Sarcopenia associated with chemotherapy and targeted agents for cancer therapy
Review Article

Sarcopenia associated with chemotherapy and targeted agents for cancer therapy

Mellar P. Davis1, Rajiv Panikkar2

1Department of Palliative Care, 2Cancer Center, Geisinger Medical Center, Danville, PA, USA

Contributions: (I) Conception and design: M Davis; (II) Administrative support: R Panikkar; (III) Provision of study materials or patients: M Davis; (IV) Collection and assembly of data: All authors; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Mellar P. Davis, MD, FCCP, FAAHPM. Department of Palliative Care, Geisinger Medical Center, 100 N Academy Ave., Danville, PA, USA. Email:

Abstract: Clinicians often believe that cachexia is caused by cancer and anorexia as a toxicity of chemotherapy or targeted anti-cancer agents. It is now recognized that chemotherapy and certain targeted agents cause sarcopenia which reduce physical function and quality of life. Pre-treatment sarcopenia predicts chemotherapy toxicity, reduced response, increased disability, poor anti-tumor response and survival. Though bioelectrical impedance and dual energy X-ray absorptiometry (DEXA) scans have been used in the past for body composition measurements, CT scan cuts at the level of the 3rd lumbar vertebral body with measurement of skeletal muscle and visceral and subcutaneous fat areas has become standard. Nonpharmacological approaches to reducing sarcopenia during chemotherapy includes resistance training and dietary counselling. Pharmacologic therapies include vitamin D replacement if depleted, omega-3 fatty acids, testosterone and selective androgen receptor modulators (SARMS) and ghrelin. A comprehensive multimodal and multiple drug approach is likely to be better than single modalities. However, this is yet to be proven. Finally, it is not known if intervening to prevent or reverse sarcopenia will have a clinical benefit in terms of better tolerance to cancer therapy, physical function, well-being, tumor response and survival. Reversing sarcopenia and improving objective outcomes should be the goal of therapy.

Keywords: Sarcopenia; chemotherapy; prognosis; response; treatment

Submitted Jun 29, 2018. Accepted for publication Aug 02, 2018.

doi: 10.21037/apm.2018.08.02


Weight is a common metric when evaluating a patient’s health. Cachexia by definition involves involuntary weight loss. Body mass index (BMI) is weight adjusted for stature (kg/m2), is used often for health assessment and nutritional status. Body surface area has been used to measure metabolic mass for chemotherapy administration (1). However, weight and weight per stature does not accurately assess body composition. The proportion of lean body mass (LBM), skeletal muscle and visceral fat as well as subcutaneous fat vary significantly between individuals with the same BMI. The increase in obesity within society may lead clinicians to misjudge the health of patients and grossly overestimate skeletal muscle mass. The appearance of classical cachexia has become much less apparent today. Patients may have critical skeletal muscle loss to a much greater extent than fat and remain overweight. Patients do not necessarily proportionally gain or lose fat and muscle at equal rates with a change in weight (2-4). This is also true for patients with cancer who may have widely varying skeletal muscle mass and fat mass as well as distribution of fat per weight which has a profound effect on tolerance to anti-tumor therapy, efficacy, drug limiting toxicities (DLT), progression free, and overall survival (5-10).

Definition and measurement of sarcopenia

There are distinct differences when measuring sarcopenia in the elderly population and in cancer patients. The geriatrician focuses on function and disability, while the oncologist measures muscle mass and weight compared to a population standard. A recent sarcopenia definition in the geriatric literature is “a loss of muscle associated with loss of function” (11). Elderly individuals are screened by gait speed, the rate at which they can sit and stand several times or by hand grip strength or by a series of tests. Falling below population standards predicts frailty and mortality (12,13). However, there is a complex relationship between muscle mass, muscle loss and reduced function which is not linear. Muscle mass diminishes 0.5–1% per year beginning around the age of 40 which accelerates after the age of 65. Muscle strength diminishes 3–4% per year in men and 2.5–3% per year for women around the age of 75 (14-16).

Pre-sarcopenia can be defined as low muscle mass without loss of strength or physical disability or performance. Sarcopenia is defined as low muscle mass with either reduced muscle strength or reduced physical performance relative to population standards. Severe sarcopenia is defined as low muscle mass, reduced muscle strength and reduced physical performance relative to population standards. Dynapenia is age-associated loss of muscle strength not caused by neurologic or muscle diseases (17).

Oncologists and investigators interested in sarcopenia associated with cancer have largely used anatomical measurements of skeletal muscle mass as the initial screen. This is done through the use of bioelectrical impedance, dual energy X-ray absorptiometry (DEXA), and CT scan by the composition at a single cut through the level of the L3 vertebral body (18-26). Bioelectrical impedance measures tissue resistance and capacitance but body composition is computed by equations derived from normal populations which are certainly less accurate than by direct measurement through CT scans. However, the phase angle which is a relationship of capacitance to resistance directly reflects muscle mass and cellular health (27,28). The advantages to bioelectrical impedance is that it is inexpensive, portable, can be repeated frequently and does not expose patients to radiation. DEXA scans measure appendicular muscle but are cumbersome and expose patients to radiation. Patients undergoing chemotherapy or targeted therapy are often restaged after a few cycles of therapy or periodically. The images can be used to measure tumor response, skeletal muscle mass, as well as visceral and subcutaneous fat mass.

CT scan body composition uses Hounsfield units (−29 to 150) to measure skeletal muscle area at a single L3 cross sectional area (4). The L3 vertebral CT scan image includes 7 muscles; psoas, erector spinae, quadratus lumborum, transversus abdominis, external obliques, internal obliques, and rectus abdominis. Some studies used the cross section of the psoas alone (29). Abdominal and subcutaneous fat mass area can be quantified. Gender specific norms have been established. For males normal muscle mass is greater than or equal to 52.4 cm2/m2 and for females 38.5 cm2/m2. This has been correlated with whole body skeletal muscle mass and externally validated using mortality (4,7,30). There are several software programs that used to perform these measurements; MIMICS TM (Materialise HQ, Leuven, Belgium), SliceOmatic TM (Tomovision, Magog, CA), NIH IMAGEJ TM (http://IMAGEJgov/ij).

Causes of sarcopenia during chemotherapy and targeted therapy

There are four main causes of sarcopenia during chemotherapy; (I) impaired food intake with reduction in vitamin D; (II) omega 3 fatty acids and protein; (III) reduced physical activity secondary to fatigue; (IV) a direct effect of chemotherapy or targeted agents on muscle; (V) malabsorption secondary to mucositis or treatment related pancreatic insufficiency (31).

Cisplatin, irinotecan, doxorubicin, and etoposide cause direct muscle loss through activation of the transcription factor NF kappa B which upregulates ubiquitin and proteasomes, increases proteolysis and inflammatory cytokines (IL-1beta,IL6 and TNF alpha) which increases E3 ligases (atrogin-1) and increases ubiquitin protein binding for proteolysis (32). TNF alpha accelerates catabolism (protein loss, insulin resistance), muscle contractile dysfunction, and disrupts myogenesis leading to muscle weakness (33-35). Cisplatin downregulates protein kinase B (AKT)/mammalian target of rapamycin (mTOR)/leading to loss of myogenesis (36). Chemotherapy induces oxidative stress and increases reactive oxygen species (ROS) in muscle (36,37). Tumor growth factor (TGF) beta proteins are increased with chemotherapy which upregulates myostatin altering the balance of muscle metabolism toward catabolism (36,38,39). Combination chemotherapy causes mitochondrial damage which reduces cytochrome C needed for oxidative phosphorylation and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alpha), a protein transcriptional coactivator that regulates energy metabolism, mitochondrion biogenesis and muscle fiber type (40). Muscle wasting is associated with up-regulation of ERK1/2 and p38 MAPKs which impairs the AKT/mTor pathway leading to muscle atrophy (40). Chemotherapy causes reduction in muscle microvasculature through antiangiogenesis (41).

On the other hand, chemotherapy may counter cancer induced sarcopenia by reducing tumor burden. In a mouse model, 5FU reduced protein turnover by reducing one of the E3 ligases (atrogen-1) which would impair proteasome proteolysis. 5FU also increased muscle ribosomal activity and muscle metabolic capacity by increasing PGC-1alpha. Muscle autophagy is also reduced (42).

Outcomes associated with sarcopenia and sarcopenia obesity during cancer therapy

In a retrospective study of patients receiving neoadjuvant chemotherapy (NAC) for urothelial cancer, 14% had sarcopenia at the beginning of treatment as measured by CT scan body composition and 20% by bioelectrical impedance. There was no correlation between the presence of sarcopenia and a prognostic nutritional index using albumin and lymphocyte blood levels. After 3 cycles of NAC, skeletal mass decreased while fat mass increased suggesting that cisplatin NAC causes sarcopenic obesity (42).

Several studies of foregut origin malignancies found a pre-treatment sarcopenia prevalence of 26–47% which increased after chemotherapy. Pre-NAC sarcopenia and the development of sarcopenia during chemotherapy correlated with an increased risk for neutropenic fever, a greater degree of dose-limiting toxicity (DLT), reduced successful surgical resections, and a shorter survival (43-45). A large study (n=225) of patients receiving NAC or palliative systemic chemotherapy also demonstrated a high prevalence of sarcopenia (40%) prior to treatment. In addition, close to half of patients had myosteatosis and 62% had cancer cachexia (involuntary weight loss of 5% or more over 6 months). Those on NAC lost 6.6 cm2 of skeletal muscle by CT scan body composition. Those on palliative chemotherapy lost on average 3.9% of the skeletal muscle mass by 100 days. Reduced muscle mass of >6% predicted reduced survival with a hazard ratio (HR) of 2.7 (46). In this study a high number of nutritionally vulnerable patients, with demonstrated abnormal body composition on CT analysis were misclassified by nutritional indices. The authors cautioned when categorizing the nutritional risk of oncology patients using nutritional tools only (47).

