An exploratory study of body composition as a determinant of epirubicin pharmacokinetics and toxicity

Prado, Carla M.; Lima, Isac; Baracos, Vickie E.; Bies, Robert R.; McCargar, Linda J.; Reiman, Tony; Mackey, John R.; Kuzma, Michelle; Damaraju, Vijaya L.; Sawyer, Michael B.

doi:10.1007/s00280-010-1288-y

Cited by 144 publications

(124 citation statements)

References 27 publications

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“…2) would consequently be receiving exactly the same amount of chemotherapy drug (31) . Such practice ignores the large individual variability in muscle mass and hence lean tissue compartment, where pharmacokinetics (drug metabolism) occurs (32)(33)(34)(35) . This concept has been extensively reviewed previously and we refer the reader to other articles for a more detailed discussion (31,32) .…”

Section: Treatment Toxicitymentioning

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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Section: Treatment Toxicitymentioning

confidence: 99%

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

et al. 2016

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“…Body composition was analysed using a pre-treatment CT scan, as previously described in other reports [17,18]. Muscle tissues were identified on CT images and analysed using ImageJ software version 1.42q (National Institutes of Health, http://rsb.info.nih.gov/ij).…”

Section: Methodsmentioning

confidence: 99%

Feasibility of Gemcitabine plus Oxaliplatin in Advanced Hepatocellular Carcinoma Patients with Child-Pugh B Cirrhosis

Dhooge¹,

Mir

Perkins

et al. 2012

Oncology

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Purpose: Sorafenib improves survival in advanced hepatocellular carcinoma (HCC), but the demonstration of its efficacy and safety is limited to Child-Pugh A cirrhotic patients. The biweekly combination of gemcitabine and oxaliplatin (GEMOX) is safe and widely used in patients with advanced malignancies. We aimed to evaluate the feasibility of GEMOX in HCC patients with Child-Pugh B cirrhosis ineligible for sorafenib. Methods: The medical records of cirrhotic patients with advanced HCC receiving the GEMOX regimen between July 2006 and November 2011 were retrospectively reviewed. Treatment was repeated every 2 weeks until disease progression or unacceptable adverse effects occurred. The primary evaluation criterion was safety. Secondary evaluation criteria were the presence of muscle wasting (sarcopenia), response rate, progression-free survival and overall survival (OS). Results: Patients with Child-Pugh A (group A, n = 17) or Child-Pugh B cirrhosis (group B, n = 15) received a total of 169 cycles (median 4, range 1–16/patient). Eight patients in each group had sarcopenia. Common toxicities were thrombocytopenia (25 and 14 in groups A and B, respectively; p = 0.65) and peripheral neuropathy (44 and 54% in groups A and B, respectively; p = 1). Neither febrile neutropenia nor toxic death occurred. One patient in each group experienced grade 3 oesophageal varices bleeding. The response and disease control rates were 18% (95% CI 0–35.8) and 58.8% (95% CI 35.4–82.2) in group A, and 27% (95% CI 4.3–49.1) and 60.0% (95% CI 35.2–84.8) in group B. The median progression-free survival and OS did not differ between the two groups, but median OS was significantly shorter in sarcopenic patients. Conclusions: The GEMOX regimen appears feasible in HCC patients with Child-Pugh B cirrhosis and exerts anti-tumour activity. These data need to be confirmed in a prospective study.

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“…Identification of those with sarcopenia is important because sarcopenia is associated with elevated toxicity to chemotherapy (38,(58)(59)(60)(61)(62) . There is mounting evidence that sarcopenia increases the risk of toxicity to many drugs including Epirubicin (58) , Capecitabine (63) , Sunitinub (59) , Sorafinib (60,61) , 5-FU and leucovorin (62) . Table 3 summarises the available evidence for sarcopenia and dose-limiting toxicity in a variety of cancers and different chemotherapy drugs.…”

Section: Impact Of Sarcopenia On Tolerance To Cytotoxic Chemotherapymentioning

confidence: 99%

Cancer-associated malnutrition, cachexia and sarcopenia: the skeleton in the hospital closet 40 years later

et al. 2016

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An awareness of the importance of nutritional status in hospital settings began more than 40 years ago. Much has been learned since and has altered care. For the past 40 years several large studies have shown that cancer patients are amongst the most malnourished of all patient groups. Recently, the use of gold-standard methods of body composition assessment, including computed tomography, has facilitated the understanding of the true prevalence of cancer cachexia (CC). CC remains a devastating syndrome affecting 50-80 % of cancer patients and it is responsible for the death of at least 20 %. The aetiology is multifactorial and complex; driven by pro-inflammatory cytokines and specific tumour-derived factors, which initiate an energy-intensive acute phase protein response and drive the loss of skeletal muscle even in the presence of adequate food intake and insulin. The most clinically relevant phenotypic feature of CC is muscle loss (sarcopenia), as this relates to asthenia, fatigue, impaired physical function, reduced tolerance to treatments, impaired quality of life and reduced survival. Sarcopenia is present in 20-70 % depending on the tumour type. There is mounting evidence that sarcopenia increases the risk of toxicity to many chemotherapy drugs. However, identification of patients with muscle loss has become increasingly difficult as 40-60 % of cancer patients are overweight or obese, even in the setting of metastatic disease. Further challenges exist in trying to reverse CC and sarcopenia. Future clinical trials investigating dose reductions in sarcopenic patients and dose-escalating studies based on pre-treatment body composition assessment have the potential to alter cancer treatment paradigms.

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An exploratory study of body composition as a determinant of epirubicin pharmacokinetics and toxicity

Cited by 144 publications

References 27 publications

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

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

Feasibility of Gemcitabine plus Oxaliplatin in Advanced Hepatocellular Carcinoma Patients with Child-Pugh B Cirrhosis

Cancer-associated malnutrition, cachexia and sarcopenia: the skeleton in the hospital closet 40 years later

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