Normal protein anabolic response to hyperaminoacidemia in insulin-resistant patients with lung cancer cachexia

Winter, Aaron; MacAdams, Jacqueline; Chevalier, Stéphanie

doi:10.1016/j.clnu.2012.05.003

Cited by 112 publications

(108 citation statements)

References 53 publications

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“…An interesting next step will be to investigate whether interventions, such as nutritional and exercise interventions, which have the potential to counteract the SMM loss during intensive treatment and support potential gain during less intensive treatment, also result in improved outcome of treatment. A gain in SMM has recently be shown in nutritional intervention studies in which protein and/or omega 3 fatty acids enriched high energy were added to the diet of non‐small cell lung carcinoma patients,26, 27, 28 and in an exercise intervention study performed during chemotherapy for breast cancer, a significant increase of muscle strength was observed in the intervention group 29. Especially, a multimodal approach in which nutrition and exercise are combined might provide a promising future strategy to prevent SMM loss and subsequent reduced treatment outcomes 30…”

Section: Discussionmentioning

confidence: 99%

Impact of different palliative systemic treatments on skeletal muscle mass in metastatic colorectal cancer patients

Kurk

Peeters

Dorresteijn

et al. 2018

J cachexia sarcopenia muscle

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BackgroundObservational studies suggest that loss of skeletal muscle mass (SMM) is associated with chemotherapy‐related toxicity, poor quality of life, and poor survival in metastatic colorectal cancer (mCRC) patients. Little is known about the evolution of SMM during palliative systemic therapy. We investigated changes in SMM during various consecutive palliative systemic treatment regimens using repeated abdominal computed tomography scans of mCRC patients who participated in the randomized phase 3 CAIRO3 study.MethodsIn the CAIRO3 study, mCRC patients with stable disease or better after 6 cycles of first‐line treatment with capecitabine + oxaliplatin + bevacizumab (CAPOX‐B) were randomized between maintenance treatment with capecitabine + bevacizumab (CAP‐B) or observation. Upon first disease progression, in both groups, CAPOX‐B or other treatment was reintroduced until the second disease progression, which was the primary study endpoint. We analysed 1355 computed tomography scans of 450 (81%) CAIRO3 patients (64 ± 9.0 years, CAP‐B n = 223; observation n = 227) for SMM at four time points (i.e. prior to the start of pre‐randomization initial treatment, at randomization, and at first and at second disease progression) using the Slice‐o‐matic software and single slice evaluation at the lumbar 3 level. By using accepted and widely used formulas, whole body SMM was calculated. A linear mixed effects model, adjusted for relevant confounders, was used to assess SMM changes for the total group and within and between study arms.ResultsDuring 6 cycles of initial treatment with CAPOX‐B prior to randomization, SMM decreased significantly in all patients [CAP‐B arm: −0.53 kg (95% CI −1.12; −0.07) and observation arm: −0.85 kg (−1.45; −0.25)]. After randomization, SMM recovered during CAP‐B treatment by 1.32 kg (0.73; 1.90) and observation by 1.20 kg (0.63; 1.78) (median time from randomization to first disease progression 8.6 and 4.1 months for CAP‐B arm and observation arm, respectively). After first progression and during reintroduction treatment with CAPOX‐B or other treatment, SMM again decreased significantly and comparable in both arms, CAP‐B: −2.71 kg (−3.37; −2.03), and observation: −2.01 kg (−2.64; −1.41) (median time from first progression until second progression CAP‐B arm: 4.7 months and observation arm: 6.6 months).ConclusionsThis longitudinal study provides a unique insight in SMM changes in mCRC patients during palliative systemic treatment regimens, including observation. Our data show that muscle loss is reversible and may be influenced by the intensity of systemic regimens. Although studies have shown prognostic capacity for SMM, the effects of subsequent changes in SMM are unknown and may be clues for new future therapeutic interventions.