Two studies involving the elderly undergoing chemotherapy have conflicting findings. A smaller study (n=103) involved patients with a mean age of 70. The authors found that hand grip strength predicted survival whereas CT scan body composition including the measurement of myosteatosis did not predict for drug toxicity or survival (48). An earlier study involved patients (n=131 with a median age of 72 years). Pre-sarcopenia was present in 48%, sarcopenia in 18.5% and severe sarcopenia in 7.7%. Severe sarcopenia was associated with loss of physical independence after chemotherapy with a HR of 5.95. Skeletal muscle mass in this study correlated with strength but not tests of physical function (49).

In a study which sequentially measured skeletal muscle mass through repeated CT scans during palliative chemotherapy for lung cancer, the mean reduction in skeletal muscle mass over time was 1.4 kg. Most who had objective response to chemotherapy had stable to improved muscle mass. Maintaining or gaining muscle mass predicted survival (10.7 vs. 5.8 months) (50). A second study in a similar group of patients used the phase angle as a measure of skeletal muscle mass. A phase angle less than 5.8 predicted a poor survival (HR 3.0) by multivariable analysis (18).

Even in patients undergoing a curative therapy, sarcopenia had clinical significance. In a group of patients undergoing curative treatment for large B-cell lymphomas, sarcopenia predicted a poorer 2-year survival (46% vs. 86%) with a HR of 3.22 for mortality (51). Patient who have pre-treatment sarcopenia undergoing curative resection for colorectal cancer have a shorter recurrence free survival and overall survival with a HR of 2.18 and 2.27 respectively (52). Post-surgical anastomotic leak occurred more frequently in sarcopenic patients (53).

These are only a few of the studies which have demonstrated the adverse effects of sarcopenia on the course of cancer. Sarcopenia predicts reduced survival in multiple cancers. Not only does sarcopenia predict reduced overall survival, but also increases a number of risks including postoperative infections, the need for inpatient rehabilitation, recurrent hospitalizations, hospital length of stay (54-58), respiratory and surgical complications, intensive care unit admissions, and days of enteral nutrition because of delays in gastric emptying (53,59-75).


Excessive levels of inter- and intra-muscular adipose tissue and intramyocellular lipids adversely impacts metabolism and force generation with clinically relevant outcomes (76,77). Myosteatosis increases with aging, regardless of changes in body weight, which is more prevalent in diabetics and reflects insulin resistance, impaired secretion of adipokines and altered skeletal muscle blood flow (78,79). Myosteatosis of thigh muscles as measured by reduced Hounsfield units, is associated with an increased risk of hip fracture in the elderly and with reduced muscle strength, physical performance, and muscle mass (80). As discussed later, muscle depletion is associated with low plasma eicosapentaenoic (EPA) and docosahexaenoic (DHA) in cancer and supplementation with omega-3 fatty acids has been shown to ameliorate muscle loss and myosteatosis in clinical studies (81). In multiple studies, low attenuation of muscle on CT scans has been associated with reduced cancer survival with a HR of 1.36 to 2.5 (8,77,82-86).

Sarcopenic obesity

As mentioned previously, cisplatin has been associated with sarcopenic obesity. In a series of patients with lung cancer undergoing chemotherapy, after 4 months of chemotherapy, patients exhibited sarcopenia with decreased muscle and increased visceral adiposity relative to subcutaneous fat mass. This was not adequately mirrored by BMI and weight loss (87). In addition, cyclophosphamide, doxorubicin, vincristine and prednisone, used to treat non-Hodgkin’s lymphoma, has been associated with increased fat mass with stable LBM. Weight gain during chemotherapy, with an unfavorable change in body composition, misleads treating physicians to attribute weight gain as a sign of regaining health (88).

Sarcopenic obesity has an independent adverse effect on clinical outcomes. In a retrospective study of patients with pancreatic cancer, overall and recurrence-free survival rates in patients with a high visceral to subcutaneous fat ratio were significantly lower than those in patients with low ratio. Survival and relapse free survival rates of patients with sarcopenic visceral obesity were significantly lower compared with those without sarcopenic obesity. The ratio of visceral to subcutaneous fat was an independent risk factor for mortality with a HR of 1.58 suggesting that visceral fat mass plays a role in clinical outcomes (89). In a series of patients with pancreatic cancer, 18 had sarcopenic obesity, 44 had obesity without sarcopenia and 62 had sarcopenia alone. Obese sarcopenia was an independent risk predictor for mortality with a HR of 2.07. Multiple additional studies have demonstrated adverse cancer-related outcomes for those with sarcopenic obesity (1,6,7,42,90-98).

One question that arises when reviewing these studies is how much the increase in fat mass plays a role in predicting adverse outcomes relative to sarcopenia alone. A second question is whether it is the overall increase in fat mass or its relative distribution between subcutaneous versus visceral compartments (in addition to reduced skeletal muscle mass) that is the important clinical feature that defines sarcopenic obesity. It has been suggested that chemotherapy dosing paradigms should differ between the obese without sarcopenia and the sarcopenic obese. Chemotherapy doses perhaps should be limited to a 2 m2 BSA in the sarcopenic obese due to the increased risk for chemotherapy related toxicity (1).

Sarcopenia and targeted therapies

Certain targeted agents are associated with sarcopenia and the cancer outcomes of targeted therapy can be influenced by sarcopenia. The comparison was made between chemotherapy and targeted agents as to the prevalence of sarcopenia on therapy. Most patients were on epidermal growth factor receptor tyrosine kinase inhibitors. Sarcopenia was measured by CT scan body composition. Chemotherapy produced greater muscle loss relative to targeted agents. There was also greater variation in skeletal muscle loss or gains with chemotherapy. The authors attributed this to less anorexia with targeted agents as well as differences in toxicity (99).

Three classes of targeted agents have been shown to improve skeletal muscle mass: poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors and the mitogen-activated protein (MEK) inhibitor, selumetinib. PARP activation causes muscle mass loss and muscle dysfunction in animal models (100,101). Inhibitors of PARP reduce muscle oxidative stress, reduces muscle catabolism, enhances muscle metabolism and improves mitochondrion function and biogenesis (100,102-106). PARP inhibitors improve exercise capacity by boosting mitochondrion respiratory capacity in mice (103).

Selumetinib was studied in BALB/C mice implanted with C26 adenocarcinoma. Selumetinib reduced E3 ligases which are important to proteasome proteolysis. Selumetinib also enhanced the AKT/mTor pathway (107). Selumetinib increased muscle mass and weight in 80% of patients treated for biliary cancers and produced an objective response in 12% suggesting that the anabolic benefits are independent of anti-cancer activity (108,109).

Imatinib mesylate inhibits signaling from tyrosine kinase receptors, including PDGFR alpha, and has been used to treat CML. PDGFR alpha is expressed in muscle mesenchymal progenitors, when stimulated induces muscle fibrosis (110). Imatinib reverses the sarcopenia associated with gastrointestinal stromal tumors (GIST) (111).

There are targeted agents which have been either associated with sarcopenia or have outcomes are adversely influenced by sarcopenia. Sorafenib has the greatest evidence for inducing sarcopenia. Sorafenib activates the proteasome and calcium dependent proteolysis pathways (112). Sorafenib causes progressive loss of skeletal muscle mass over time, unrelated to cancer (113). On the other hand, pre-existing sarcopenia on sorafenib is associated with disease limiting toxicity (DLT) and a shortened survival (114-116). Sorafenib responses are diminished in individuals with sarcopenic obesity with increased visceral fat (117,118). However, there is a single study that suggests increased visceral fat in patients on endothelial growth factor-targeted therapy portends a better outlook and prognosis (119). Patients with sarcopenia have a significantly inferior progression free survival and overall survival compared to non-sarcopenic patients [PFS: 7.6 vs. 18.2 months (120)]. Sunitinib therapy in sarcopenic patients is associated with DLT with a 4-fold increased risk in grade 3 and vascular toxicities (121). Dose limiting toxicity is seen in half of patients at 6 months who are sarcopenic prior to starting sunitinib therapy. Those with sarcopenia and reduced fat mass have a 90% chance of experiencing DLT and an increased number of treatment related toxicities (5 vs. 2) (122).

Inhibitors of the mTor pathway have been associated with sarcopenia. The use of mTOR inhibitors significantly decreases skeletal muscle area and LBM but has no effect on adipose tissue or body weight (123). Skeletal muscle mass is an independent prognostic factor for patients with metastatic renal cell cancer treated with everolimus (21.9 vs. 10 months for those with the highest to lowest L3 muscle cross section area) (124).

Treatment of sarcopenia

Reversibility and multimodality therapy

Patients with cancer have anabolic capacity. Sarcopenia can be reversed in older aged individuals, those that are deconditioned, and in those with multiple comorbidities (125). Serial studies have demonstrated that muscle protein synthesis can be stimulated in these individuals (126,127). However, it is likely that reversibility will depend on multimodality approaches. Pharmacologic trials have frequently been carried out without regard to adequate nutrition intake within the trial design. Failure to reverse sarcopenia may not be related to failure to generate anabolism but inadequate calorie intake (128,129).


Patients with cancer are often catabolic and the need for protein intake may not be adequately predicted by their BMI. At least 35% of patients with cancer have inadequate protein intake (less than 1 g/kg body weight per day) (19). Protein intake should be 1.2–1.5 g/kg per day for those with acute or chronic diseases (130,131). Leucine rich supplements have been shown to maintain or build muscle mass (132,133). Leucine was found has beneficial effects on body weight, BMI, and LBM in older persons prone to sarcopenia, but does not improve muscle strength (134). Healthy elderly men can take in 500 mg/kg per day without an increase in ammonia. A more conservative approach would be an intake of 351 mg/kg per day (135).

Beta-hydroxy beta-methyl butyrate (HMB) supplements have been used to build muscle mass. HMB enhances sarcoplasmic reticulum thus improves to peak contraction force in vitro (136). HMB improves the proliferation of muscle stem cells in fast twitch muscles in mice which increases muscle mass (137). So it is rational to think that HMB might increase muscle mass and function. In a randomized trial involving individuals over the age of 65, HMB improved strength and muscle quality independent of resistance exercises (138). Seven randomized trials involving 287 patients found that patients gain muscle mass without improved function or strength (139). There is no study that the authors could find which addressed the use of HMB during chemotherapy. Studies are needed to address the specific effectiveness of HMB in attenuating muscle wasting in various muscle-wasting disorders (140).

