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      Reversible sarcopenia in patients with gastrointestinal stromal tumor treated with imatinib

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          Abstract

          Background

          Imatinib is a long-term, oral, targeted therapy for high-risk resected and advanced gastrointestinal stromal tumours (GIST). It is known that sarcopenia affects prognosis and treatment tolerance in patients with various solid cancers. We analysed lumbar skeletal muscle index changes in imatinib-treated GIST patients. Imatinib tolerance was also assessed to evaluate the influence of pre-treatment sarcopenia.

          Methods

          Thirty-one patients with advanced ( n = 16) or high-risk resected ( n = 15) GIST treated with imatinib (400 mg/day) were analysed retrospectively. Lumbar skeletal muscle indexes were evaluated on computed tomography images obtained before starting imatinib for all patients and at 6 months for those initially sarcopenic. Sarcopenia was defined using consensual cutoffs. Imatinib-induced toxicities were assessed after 3 months of administration.

          Results

          Twelve (38.7%) of the 31 patients were sarcopenic, including one unassessable at 6 months. Seven (63.6%) of the 11 assessable sarcopenic patients became non-sarcopenic after 6 months of imatinib. Pre-treatment sarcopenia was not associated with grades 3–4 toxicities, but the mean number of all-grade toxicities per sarcopenic patient was significantly higher for those non-sarcopenic (4.1 vs. 1.7, respectively, p < 0.01) after 3 months of treatment. Grades 1–2 anaemia and grades 1–2 fatigue were more frequent for sarcopenic than non-sarcopenic patients (83% vs. 26%, P < 0.01 and 42% vs. 5%, P = 0.02, respectively).

          Conclusions

          Sarcopenia is reversible in some GIST patients treated with imatinib. Pre-imatinib sarcopenia is predictive of non-severe toxicities, particularly anaemia and fatigue.

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          Most cited references23

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          Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial.

          Imatinib is approved worldwide for use in gastrointestinal stromal tumours (GIST). We aimed to assess dose dependency of response and progression-free survival with imatinib for metastatic GIST. 946 patients were randomly allocated imatinib 400 mg either once or twice a day. Those assigned the once a day regimen who had progression were offered the option of crossover. The primary endpoint was progression-free survival. Analysis was by intention to treat. At median follow-up of 760 days (IQR 644-859), 263 (56%) of 473 patients allocated imatinib once a day had progressed compared with 235 (50%) of 473 who were assigned treatment twice a day (estimated hazard ratio 0.82 [95% CI 0.69-0.98]; p=0.026). Side-effects arose in 465/470 (99%) patients allocated the once daily regimen compared with 468/472 (99%) assigned treatment twice a day. By comparison with the group treated once a day, more dose reductions (77 [16%] vs 282 [60%]) and treatment interruptions (189 [40%] vs 302 [64%]) were recorded in patients allocated the twice daily regimen, but treatment in both arms was fairly well tolerated. 52 (5%) patients achieved a complete response, 442 (47%) a partial response, and 300 (32%) stable disease, with no difference between groups. Median time to best response was 107 days (IQR 58-172). If response induction is the only aim of treatment, a daily dose of 400 mg of imatinib is sufficient; however, a dose of 400 mg twice a day achieves significantly longer progression-free survival.
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            Sarcopenia in patients with bladder cancer undergoing radical cystectomy: impact on cancer-specific and all-cause mortality.

            The authors evaluated sarcopenia as a predictor of cancer-specific survival (CSS) and overall survival (OS) among patients with urothelial cancer of the bladder undergoing radical cystectomy (RC).
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              Sarcopenia Predicts Early Dose-Limiting Toxicities and Pharmacokinetics of Sorafenib in Patients with Hepatocellular Carcinoma

              Background Sorafenib induces frequent dose limiting toxicities (DLT) in patients with advanced hepatocellular carcinoma (HCC). Sarcopenia has been associated with poor performance status and shortened survival in cancer patients. Patients and Methods The characteristics of Child Pugh A cirrhotic patients with HCC receiving sorafenib in our institution were retrospectively analyzed. Sorafenib plasma concentrations were determined at each visit. Toxicities were recorded during the first month of treatment, and sarcopenia was determined from baseline CT-scans. Results Forty patients (30 males) were included. Eleven (27.5%) were sarcopenic. Eighteen patients (45%) experienced a DLT during the first month of treatment. Sarcopenic patients experienced significantly more DLTs than non-sarcopenic patients did (82% versus 31%, p = 0.005). Grade 3 diarrhea was significantly more frequent in sarcopenic patients than in non-sarcopenic patients (45.5% versus 6.9%, p = 0.01), but not grade 3 hand foot syndrome reaction (9% versus 17.2%, p = 1). On day 28, median sorafenib AUC (n = 17) was significantly higher in sarcopenic patients (102.4 mg/l.h versus 53.7 mg/l.h, p = 0.013). Conclusions Among cirrhotic Child Pugh A patients with advanced HCC, sarcopenia predicts sorafenib exposure and the occurrence of DLT within the first month of treatment.
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                Author and article information

                Journal
                J Cachexia Sarcopenia Muscle
                J Cachexia Sarcopenia Muscle
                jcsm
                Journal of Cachexia, Sarcopenia and Muscle
                John Wiley & Sons, Ltd (Chichester, UK )
                2190-5991
                2190-6009
                December 2015
                04 June 2015
                : 6
                : 4
                : 343-350
                Affiliations
                [1 ]Department of Gastro-Enterology and Digestive Oncology, CHU Reims, Hôpital Robert-Debré 51092, Reims, France
                [2 ]Department of Gastro-Enterology, Cochin Teaching Hospital, AP-HP, Université´ Paris Descartes Sorbonne Paris Cite, Paris, France
                [3 ]Clinical Research Unit, CHU Reims, Hôpital Robert-Debré 51092, Reims, France
                [4 ]Department of Radiology, CHU Reims, Hôpital Robert-Debré 51092, Reims, France
                Author notes
                *Correspondence to: Frédérick Moryoussef, Department of Gastro-Enterology and Digestive Oncology, CHU Reims, Hôpital Robert-Debré, Avenue du Général Koenig, 51092 Reims Cedex, France: Tel: +33 (0) 326787172; Fax: +33 (0) 326788836, Email: Fr.moryoussef@ 123456gmail.com
                Article
                10.1002/jcsm.12047
                4670743
                26673372
                21c9613b-3c01-40fd-b9fe-e783a221fa8c
                © 2015 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society of Sarcopenia, Cachexia and Wasting Disorders

                This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 26 September 2014
                : 13 April 2015
                : 23 April 2015
                Categories
                Original Articles

                Orthopedics
                imatinib,c-kit inhibitors,sarcopenia,gastrointestinal stromal tumours,toxicity,body composition

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