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Section: Discussionmentioning

confidence: 99%

Impact of different palliative systemic treatments on skeletal muscle mass in metastatic colorectal cancer patients

Kurk

Peeters

Dorresteijn

et al. 2018

J cachexia sarcopenia muscle

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“…Contrary to popular belief, sarcopenia in cancer is reversible even in people of older age, deconditioning, inflammation and concurrent comorbid conditions (62) . Evidence also shows that anabolic responsiveness is not suppressed by nutrition interventions (63)(64)(65)(66)(67)(68) . In spite of this evidence, recent pharmacological studies on retention or gain of muscle mass in cancer have failed to provide (or account for) sufficient energy and protein to sustain muscle mass accretion (63,65) .…”

Section: The Impact Of Abnormal Body Composition On Nutritional Therapymentioning

confidence: 99%

Sarcopenia and cachexia in the era of obesity: clinical and nutritional impact

et al. 2016

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Our understanding of body composition (BC) variability in contemporary populations has significantly increased with the use of imaging techniques. Abnormal BC such as sarcopenia (low muscle mass) and obesity (excess adipose tissue) are predictors of poorer prognosis in a variety of conditions or clinical situations. As a catabolic illness, a defining feature of cancer is muscle loss. Although the conceptual model of wasting in cancer is typically conceived as involuntary weight loss leading to low body weight, recent studies have shown that both sarcopenia and cachexia can be present with obesity. The combination of low muscle and high adipose tissue (sarcopenic obesity) is an emerging abnormal BC phenotype prevalent across the body weight, and hence BMI spectra. Sarcopenia and sarcopenic obesity in cancer are in most instances occult conditions, which have been independently associated with higher incidence of chemotherapy toxicity, shorter time to tumour progression, poorer outcomes of surgery, physical impairment and shorter survival. Although the mechanisms are yet to be fully understood, the associations with poorer clinical outcomes emphasise the value of nutritional assessment as well as the need to develop appropriate interventions to countermeasure abnormal BC. Sarcopenia and sarcopenic obesity create diverse nutritional requirements, highlighting the compelling need for a more comprehensive and differentiated understanding of energy and protein requirements in this heterogeneous population.

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“…These effects were paralleled by a decrease in Atrogin1 and MuRF1 expression (Asp et al 2010). Interestingly, emerging evidence has indicated that insulin resistance-mediated blunted protein anabolism is not refractory to post-prandial physiological amino-acid infusion, indicating conventional nutritional support to be a promising approach for overcoming anabolic resistance (Winter et al 2012). As such, insulin sensitizers are good candidates for the therapeutic treatment of cancer cachexia, but clinical studies to confirm experimental data are necessary.…”

Section: New Perspectives For the Treatment Of Cancer Cachexiamentioning

confidence: 99%

“…Cancer cachexia promotes insulin resistance, which not only blunts muscle glucose uptake and liver glucose production, but also inhibits protein anabolism, contributing to muscle atrophy (Yoshikawa et al 2001, Winter et al 2012. Metformin, the most widely used agent for the treatment of type 2 diabetes, increases food intake and prolongs survival in cachectic rats bearing Walker256 tumors (Ropelle et al 2007).…”

Section: New Perspectives For the Treatment Of Cancer Cachexiamentioning

confidence: 99%

Molecular and neuroendocrine mechanisms of cancer cachexia

Mendes

Pimentel

Costa

et al. 2015

Journal of Endocrinology

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Cancer and its morbidities, such as cancer cachexia, constitute a major public health problem. Although cancer cachexia has afflicted humanity for centuries, its underlying multifactorial and complex physiopathology has hindered the understanding of its mechanism. During the last few decades we have witnessed a dramatic increase in the understanding of cancer cachexia pathophysiology. Anorexia and muscle and adipose tissue wasting are the main features of cancer cachexia. These apparently independent symptoms have humoral factors secreted by the tumor as a common cause. Importantly, the hypothalamus has emerged as an organ that senses the peripheral signals emanating from the tumoral environment, and not only elicits anorexia but also contributes to the development of muscle and adipose tissue loss. Herein, we review the roles of factors secreted by the tumor and its effects on the hypothalamus, muscle and adipose tissue, as well as highlighting the key targets that are being exploited for cancer cachexia treatment.

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Normal protein anabolic response to hyperaminoacidemia in insulin-resistant patients with lung cancer cachexia

Cited by 112 publications

References 53 publications

Impact of different palliative systemic treatments on skeletal muscle mass in metastatic colorectal cancer patients

Impact of different palliative systemic treatments on skeletal muscle mass in metastatic colorectal cancer patients

Sarcopenia and cachexia in the era of obesity: clinical and nutritional impact

Molecular and neuroendocrine mechanisms of cancer cachexia

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