Besides improving protein intake overall and the types of protein consumed, the amount of simple carbohydrates should be reduced with the emphasis on whole foods rather than processed foods and high fiber intake (141-143). One caveat though is that patients who develop dysgeusia on chemotherapy might not find protein palatable (144,145). Dronabinol reduces the chemosensory changes that occur on chemotherapy and allows patients to increase protein intake (146).

Vitamin D

We recommend checking vitamin D levels and replacing vitamin D if low which has a low risk and potential benefits (133,147). Prolonged deficiency is reported to produce both muscle loss and weakness (147-149). The muscle losses are particularly severe for type II muscle which are prevented by maintaining levels 25 hydroxyvitamin D >20 ng/mL (149,150). In addition, to low 25 hydroxyvitamin D, high parathyroid hormone levels (PTH) levels (≥4.0 pmol/L) are associated with an increased risk for sarcopenia (151). Replacement of vitamin-D increases muscle fiber size and lowers extremity proximal muscle strength (152,153). Vitamin D deficiency is defined as a 25 hydroxyvitamin D3 level of <20 ng/mL, insufficient when 21–29 ng/mL. The prevalence of vitamin D deficiency is 36–47% during the winter in the general population and is likely to be higher in patients with cancer who have insufficient intake and insufficient light exposure (154).

Vitamin D (1 alpha, 25 dihydroxyvitamin D3) binds to vitamin-D receptors (VDR) which are transported to the nucleus where they interact with 9-cis-retinoid acid receptors and form a heterodimer. The heterodimer modulates the FOXO subfamily which is responsible for myoblast maturation. The end result is downregulation of myostatin (155). Besides atrophy of type II muscle fibers, vitamin D deficiency is associated with myosteatosis and loss of satellite cells necessary for muscle regeneration (156-158).

Omega 3 fatty acids

Myosteatosis and sarcopenia have been associated with low plasma levels of omega-3 fatty acids (OMF). And conversely, supplementation of diets with OMF ameliorate sarcopenia and reverse myosteatosis in clinical studies (81,159).

OMF improves muscle mass by several different mechanisms. OMF increases mTor ribosomal activity through phosphorylation and inhibits mTOR translocation into lysosomes (160,161). Muscle anabolic responses to insulin and amino acid infusion are greater in the presence of OMF (162). Another mechanism involves increases in uncoupling protein-2 by mitochondrion which reduces reactive oxygen species and down-regulates proteasome proteolysis (163,164).

A series of small studies have been done where omega-3 fatty acid supplementation has been given during chemotherapy. A dose finding study found that 6 g of 0MF per day was the maximum tolerable dose. OMF improved appetite and fatigue. Participants in this study had advanced lung cancer and a systemic immune-metabolic syndrome (chronic systemic inflammatory syndrome) (165). A group of patients who were receiving palliative chemotherapy for visceral breast cancer metastases were randomized between the OMF docosahexaenoic acid (DHA) 1.8 g daily or placebo. Chemotherapy responses occurred in 88% of those on DHA versus 44% of those treated with anthracycline-based chemotherapy alone. Those with the highest plasma DHA levels had a significantly longer survival (34 vs. 18 months) and less chemotherapy toxicity (166). A trial of patients undergoing palliative chemotherapy for lung cancer (n=92) randomized patients (n=112) between the omega-3 fatty acid eicosapentaenoic acid (EPA) and an isocaloric diet. All patients received paclitaxel and cisplatin/carboplatin chemotherapy. EPA randomized patients followed a standardized menu and two containers (237 mL each) per day of ProSure® (Abbott Nutrition, Columbus, Ohio, USA). Calorie and protein consumption in the control group decreased during the two cycles of treatment (P=0.08 and P=0.04 respectively), while in the experimental group dietary intake of calories and protein were maintained. The EPA group had increased energy, protein, carbohydrate and fat intake when including oral supplement compared with control group. The EPA group had an increased global health status while the control group did not. LBM decreased in the control group but increased in the EPA group by the second cycle of chemotherapy. There were no differences in tumor response or survival (167).

In a small randomized trial (n=40), 2.2 g of EPA during chemotherapy for lung cancer resulted in less muscle and weight loss and less myosteatosis than patients who were not supplemented (168). Sixty-nine percent of patients in the EPA group gained or maintained muscle mass while only 29% of patients in the control group did. Fat mass was unchanged between groups. A second study by the same group found that 2.5 gms of EPA daily improved response rate and clinical benefit of chemotherapy for lung cancer. Eighty percent of those on EPA had a clinical benefit to chemotherapy versus 42% of those in the control group. The trial was small with only 46 patients and thus was under powered. Survival at 1 year was 60% for those receiving the supplement versus 39% of those on standard care though this was not significantly different (P=0.15) (159).

There are multiple randomized trials demonstrating benefits to EPA and DHA supplementation during chemotherapy but trial populations were small and most were phase II designs. Large randomized trials will be needed to confirm these promising findings.


Men with cancer often have low testosterone levels which could lead to sarcopenia. Women may benefit from testosterone during chemotherapy in attempts to maintain muscle mass. A small randomized trial (n=24) of patients with cervical and head and neck cancer used testosterone enanthate 100 mg weekly for 7 weeks during therapy. Appendicular skeletal muscle mass was maintained and body weight increased on average by 1.3 kg. Quality of life improved but physical well-being, strength and performance were not improved (169).

Selective androgen receptor modulators (SARMS)

Androgens promote growth hormone release, stimulate appetite, increase LBM and regulate energy homeostasis but also increase the risk for cardiovascular disease, depression, aggression and sleep disordered breathing (170). SARMS have been developed to take advantage of the anabolic effects of androgen receptor agonists while avoiding the adverse effects of androgen on prostate, heart, and liver (171,172). Selectivity occurs through different interactions with the androgen receptor leading to distinctly different receptor conformation, and interactions with coactivators and corepressors resulting in differences in recruitment of nongenomic signaling and gene regulation (173,174). SARMS have been used in both genders to improve bone health and increase LBM, countering osteoporosis, sarcopenia and cachexia (175,176).

Enobosarm is a hyper-myo-anabolic SARM with high oral bioavailability and preclinical safety. It is not subject to peripheral aromatase or 5-alpha reductase metabolism and thus is not converted to an estrogenic or androgenic metabolite (177). In a phase 2 study patients with cancer who were treated with enobosarm had improvement in LBM and stair climbing power. There was no reduction in free testosterone levels (129). However, two phase III trials involving patients receiving chemotherapy for lung cancer found that enobosarm improved LBM but failed to improve stair climbing power which was a co-primary outcome of the study (178,179).


Ghrelin is a growth hormone secretagogue receptor agonist which increases appetite by up-regulating neuropeptide Y and agouti-related protein in the hypothalamus (180). Ghrelin also has skeletal muscle anabolic effects even though muscle lacks growth hormone secretagogue receptors (36). Experimentally ghrelin reverses the adverse effects of cisplatin and cancer on skeletal muscle. Cisplatin and tumor down-regulate the AKT pathway, MyoD and myogenin while up-regulating E3 ligases responsible for proteasome proteolysis. In addition, cisplatin up-regulates myostatin. Ghrelin reverses this (36). In animals, cisplatin causes muscle necrosis with associated inflammatory cell infiltrates which is prevented by ghrelin. In animals ghrelin not only prevents sarcopenia but improves muscle strength (181).

Anamorelin, a growth hormone secretagogue receptor agonist, has been used in several chemotherapy trials to decrease sarcopenia and improve muscle strength. In these studies patients had advanced lung cancer and cachexia. Appendicular muscle was measured by DEXA scans and muscle strength by hand grip. Similar to enobosarm, anamorelin improved muscle mass but not the functional co-primary functional outcome, hand grip strength (182-184).

Resistance training

Some type of resistance training should be recommended. Resistance training increases type II muscle, improves strength, and directs protein intake toward muscle production. Resistance training forestalls age-related changes in mobility, improves gait speed, balance, and reduces fall risk in the elderly (185). There are differences in physiologic effects between aerobic and resistance training. Aerobic training alters mitochondrial and cytosolic enzyme activities, resistance exercise training increases contractile protein mass (186). It may be reasonable, therefore, to consider cross training between aerobic and resistance exercises. However, resistance training appears to be the most important element to an exercise program for patients undergoing therapy for their cancer. Early-stage breast cancer patients on adjuvant chemotherapy have a high risk of sarcopenia and dynapenia. Resistance training is superior to aerobic training in reversing both sarcopenia and dynapenia (187). Breast cancer patients undergoing hormone therapy have increased fat mass by 6 months, resistance training significantly increases LBM and fat free body mass (188). Resistance training decreases sarcopenia, reduces body fat, improves muscle strength and quality of life in hypogonadal prostate cancer patients, but not physical function (189).

Combination therapy

Combinations of medications or combinations of medications with resistance training has been reported. OMF supplementation of 2–4 g/day has been combined with resistance training. Both muscle strength and mass improved (190-193). These studies have almost exclusively been done in geriatric populations. The combination overcomes anabolic resistance that occurs in older individuals (194). A combination of vitamin D supplementation and a metabolite of leucine, calcium β-hydroxy β-methyl butyrate (CaHMB), improves muscle strength, grip and gait speed in randomized trials. It was most effective in patients with mild to moderate sarcopenia but not severe sarcopenia (195). This finding suggests that prevention approaches or early interventions are likely to be more successful. Vitamin D supplementation and whey protein rich in leucine increases appendicular skeletal muscle mass. Benefits are best seen in those with higher serum vitamin D levels (196). Whey protein should not be the only protein source. A combination of HMB, whey protein, vitamin D and exercise has improved muscle mass and strength in the elderly. Lasting impact will depend on baseline nutritional status, severity of sarcopenia prior to the intervention, and adherence to the intervention (197). In a small underpowered study of patients with lung cancer the combination of OMF and a cyclooxygenase inhibitor improved body weight, muscle strength and reduced C-reactive protein. The combination was better than OMF alone (165).


