Tables: 4, Pages: 9
                Categories
                Research Article

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