Sarcopenia is present at the beginning of chemotherapy in a subgroup of patients, and worsens or develops during neoadjuvant chemotherapy or palliative chemotherapy. Clinical outcomes are adversely influenced by the presence of sarcopenia prior to treatment or with the development of sarcopenia during therapy. Certain targeted agents cause sarcopenia while others may prevent or reverse sarcopenia. To treat and prevent sarcopenia, patients need adequate protein intake and resistance exercises. Patients should be screened for vitamin-D deficiency and vitamin-D should be replaced if deficient or insufficient. OMF 2–6 g/day should be considered as a supplement since toxicity is low and there are potential benefits. Large randomized trials are needed to validate the findings from small studies. Both anamorelin and enobosarm are unlikely to be approved to treat or present sarcopenia in cancer since neither one improved function. Combinations of protein supplements, OMF, HMB and exercise are promising but largely untested in cancer.




Conflicts of Interest: The authors have no conflicts of interest to declare.


  1. Baracos VE, Arribas L. Sarcopenic obesity: hidden muscle wasting and its impact for survival and complications of cancer therapy. Ann Oncol 2018;29:ii1-9. [Crossref] [PubMed]
  2. Fearon KC. Cancer cachexia and fat-muscle physiology. N Engl J Med 2011;365:565-7. [Crossref] [PubMed]
  3. Fearon K, Strasser F, Anker SD, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 2011;12:489-95. [Crossref] [PubMed]
  4. Mourtzakis M, Prado CM, Lieffers JR, et al. A practical and precise approach to quantification of body composition in cancer patients using computed tomography images acquired during routine care. Appl Physiol Nutr Metab 2008;33:997-1006. [Crossref] [PubMed]
  5. Del Fabbro E, Parsons H, Warneke CL, et al. The relationship between body composition and response to neoadjuvant chemotherapy in women with operable breast cancer. Oncologist 2012;17:1240-5. [Crossref] [PubMed]
  6. Dalal S, Hui D, Bidaut L, et al. Relationships among body mass index, longitudinal body composition alterations, and survival in patients with locally advanced pancreatic cancer receiving chemoradiation: a pilot study. J Pain Symptom Manage 2012;44:181-91. [Crossref] [PubMed]
  7. Prado CM, Lieffers JR, McCargar LJ, et al. Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol 2008;9:629-35. [Crossref] [PubMed]
  8. Rier HN, Jager A, Sleijfer S, et al. Low muscle attenuation is a prognostic factor for survival in metastatic breast cancer patients treated with first line palliative chemotherapy. Breast 2017;31:9-15. [Crossref] [PubMed]
  9. Rier HN, Jager A, Sleijfer S, et al. The Prevalence and Prognostic Value of Low Muscle Mass in Cancer Patients: A Review of the Literature. Oncologist 2016. [Epub ahead of print]. [Crossref] [PubMed]
  10. Martin L, Birdsell L, Macdonald N, et al. Cancer cachexia in the age of obesity: skeletal muscle depletion is a powerful prognostic factor, independent of body mass index. J Clin Oncol 2013;31:1539-47. [Crossref] [PubMed]
  11. Cruz-Jentoft AJ, Baeyens JP, Bauer JM, et al. Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing 2010;39:412-23. [Crossref] [PubMed]
  12. Cooper R, Kuh D, Cooper C, et al. Objective measures of physical capability and subsequent health: a systematic review. Age Ageing 2011;40:14-23. [Crossref] [PubMed]
  13. Cooper R, Kuh D, Hardy R, et al. Objectively measured physical capability levels and mortality: systematic review and meta-analysis. BMJ 2010;341:c4467. [Crossref] [PubMed]
  14. Aloia JF, McGowan DM, Vaswani AN, et al. Relationship of menopause to skeletal and muscle mass. Am J Clin Nutr 1991;53:1378-83. [Crossref] [PubMed]
  15. Hughes VA, Frontera WR, Roubenoff R, et al. Longitudinal changes in body composition in older men and women: role of body weight change and physical activity. Am J Clin Nutr 2002;76:473-81. [Crossref] [PubMed]
  16. Nair KS. Aging muscle. Am J Clin Nutr 2005;81:953-63. [Crossref] [PubMed]
  17. Clark BC, Manini TM. Sarcopenia =/= dynapenia. J Gerontol A Biol Sci Med Sci 2008;63:829-34. [Crossref] [PubMed]
  18. Sánchez-Lara K, Turcott JG, Juarez E, et al. Association of nutrition parameters including bioelectrical impedance and systemic inflammatory response with quality of life and prognosis in patients with advanced non-small-cell lung cancer: a prospective study. Nutr Cancer 2012;64:526-34. [Crossref] [PubMed]
  19. Prado CM, Lieffers JR, Bowthorpe L, et al. Sarcopenia and physical function in overweight patients with advanced cancer. Can J Diet Pract Res 2013;74:69-74. [Crossref] [PubMed]
  20. Pahor M, Manini T, Cesari M. Sarcopenia: clinical evaluation, biological markers and other evaluation tools. J Nutr Health Aging 2009;13:724-8. [Crossref] [PubMed]
  21. Peppa M, Stefanaki C, Papaefstathiou A, et al. Bioimpedance analysis vs. DEXA as a screening tool for osteosarcopenia in lean, overweight and obese Caucasian postmenopausal females. Hormones (Athens) 2017;16:181-93. [PubMed]
  22. Irlbeck T, Janitza S, Poros B, et al. Quantification of Adipose Tissue and Muscle Mass Based on Computed Tomography Scans: Comparison of Eight Planimetric and Diametric Techniques Including a Step-By-Step Guide. Eur Surg Res 2018;59:23-34. [Crossref] [PubMed]
  23. Rollins KE, Javanmard-Emamghissi H, Awwad A, et al. Body composition measurement using computed tomography: Does the phase of the scan matter? Nutrition 2017;41:37-44. [Crossref] [PubMed]
  24. Kinsey CM, San Jose Estepar R, van der Velden J, et al. Lower Pectoralis Muscle Area Is Associated with a Worse Overall Survival in Non-Small Cell Lung Cancer. Cancer Epidemiol Biomarkers Prev 2017;26:38-43. [Crossref] [PubMed]
  25. Hervochon R, Bobbio A, Guinet C, et al. Body Mass Index and Total Psoas Area Affect Outcomes in Patients Undergoing Pneumonectomy for Cancer. Ann Thorac Surg 2017;103:287-95. [Crossref] [PubMed]
  26. Derstine BA, Holcombe SA, Goulson RL, et al. Quantifying Sarcopenia Reference Values Using Lumbar and Thoracic Muscle Areas in a Healthy Population. J Nutr Health Aging 2017;21:180-5. [PubMed]
  27. Davis MP, Yavuzsen T, Khoshknabi D, et al. Bioelectrical impedance phase angle changes during hydration and prognosis in advanced cancer. Am J Hosp Palliat Care 2009;26:180-7. [Crossref] [PubMed]
  28. Hui D, Bansal S, Morgado M, et al. Phase angle for prognostication of survival in patients with advanced cancer: preliminary findings. Cancer 2014;120:2207-14. [Crossref] [PubMed]
  29. Gomez-Perez SL, Haus JM, Sheean P, et al. Measuring Abdominal Circumference and Skeletal Muscle From a Single Cross-Sectional Computed Tomography Image: A Step-by-Step Guide for Clinicians Using National Institutes of Health ImageJ. JPEN J Parenter Enteral Nutr 2016;40:308-18. [Crossref] [PubMed]
  30. Shen W, Punyanitya M, Wang Z, et al. Total body skeletal muscle and adipose tissue volumes: estimation from a single abdominal cross-sectional image. J Appl Physiol (1985) 2004;97:2333-8. [Crossref] [PubMed]
  31. Kodera Y. More than 6 months of postoperative adjuvant chemotherapy results in loss of skeletal muscle: a challenge to the current standard of care. Gastric Cancer 2015;18:203-4. [Crossref] [PubMed]
  32. Van Gammeren D, Damrauer JS, Jackman RW, et al. The IkappaB kinases IKKalpha and IKKbeta are necessary and sufficient for skeletal muscle atrophy. FASEB J 2009;23:362-70. [Crossref] [PubMed]
  33. Li YP, Reid MB. Effect of tumor necrosis factor-alpha on skeletal muscle metabolism. Curr Opin Rheumatol 2001;13:483-7. [Crossref] [PubMed]
  34. Gilliam LA, Moylan JS, Ferreira LF, et al. TNF/TNFR1 signaling mediates doxorubicin-induced diaphragm weakness. Am J Physiol Lung Cell Mol Physiol 2011;300:L225-31. [Crossref] [PubMed]
  35. Gilliam LA, Moylan JS, Callahan LA, et al. Doxorubicin causes diaphragm weakness in murine models of cancer chemotherapy. Muscle Nerve 2011;43:94-102. [Crossref] [PubMed]
  36. Chen JA, Splenser A, Guillory B, et al. Ghrelin prevents tumour- and cisplatin-induced muscle wasting: characterization of multiple mechanisms involved. J Cachexia Sarcopenia Muscle 2015;6:132-43. [Crossref] [PubMed]
  37. Gilliam LA, St Clair DK. Chemotherapy-induced weakness and fatigue in skeletal muscle: the role of oxidative stress. Antioxid Redox Signal 2011;15:2543-63. [Crossref] [PubMed]
  38. Chen JL, Colgan TD, Walton KL, et al. The TGF-beta Signalling Network in Muscle Development, Adaptation and Disease. Adv Exp Med Biol 2016;900:97-131. [Crossref] [PubMed]
  39. Ramesh G, Reeves WB. TNF-alpha mediates chemokine and cytokine expression and renal injury in cisplatin nephrotoxicity. J Clin Invest 2002;110:835-42. [Crossref] [PubMed]
  40. Barreto R, Waning DL, Gao H, et al. Chemotherapy-related cachexia is associated with mitochondrial depletion and the activation of ERK1/2 and p38 MAPKs. Oncotarget 2016;7:43442-60. [Crossref] [PubMed]
  41. Ederer AK, Didier KD, Reiter LK, et al. Influence of Adjuvant Therapy in Cancer Survivors on Endothelial Function and Skeletal Muscle Deoxygenation. PLoS One 2016;11:e0147691. [Crossref] [PubMed]
  42. Miyake M, Owari T, Iwamoto T, et al. Clinical utility of bioelectrical impedance analysis in patients with locoregional muscle invasive or metastatic urothelial carcinoma: a subanalysis of changes in body composition during neoadjuvant systemic chemotherapy. Support Care Cancer 2018;26:1077-86. [Crossref] [PubMed]
  43. Tan BH, Brammer K, Randhawa N, et al. Sarcopenia is associated with toxicity in patients undergoing neo-adjuvant chemotherapy for oesophago-gastric cancer. Eur J Surg Oncol 2015;41:333-8. [Crossref] [PubMed]
  44. Yip C, Goh V, Davies A, et al. Assessment of sarcopenia and changes in body composition after neoadjuvant chemotherapy and associations with clinical outcomes in oesophageal cancer. Eur Radiol 2014;24:998-1005. [Crossref] [PubMed]
  45. Miyata H, Sugimura K, Motoori M, et al. Clinical Assessment of Sarcopenia and Changes in Body Composition During Neoadjuvant Chemotherapy for Esophageal Cancer. Anticancer Res 2017;37:3053-9. [PubMed]
  46. Daly LE, Ni Bhuachalla EB, Power DG, et al. Loss of skeletal muscle during systemic chemotherapy is prognostic of poor survival in patients with foregut cancer. J Cachexia Sarcopenia Muscle 2018;9:315-25. [Crossref] [PubMed]
  47. Ní Bhuachalla ÉB, Daly LE, Power DG, et al. Computed tomography diagnosed cachexia and sarcopenia in 725 oncology patients: is nutritional screening capturing hidden malnutrition? J Cachexia Sarcopenia Muscle 2018;9:295-305. [Crossref] [PubMed]
  48. Versteeg KS, Blauwhoff-Buskermolen S, Buffart LM, et al. Higher Muscle Strength Is Associated with Prolonged Survival in Older Patients with Advanced Cancer. Oncologist 2018;23:580-5. [Crossref] [PubMed]
  49. Rier HN, Jager A, Meinardi MC, et al. Severe sarcopenia might be associated with a decline of physical independence in older patients undergoing chemotherapeutic treatment. Support Care Cancer 2018;26:1781-9. [Crossref] [PubMed]
  50. Stene GB, Helbostad JL, Amundsen T, et al. Changes in skeletal muscle mass during palliative chemotherapy in patients with advanced lung cancer. Acta Oncol 2015;54:340-8. [Crossref] [PubMed]
  51. Lanic H, Kraut-Tauzia J, Modzelewski R, et al. Sarcopenia is an independent prognostic factor in elderly patients with diffuse large B-cell lymphoma treated with immunochemotherapy. Leuk Lymphoma 2014;55:817-23. [Crossref] [PubMed]
  52. Miyamoto Y, Baba Y, Sakamoto Y, et al. Sarcopenia is a Negative Prognostic Factor After Curative Resection of Colorectal Cancer. Ann Surg Oncol 2015;22:2663-8. [Crossref] [PubMed]
  53. Harada K, Ida S, Baba Y, et al. Prognostic and clinical impact of sarcopenia in esophageal squamous cell carcinoma. Dis Esophagus 2016;29:627-33. [Crossref] [PubMed]
  54. van Vugt JLA, Buettner S, Levolger S, et al. Low skeletal muscle mass is associated with increased hospital expenditure in patients undergoing cancer surgery of the alimentary tract. PLoS One 2017;12:e0186547. [Crossref] [PubMed]
  55. van Vugt JL, Levolger S, de Bruin RW, et al. Systematic Review and Meta-Analysis of the Impact of Computed Tomography-Assessed Skeletal Muscle Mass on Outcome in Patients Awaiting or Undergoing Liver Transplantation. Am J Transplant 2016;16:2277-92. [Crossref] [PubMed]
  56. van Vugt JL, Levolger S, Coelen RJ, et al. The impact of sarcopenia on survival and complications in surgical oncology: A review of the current literature. J Surg Oncol 2015;112:681-2. [Crossref] [PubMed]
  57. Levolger S, van Vugt JL, de Bruin RW, et al. Systematic review of sarcopenia in patients operated on for gastrointestinal and hepatopancreatobiliary malignancies. Br J Surg 2015;102:1448-1458. [Crossref] [PubMed]
  58. van Vugt JL, Braam HJ, van Oudheusden TR, et al. Skeletal Muscle Depletion is Associated with Severe Postoperative Complications in Patients Undergoing Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis of Colorectal Cancer. Ann Surg Oncol 2015;22:3625-31. [Crossref] [PubMed]
  59. Fukushima H, Yokoyama M, Nakanishi Y, et al. Sarcopenia as a prognostic biomarker of advanced urothelial carcinoma. PLoS One 2015;10:e0115895. [Crossref] [PubMed]
  60. Voron T, Tselikas L, Pietrasz D, et al. Sarcopenia Impacts on Short- and Long-term Results of Hepatectomy for Hepatocellular Carcinoma. Ann Surg 2015;261:1173-83. [Crossref] [PubMed]
  61. Tegels JJ, van Vugt JL, Reisinger KW, et al. Sarcopenia is highly prevalent in patients undergoing surgery for gastric cancer but not associated with worse outcomes. J Surg Oncol 2015;112:403-7. [Crossref] [PubMed]
  62. Reisinger KW, Bosmans JW, Uittenbogaart M, et al. Loss of Skeletal Muscle Mass During Neoadjuvant Chemoradiotherapy Predicts Postoperative Mortality in Esophageal Cancer Surgery. Ann Surg Oncol 2015;22:4445-52. [Crossref] [PubMed]
  63. Reisinger KW, van Vugt JL, Tegels JJ, et al. Functional compromise reflected by sarcopenia, frailty, and nutritional depletion predicts adverse postoperative outcome after colorectal cancer surgery. Ann Surg 2015;261:345-52. [Crossref] [PubMed]
  64. Dello SA, Lodewick TM, van Dam RM, et al. Sarcopenia negatively affects preoperative total functional liver volume in patients undergoing liver resection. HPB (Oxford) 2013;15:165-9. [Crossref] [PubMed]
  65. Shirai H, Kaido T, Hamaguchi Y, et al. Preoperative low muscle mass has a strong negative effect on pulmonary function in patients undergoing living donor liver transplantation. Nutrition 2018;45:1-10. [Crossref] [PubMed]
  66. Okumura S, Kaido T, Hamaguchi Y, et al. Impact of Skeletal Muscle Mass, Muscle Quality, and Visceral Adiposity on Outcomes Following Resection of Intrahepatic Cholangiocarcinoma. Ann Surg Oncol 2017;24:1037-45. [Crossref] [PubMed]
  67. Okumura S, Kaido T, Hamaguchi Y, et al. Impact of the preoperative quantity and quality of skeletal muscle on outcomes after resection of extrahepatic biliary malignancies. Surgery 2016;159:821-33. [Crossref] [PubMed]
  68. Okumura S, Kaido T, Hamaguchi Y, et al. Impact of preoperative quality as well as quantity of skeletal muscle on survival after resection of pancreatic cancer. Surgery 2015;157:1088-98. [Crossref] [PubMed]
  69. Chu MP, Lieffers J, Ghosh S, et al. Skeletal muscle density is an independent predictor of diffuse large B-cell lymphoma outcomes treated with rituximab-based chemoimmunotherapy. J Cachexia Sarcopenia Muscle 2017;8:298-304. [Crossref] [PubMed]
  70. Meza-Junco J, Montano-Loza AJ, Baracos VE, et al. Sarcopenia as a prognostic index of nutritional status in concurrent cirrhosis and hepatocellular carcinoma. J Clin Gastroenterol 2013;47:861-70. [Crossref] [PubMed]
  71. Lieffers JR, Bathe OF, Fassbender K, et al. Sarcopenia is associated with postoperative infection and delayed recovery from colorectal cancer resection surgery. Br J Cancer 2012;107:931-6. [Crossref] [PubMed]
  72. Peng PD, van Vledder MG, Tsai S, et al. Sarcopenia negatively impacts short-term outcomes in patients undergoing hepatic resection for colorectal liver metastasis. HPB (Oxford) 2011;13:439-46. [Crossref] [PubMed]
  73. Peng P, Hyder O, Firoozmand A, et al. Impact of sarcopenia on outcomes following resection of pancreatic adenocarcinoma. J Gastrointest Surg 2012;16:1478-86. [Crossref] [PubMed]
  74. Kiyotoki T, Nakamura K, Haraga J, et al. Sarcopenia Is an Important Prognostic Factor in Patients With Cervical Cancer Undergoing Concurrent Chemoradiotherapy. Int J Gynecol Cancer 2018;28:168-75. [Crossref] [PubMed]
  75. Ida S, Watanabe M, Yoshida N, et al. Sarcopenia is a Predictor of Postoperative Respiratory Complications in Patients with Esophageal Cancer. Ann Surg Oncol 2015;22:4432-7. [Crossref] [PubMed]
  76. Correa-de-Araujo R, Harris-Love MO, Miljkovic I, et al. The Need for Standardized Assessment of Muscle Quality in Skeletal Muscle Function Deficit and Other Aging-Related Muscle Dysfunctions: A Symposium Report. Front Physiol 2017;8:87. [Crossref] [PubMed]
  77. Sueda T, Takahasi H, Nishimura J, et al. Impact of Low Muscularity and Myosteatosis on Long-term Outcome After Curative Colorectal Cancer Surgery: A Propensity Score-Matched Analysis. Dis Colon Rectum 2018;61:364-74. [PubMed]
  78. Miljkovic I, Zmuda JM. Epidemiology of myosteatosis. Curr Opin Clin Nutr Metab Care 2010;13:260-4. [Crossref] [PubMed]
  79. Zoico E, Corzato F, Bambace C, et al. Myosteatosis and myofibrosis: relationship with aging, inflammation and insulin resistance. Arch Gerontol Geriatr 2013;57:411-6. [Crossref] [PubMed]
  80. Lang T, Cauley JA, Tylavsky F, et al. Computed tomographic measurements of thigh muscle cross-sectional area and attenuation coefficient predict hip fracture: the health, aging, and body composition study. J Bone Miner Res 2010;25:513-9. [Crossref] [PubMed]
  81. Ewaschuk JB, Almasud A, Mazurak VC. Role of n-3 fatty acids in muscle loss and myosteatosis. Appl Physiol Nutr Metab 2014;39:654-62. [Crossref] [PubMed]
  82. van Dijk DPJ, Bakers FCH, Sanduleanu S, et al. Myosteatosis predicts survival after surgery for periampullary cancer: a novel method using MRI. HPB (Oxford) 2018;20:715-20. [Crossref] [PubMed]
  83. Rollins KE, Tewari N, Ackner A, et al. The impact of sarcopenia and myosteatosis on outcomes of unresectable pancreatic cancer or distal cholangiocarcinoma. Clin Nutr 2016;35:1103-9. [Crossref] [PubMed]
  84. Kaibori M, Ishizaki M, Iida H, et al. Effect of Intramuscular Adipose Tissue Content on Prognosis in Patients Undergoing Hepatocellular Carcinoma Resection. J Gastrointest Surg 2015;19:1315-23. [Crossref] [PubMed]
  85. Almasud AA, Giles KH, Miklavcic JJ, et al. Fish oil mitigates myosteatosis and improves chemotherapy efficacy in a preclinical model of colon cancer. PLoS One 2017;12:e0183576. [Crossref] [PubMed]
  86. Rier HN, Jager A, Sleijfer S, et al. Changes in body composition and muscle attenuation during taxane-based chemotherapy in patients with metastatic breast cancer. Breast Cancer Res Treat 2018;168:95-105. [Crossref] [PubMed]
  87. Nattenmüller J, Wochner R, Muley T, et al. Prognostic Impact of CT-Quantified Muscle and Fat Distribution before and after First-Line-Chemotherapy in Lung Cancer Patients. PLoS One 2017;12:e0169136. [Crossref] [PubMed]
  88. Stanisavljevic NS, Marisavljevic DZ. Weight and body composition changes during R-CHOP chemotherapy in patients with non-Hodgkin's lymphoma and their impact on dose intensity and toxicity. J BUON 2010;15:290-6. [PubMed]
  89. Okumura S, Kaido T, Hamaguchi Y, et al. Visceral Adiposity and Sarcopenic Visceral Obesity are Associated with Poor Prognosis After Resection of Pancreatic Cancer. Ann Surg Oncol 2017;24:3732-40. [Crossref] [PubMed]
  90. Yip C, Dinkel C, Mahajan A, et al. Imaging body composition in cancer patients: visceral obesity, sarcopenia and sarcopenic obesity may impact on clinical outcome. Insights Imaging 2015;6:489-97. [Crossref] [PubMed]
  91. Tan BH, Birdsell LA, Martin L, et al. Sarcopenia in an overweight or obese patient is an adverse prognostic factor in pancreatic cancer. Clin Cancer Res 2009;15:6973-9. [Crossref] [PubMed]
  92. Pecorelli N, Carrara G, De Cobelli F, et al. Effect of sarcopenia and visceral obesity on mortality and pancreatic fistula following pancreatic cancer surgery. Br J Surg 2016;103:434-42. [Crossref] [PubMed]
  93. Awad S, Tan BH, Cui H, et al. Marked changes in body composition following neoadjuvant chemotherapy for oesophagogastric cancer. Clin Nutr 2012;31:74-7. [Crossref] [PubMed]
  94. Anandavadivelan P, Brismar TB, Nilsson M, et al. Sarcopenic obesity: A probable risk factor for dose limiting toxicity during neo-adjuvant chemotherapy in oesophageal cancer patients. Clin Nutr 2016;35:724-30. [Crossref] [PubMed]
  95. Palmela C, Velho S, Agostinho L, et al. Body Composition as a Prognostic Factor of Neoadjuvant Chemotherapy Toxicity and Outcome in Patients with Locally Advanced Gastric Cancer. J Gastric Cancer 2017;17:74-87. [Crossref] [PubMed]
  96. Prado CM, Cushen SJ, Orsso CE, et al. Sarcopenia and cachexia in the era of obesity: clinical and nutritional impact. Proc Nutr Soc 2016;75:188-98. [Crossref] [PubMed]
  97. Lou N, Chi CH, Chen XD, et al. Sarcopenia in overweight and obese patients is a predictive factor for postoperative complication in gastric cancer: A prospective study. Eur J Surg Oncol 2017;43:188-95. [Crossref] [PubMed]
  98. Nishigori T, Tsunoda S, Okabe H, et al. Impact of Sarcopenic Obesity on Surgical Site Infection after Laparoscopic Total Gastrectomy. Ann Surg Oncol 2016;23:524-31. [Crossref] [PubMed]
  99. Kakinuma K, Tsuruoka H, Morikawa K, et al. Differences in skeletal muscle loss caused by cytotoxic chemotherapy and molecular targeted therapy in patients with advanced non-small cell lung cancer. Thorac Cancer 2018;9:99-104. [Crossref] [PubMed]
  100. Barreiro E, Gea J. PARP-1 and PARP-2 activity in cancer-induced cachexia: potential therapeutic implications. Biol Chem 2018;399:179-86. [Crossref] [PubMed]
  101. Mohamed JS, Wilson JC, Myers MJ, et al. Dysregulation of SIRT-1 in aging mice increases skeletal muscle fatigue by a PARP-1-dependent mechanism. Aging (Albany NY) 2014;6:820-34. [Crossref] [PubMed]
  102. Chacon-Cabrera A, Mateu-Jimenez M, Langohr K, et al. Role of PARP activity in lung cancer-induced cachexia: Effects on muscle oxidative stress, proteolysis, anabolic markers, and phenotype. J Cell Physiol 2017;232:3744-61. [Crossref] [PubMed]
  103. Pirinen E, Canto C, Jo YS, et al. Pharmacological Inhibition of poly(ADP-ribose) polymerases improves fitness and mitochondrial function in skeletal muscle. Cell Metab 2014;19:1034-41. [Crossref] [PubMed]
  104. Cantó C, Sauve AA, Bai P. Crosstalk between poly(ADP-ribose) polymerase and sirtuin enzymes. Mol Aspects Med 2013;34:1168-201. [Crossref] [PubMed]
  105. Bai P, Canto C, Oudart H, et al. PARP-1 inhibition increases mitochondrial metabolism through SIRT1 activation. Cell Metab 2011;13:461-8. [Crossref] [PubMed]
  106. Bai P, Canto C, Brunyanszki A, et al. PARP-2 regulates SIRT1 expression and whole-body energy expenditure. Cell Metab 2011;13:450-60. [Crossref] [PubMed]
  107. Quan-Jun Y, Yan H, Yong-Long H, et al. Selumetinib Attenuates Skeletal Muscle Wasting in Murine Cachexia Model through ERK Inhibition and AKT Activation. Mol Cancer Ther 2017;16:334-43. [Crossref] [PubMed]
  108. Prado CM, Bekaii-Saab T, Doyle LA, et al. Skeletal muscle anabolism is a side effect of therapy with the MEK inhibitor: selumetinib in patients with cholangiocarcinoma. Br J Cancer 2012;106:1583-6. [Crossref] [PubMed]
  109. Bekaii-Saab T, Phelps MA, Li X, et al. Multi-institutional phase II study of selumetinib in patients with metastatic biliary cancers. J Clin Oncol 2011;29:2357-63. [Crossref] [PubMed]
  110. Ito T, Ogawa R, Uezumi A, et al. Imatinib attenuates severe mouse dystrophy and inhibits proliferation and fibrosis-marker expression in muscle mesenchymal progenitors. Neuromuscul Disord 2013;23:349-56. [Crossref] [PubMed]
  111. Moryoussef F, Dhooge M, Volet J, et al. Reversible sarcopenia in patients with gastrointestinal stromal tumor treated with imatinib. J Cachexia Sarcopenia Muscle 2015;6:343-50. [Crossref] [PubMed]
  112. Toledo M, Penna F, Oliva F, et al. A multifactorial anti-cachectic approach for cancer cachexia in a rat model undergoing chemotherapy. J Cachexia Sarcopenia Muscle 2016;7:48-59. [Crossref] [PubMed]
  113. Antoun S, Birdsell L, Sawyer MB, et al. Association of skeletal muscle wasting with treatment with sorafenib in patients with advanced renal cell carcinoma: results from a placebo-controlled study. J Clin Oncol 2010;28:1054-60. [Crossref] [PubMed]
  114. Nishikawa H, Nishijima N, Enomoto H, et al. Prognostic significance of sarcopenia in patients with hepatocellular carcinoma undergoing sorafenib therapy. Oncol Lett 2017;14:1637-47. [Crossref] [PubMed]
  115. Mir O, Coriat R, Blanchet B, et al. Sarcopenia predicts early dose-limiting toxicities and pharmacokinetics of sorafenib in patients with hepatocellular carcinoma. PLoS One 2012;7:e37563. [Crossref] [PubMed]
  116. Antoun S, Baracos VE, Birdsell L, et al. Low body mass index and sarcopenia associated with dose-limiting toxicity of sorafenib in patients with renal cell carcinoma. Ann Oncol 2010;21:1594-8. [Crossref] [PubMed]
  117. Nault JC, Pigneur F, Nelson AC, et al. Visceral fat area predicts survival in patients with advanced hepatocellular carcinoma treated with tyrosine kinase inhibitors. Dig Liver Dis 2015;47:869-76. [Crossref] [PubMed]
  118. Ladoire S, Bonnetain F, Gauthier M, et al. Visceral fat area as a new independent predictive factor of survival in patients with metastatic renal cell carcinoma treated with antiangiogenic agents. Oncologist 2011;16:71-81. [Crossref] [PubMed]
  119. Steffens S, Grunwald V, Ringe KI, et al. Does obesity influence the prognosis of metastatic renal cell carcinoma in patients treated with vascular endothelial growth factor-targeted therapy? Oncologist 2011;16:1565-71. [Crossref] [PubMed]
  120. Ishihara H, Kondo T, Omae K, et al. Sarcopenia and the Modified Glasgow Prognostic Score are Significant Predictors of Survival Among Patients with Metastatic Renal Cell Carcinoma Who are Receiving First-Line Sunitinib Treatment. Target Oncol 2016;11:605-17. [Crossref] [PubMed]
  121. Huillard O, Mir O, Peyromaure M, et al. Sarcopenia and body mass index predict sunitinib-induced early dose-limiting toxicities in renal cancer patients. Br J Cancer 2013;108:1034-41. [Crossref] [PubMed]
  122. Cushen SJ, Power DG, Teo MY, et al. Body Composition by Computed Tomography as a Predictor of Toxicity in Patients With Renal Cell Carcinoma Treated With Sunitinib. Am J Clin Oncol 2017;40:47-52. [Crossref] [PubMed]
  123. Gyawali B, Shimokata T, Honda K, et al. Muscle wasting associated with the long-term use of mTOR inhibitors. Mol Clin Oncol 2016;5:641-6. [Crossref] [PubMed]
  124. Auclin E, Bourillon C, De Maio E, et al. Prediction of Everolimus Toxicity and Prognostic Value of Skeletal Muscle Index in Patients With Metastatic Renal Cell Carcinoma. Clin Genitourin Cancer 2017;15:350-5. [Crossref] [PubMed]
  125. Baracos VE. Skeletal muscle anabolism in patients with advanced cancer. Lancet Oncol 2015;16:13-4. [Crossref] [PubMed]
  126. MacDonald AJ, Johns N, Stephens N, et al. Habitual Myofibrillar Protein Synthesis Is Normal in Patients with Upper GI Cancer Cachexia. Clin Cancer Res 2015;21:1734-40. [Crossref] [PubMed]
  127. Deutz NE, Safar A, Schutzler S, et al. Muscle protein synthesis in cancer patients can be stimulated with a specially formulated medical food. Clin Nutr 2011;30:759-68. [Crossref] [PubMed]
  128. Garcia JM, Boccia RV, Graham CD, et al. Anamorelin for patients with cancer cachexia: an integrated analysis of two phase 2, randomised, placebo-controlled, double-blind trials. Lancet Oncol 2015;16:108-16. [Crossref] [PubMed]
  129. Dobs AS, Boccia RV, Croot CC, et al. Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial. Lancet Oncol 2013;14:335-45. [Crossref] [PubMed]
  130. Deutz NE, Bauer JM, Barazzoni R, et al. Protein intake and exercise for optimal muscle function with aging: recommendations from the ESPEN Expert Group. Clin Nutr 2014;33:929-36. [Crossref] [PubMed]
  131. Bauer J, Biolo G, Cederholm T, et al. Evidence-based recommendations for optimal dietary protein intake in older people: a position paper from the PROT-AGE Study Group. J Am Med Dir Assoc 2013;14:542-59. [Crossref] [PubMed]
  132. McDonald CK, Ankarfeldt MZ, Capra S, et al. Lean body mass change over 6 years is associated with dietary leucine intake in an older Danish population. Br J Nutr 2016;115:1556-62. [Crossref] [PubMed]
  133. Morley JE, Argiles JM, Evans WJ, et al. Nutritional recommendations for the management of sarcopenia. J Am Med Dir Assoc 2010;11:391-6. [Crossref] [PubMed]
  134. Komar B, Schwingshackl L, Hoffmann G. Effects of leucine-rich protein supplements on anthropometric parameter and muscle strength in the elderly: a systematic review and meta-analysis. J Nutr Health Aging 2015;19:437-46. [Crossref] [PubMed]
  135. Elango R, Rasmussen B, Madden K. Safety and Tolerability of Leucine Supplementation in Elderly Men. J Nutr 2016;146:2630S-4S. [Crossref] [PubMed]
  136. Vallejo J, Spence M, Cheng AL, et al. Cellular and Physiological Effects of Dietary Supplementation with beta-Hydroxy-beta-Methylbutyrate (HMB) and beta-Alanine in Late Middle-Aged Mice. PLoS One 2016;11:e0150066. [Crossref] [PubMed]
  137. Alway SE, Pereira SL, Edens NK, et al. beta-Hydroxy-beta-methylbutyrate (HMB) enhances the proliferation of satellite cells in fast muscles of aged rats during recovery from disuse atrophy. Exp Gerontol 2013;48:973-84. [Crossref] [PubMed]
  138. Stout JR, Smith-Ryan AE, Fukuda DH, et al. Effect of calcium beta-hydroxy-beta-methylbutyrate (CaHMB) with and without resistance training in men and women 65+yrs:a randomized, double-blind pilot trial. Exp Gerontol 2013;48:1303-10. [Crossref] [PubMed]
  139. Wu H, Xia Y, Jiang J, et al. Effect of beta-hydroxy-beta-methylbutyrate supplementation on muscle loss in older adults: a systematic review and meta-analysis. Arch Gerontol Geriatr 2015;61:168-75. [Crossref] [PubMed]
  140. Holeček M. Beta-hydroxy-beta-methylbutyrate supplementation and skeletal muscle in healthy and muscle-wasting conditions. J Cachexia Sarcopenia Muscle 2017;8:529-41. [Crossref] [PubMed]
  141. Abiri B, Vafa M. Nutrition and sarcopenia: A review of the evidence of nutritional influences. Crit Rev Food Sci Nutr 2017.1-11. [Epub ahead of print]. [Crossref] [PubMed]
  142. Arends J, Bachmann P, Baracos V, et al. ESPEN guidelines on nutrition in cancer patients. Clin Nutr 2017;36:11-48. [Crossref] [PubMed]
  143. Cruz-Jentoft AJ, Kiesswetter E, Drey M, et al. Nutrition, frailty, and sarcopenia. Aging Clin Exp Res 2017;29:43-8. [Crossref] [PubMed]
  144. de Vries YC, Boesveldt S, Kelfkens CS, et al. Taste and smell perception and quality of life during and after systemic therapy for breast cancer. Breast Cancer Res Treat 2018;170:27-34. [Crossref] [PubMed]
  145. Ponticelli E, Clari M, Frigerio S, et al. Dysgeusia and health-related quality of life of cancer patients receiving chemotherapy: A cross-sectional study. Eur J Cancer Care (Engl) 2017.26. [PubMed]
  146. Brisbois TD, de Kock IH, Watanabe SM, et al. Delta-9-tetrahydrocannabinol may palliate altered chemosensory perception in cancer patients: results of a randomized, double-blind, placebo-controlled pilot trial. Ann Oncol 2011;22:2086-93. [Crossref] [PubMed]
  147. Rolland Y, Dupuy C, Abellan van Kan G, et al. Treatment strategies for sarcopenia and frailty. Med Clin North Am 2011;95:427-38. ix. [Crossref] [PubMed]
  148. Iolascon G, de Sire A, Calafiore D, et al. Hypovitaminosis D is associated with a reduction in upper and lower limb muscle strength and physical performance in post-menopausal women: a retrospective study. Aging Clin Exp Res 2015;27 Suppl 1:S23-30. [Crossref] [PubMed]
  149. Mastaglia SR, Seijo M, Muzio D, et al. Effect of vitamin D nutritional status on muscle function and strength in healthy women aged over sixty-five years. J Nutr Health Aging 2011;15:349-54. [Crossref] [PubMed]
  150. Ensrud KE, Blackwell TL, Cauley JA, et al. Circulating 25-hydroxyvitamin D levels and frailty in older men: the osteoporotic fractures in men study. J Am Geriatr Soc 2011;59:101-6. [Crossref] [PubMed]
  151. Visser M, Deeg DJ, Lips P. Longitudinal Aging Study A. Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia): the Longitudinal Aging Study Amsterdam. J Clin Endocrinol Metab 2003;88:5766-72. [Crossref] [PubMed]
  152. Ceglia L, Niramitmahapanya S, da Silva Morais M, et al. A randomized study on the effect of vitamin D(3) supplementation on skeletal muscle morphology and vitamin D receptor concentration in older women. J Clin Endocrinol Metab 2013;98:E1927-35. [Crossref] [PubMed]
  153. Ceglia L, Chiu GR, Harris SS, et al. Serum 25-hydroxyvitamin D concentration and physical function in adult men. Clin Endocrinol (Oxf) 2011;74:370-6. [Crossref] [PubMed]
  154. van der Wielen RP, Lowik MR, van den Berg H, et al. Serum vitamin D concentrations among elderly people in Europe. Lancet 1995;346:207-10. [Crossref] [PubMed]
  155. Wagatsuma A, Sakuma K. Vitamin D signaling in myogenesis: potential for treatment of sarcopenia. Biomed Res Int 2014;2014:121254. [Crossref] [PubMed]
  156. Yoshikawa S. Vitamin D resistant osteomalacia. Seikei Geka 1970;21:757-67. [PubMed]
  157. Morley JE. Hormones and Sarcopenia. Curr Pharm Des 2017;23:4484-92. [Crossref] [PubMed]
  158. Dastur DK, Gagrat BM, Wadia NH, et al. Nature of muscular change in osteomalacia: light- and electron-microscope observations. J Pathol 1975;117:211-28. [Crossref] [PubMed]
  159. Murphy RA, Mourtzakis M, Chu QS, et al. Supplementation with fish oil increases first-line chemotherapy efficacy in patients with advanced nonsmall cell lung cancer. Cancer 2011;117:3774-80. [Crossref] [PubMed]
  160. Yasuda M, Tanaka Y, Kume S, et al. Fatty acids are novel nutrient factors to regulate mTORC1 lysosomal localization and apoptosis in podocytes. Biochim Biophys Acta 2014;1842:1097-108. [Crossref] [PubMed]
  161. Gingras AA, White PJ, Chouinard PY, et al. Long-chain omega-3 fatty acids regulate bovine whole-body protein metabolism by promoting muscle insulin signalling to the Akt-mTOR-S6K1 pathway and insulin sensitivity. J Physiol 2007;579:269-84. [Crossref] [PubMed]
  162. Smith GI, Atherton P, Reeds DN, et al. Omega-3 polyunsaturated fatty acids augment the muscle protein anabolic response to hyperinsulinaemia-hyperaminoacidaemia in healthy young and middle-aged men and women. Clin Sci (Lond) 2011;121:267-78. [Crossref] [PubMed]
  163. Shin SK, Kim JH, Lee JH, et al. Docosahexaenoic acid-mediated protein aggregates may reduce proteasome activity and delay myotube degradation during muscle atrophy in vitro. Exp Mol Med 2017;49:e287. [Crossref] [PubMed]
  164. Wójcik C, Lohe K, Kuang C, et al. Modulation of adipocyte differentiation by omega-3 polyunsaturated fatty acids involves the ubiquitin-proteasome system. J Cell Mol Med 2014;18:590-9. [Crossref] [PubMed]
  165. Cerchietti LC, Navigante AH, Castro MA. Effects of eicosapentaenoic and docosahexaenoic n-3 fatty acids from fish oil and preferential Cox-2 inhibition on systemic syndromes in patients with advanced lung cancer. Nutr Cancer 2007;59:14-20. [Crossref] [PubMed]
  166. Bougnoux P, Hajjaji N, Ferrasson MN, et al. Improving outcome of chemotherapy of metastatic breast cancer by docosahexaenoic acid: a phase II trial. Br J Cancer 2009;101:1978-85. [Crossref] [PubMed]
  167. Sánchez-Lara K, Turcott JG, Juarez-Hernandez E, et al. Effects of an oral nutritional supplement containing eicosapentaenoic acid on nutritional and clinical outcomes in patients with advanced non-small cell lung cancer: randomised trial. Clin Nutr 2014;33:1017-23. [Crossref] [PubMed]
  168. Murphy RA, Mourtzakis M, Chu QS, et al. Nutritional intervention with fish oil provides a benefit over standard of care for weight and skeletal muscle mass in patients with nonsmall cell lung cancer receiving chemotherapy. Cancer 2011;117:1775-82. [Crossref] [PubMed]
  169. Wright TJ, Dillon EL, Durham WJ, et al. A randomized trial of adjunct testosterone for cancer-related muscle loss in men and women. J Cachexia Sarcopenia Muscle 2018;9:482-96. [Crossref] [PubMed]
  170. Basaria S, Coviello AD, Travison TG, et al. Adverse events associated with testosterone administration. N Engl J Med 2010;363:109-22. [Crossref] [PubMed]
  171. Narayanan R, Coss CC, Dalton JT. Development of selective androgen receptor modulators (SARMs). Mol Cell Endocrinol 2018;465:134-42. [Crossref] [PubMed]
  172. Srinath R, Dobs A. Enobosarm (GTx-024, S-22): a potential treatment for cachexia. Future Oncol 2014;10:187-94. [Crossref] [PubMed]
  173. Chen J, Hwang DJ, Bohl CE, et al. A selective androgen receptor modulator for hormonal male contraception. J Pharmacol Exp Ther 2005;312:546-53. [Crossref] [PubMed]
  174. Kazmin D, Prytkova T, Cook CE, et al. Linking ligand-induced alterations in androgen receptor structure to differential gene expression: a first step in the rational design of selective androgen receptor modulators. Mol Endocrinol 2006;20:1201-17. [Crossref] [PubMed]
  175. Aikawa K, Asano M, Ono K, et al. Synthesis and biological evaluation of novel selective androgen receptor modulators (SARMs) Part III: Discovery of 4-(5-oxopyrrolidine-1-yl)benzonitrile derivative 2f as a clinical candidate. Bioorg Med Chem 2017;25:3330-49. [Crossref] [PubMed]
  176. Asano M, Hitaka T, Imada T, et al. Synthesis and biological evaluation of novel selective androgen receptor modulators (SARMs). Part II: Optimization of 4-(pyrrolidin-1-yl)benzonitrile derivatives. Bioorg Med Chem Lett 2017;27:1897-901. [Crossref] [PubMed]
  177. Le-Rademacher JG, Crawford J, Evans WJ, et al. Overcoming obstacles in the design of cancer anorexia/weight loss trials. Crit Rev Oncol Hematol 2017;117:30-7. [Crossref] [PubMed]
  178. Dalton JT, Taylor RP, Mohler ML, et al. Selective androgen receptor modulators for the prevention and treatment of muscle wasting associated with cancer. Curr Opin Support Palliat Care 2013;7:345-51. [Crossref] [PubMed]
  179. Crawford J, Prado CM, Johnston MA, et al. Study Design and Rationale for the Phase 3 Clinical Development Program of Enobosarm, a Selective Androgen Receptor Modulator, for the Prevention and Treatment of Muscle Wasting in Cancer Patients (POWER Trials). Curr Oncol Rep 2016;18:37. [Crossref] [PubMed]
  180. Briggs DI, Andrews ZB. Metabolic status regulates ghrelin function on energy homeostasis. Neuroendocrinology 2011;93:48-57. [Crossref] [PubMed]
  181. Conte E, Camerino GM, Mele A, et al. Growth hormone secretagogues prevent dysregulation of skeletal muscle calcium homeostasis in a rat model of cisplatin-induced cachexia. J Cachexia Sarcopenia Muscle 2017;8:386-404. [Crossref] [PubMed]
  182. Takayama K, Katakami N, Yokoyama T, et al. Anamorelin (ONO-7643) in Japanese patients with non-small cell lung cancer and cachexia: results of a randomized phase 2 trial. Support Care Cancer 2016;24:3495-505. [Crossref] [PubMed]
  183. Temel JS, Abernethy AP, Currow DC, et al. Anamorelin in patients with non-small-cell lung cancer and cachexia (ROMANA 1 and ROMANA 2): results from two randomised, double-blind, phase 3 trials. Lancet Oncol 2016;17:519-31. [Crossref] [PubMed]
  184. Northrup R, Kuroda K, Duus EM, et al. Effect of ghrelin and anamorelin (ONO-7643), a selective ghrelin receptor agonist, on tumor growth in a lung cancer mouse xenograft model. Support Care Cancer 2013;21:2409-15. [Crossref] [PubMed]
  185. Papa EV, Dong X, Hassan M. Resistance training for activity limitations in older adults with skeletal muscle function deficits: a systematic review. Clin Interv Aging 2017;12:955-61. [Crossref] [PubMed]
  186. Zinna EM, Yarasheski KE. Exercise treatment to counteract protein wasting of chronic diseases. Curr Opin Clin Nutr Metab Care 2003;6:87-93. [Crossref] [PubMed]
  187. Adams SC, Segal RJ, McKenzie DC, et al. Impact of resistance and aerobic exercise on sarcopenia and dynapenia in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial. Breast Cancer Res Treat 2016;158:497-507. [Crossref] [PubMed]
  188. Hojan K, Milecki P, Molinska-Glura M, et al. Effect of physical activity on bone strength and body composition in breast cancer premenopausal women during endocrine therapy. Eur J Phys Rehabil Med 2013;49:331-9. [PubMed]
  189. Dawson JK, Dorff TB, Todd Schroeder E, et al. Impact of resistance training on body composition and metabolic syndrome variables during androgen deprivation therapy for prostate cancer: a pilot randomized controlled trial. BMC Cancer 2018;18:368. [Crossref] [PubMed]
  190. De Spiegeleer A, Petrovic M, Boeckxstaens P, Van Den Noortgate N. Treating sarcopenia in clinical practice: where are we now? Acta Clin Belg 2016;71:197-205. [Crossref] [PubMed]
  191. Phillips SM. Nutritional supplements in support of resistance exercise to counter age-related sarcopenia. Adv Nutr 2015;6:452-60. [Crossref] [PubMed]
  192. Rodacki CL, Rodacki AL, Pereira G, et al. Fish-oil supplementation enhances the effects of strength training in elderly women. Am J Clin Nutr 2012;95:428-36. [Crossref] [PubMed]
  193. Volkert D. The role of nutrition in the prevention of sarcopenia. Wien Med Wochenschr 2011;161:409-15. [Crossref] [PubMed]
  194. Smith A. Sarcopenia, malnutrition and nutrient density in older people. Post Reprod Health 2014;20:19-21. [Crossref] [PubMed]
  195. Cramer JT, Cruz-Jentoft AJ, Landi F, et al. Impacts of High-Protein Oral Nutritional Supplements Among Malnourished Men and Women with Sarcopenia: A Multicenter, Randomized, Double-Blinded, Controlled Trial. J Am Med Dir Assoc 2016;17:1044-55. [Crossref] [PubMed]
  196. Verlaan S, Maier AB, Bauer JM, et al. Sufficient levels of 25-hydroxyvitamin D and protein intake required to increase muscle mass in sarcopenic older adults - The PROVIDE study. Clin Nutr 2018;37:551-7. [Crossref] [PubMed]
  197. Woo J. Nutritional interventions in sarcopenia: where do we stand? Curr Opin Clin Nutr Metab Care 2018;21:19-23. [Crossref] [PubMed]
Cite this article as: Davis MP, Panikkar R. Sarcopenia associated with chemotherapy and targeted agents for cancer therapy. Ann Palliat Med 2019;8(1):86-101. doi: 10.21037/apm.2018.08.02

Download Citation