Table Of ContentPOCKET BOOKS FOR CANCER SUPPORTIVE CARE
Cancer Cachexia
Egidio Del Fabbro
Akio Inui
Florian Strasser
Cancer Cachexia
Cancer Cachexia
Egidio Del Fabbro
Virginia Commonwealth University
Richmond, Virginia
USA
Akio Inui
Kagoshima University Graduate School of Medical and Dental Sciences
Kagoshima, Japan
Florian Strasser
Cantonal Hospital
St Gallen, Switzerland
Contributors
David Blum
Cantonal Hospital
St Gallen, Switzerland
Hajime Suzuki
Kagoshima University Graduate School of Medical and Dental Sciences
Kagoshima, Japan
Part of the Springer Healthcare Cancer Supportive Care Series
Published by Springer Healthcare Ltd, 236 Gray’s Inn Road, London, WC1X 8HB, UK.
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Reprinted in 2014
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ISBN 978-1-910315-06-4
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Contents
Author biographies vii
1 Overview of cancer cachexia 1
Introduction 1
Epidemiology 3
Comorbidities 4
Disease burden 4
References 4
2 Pathophysiology 7
Introduction 7
Hormones and mediators 7
Negative nitrogen balance 13
Myostatin 14
Insulin-like growth factor-1 14
Oxidative stress 16
Anabolic hormones 16
Effects on antineoplastic therapy 17
References 20
3 Impact of cancer cachexia 25
Primary cachexia 27
Secondary cachexia 28
Quality of life 34
Impact of weight loss on survival 37
References 38
4 Patient assessment 41
Identification of patients with cachexia in clinical practice 41
References 48
V
vi • CONTENTS
5 Managing cancer cachexia 51
Treatment goals in current standard of care 51
Pharmacological treatments 52
Non-pharmacological treatments 55
Managing side effects 58
Cancer cachexia in special populations 60
References 69
6 Emerging treatments, current challenges, and
future directions 73
Emerging treatments 73
Nutritional counseling 76
Multimodal treatment 77
References 80
Author biographies
David Blum MD obtained his medical degree from the University of Zürich
in 2002 and received the Swiss board certification of Internal Medicine
in 2009 and Medical Oncology in 2011. He was a resident doctor and
research fellow (EPCRC) at Oncology DIM Kantonsspital St. Gallen in
Switzerland and is currently undergoing EURO IMPACT - Marie Curie
PhD training fellow at European Palliative Research Center NTNU in
Trondheim, Norway. His main research interests include symptom assess-
ment and the role of computer assistance, cancer cachexia, physical
activity, end of life care, and integration of oncology and palliative care.
Dr. Egidio Del Fabbro (MD) obtained his medical degree from the
University of the Witwatersrand in South Africa. He completed his
residency in Internal Medicine at Barnes-Jewish Hospital, Washington
University. He was co-founder of the Cachexia Clinic at MD Anderson
Cancer Center and is currently Director of the Palliative Care Program
at Virginia Commonwealth University. Dr. Del Fabbro’s research interest
lies in developing clinical trials for cancer-related cachexia and fatigue.
He is the senior editor for the textbook, Nutrition and the Cancer Patient.
Professor Akio Inui (MD, PhD) is the Chairman of the department of
Psychosomatic Internal Medicine of Kagoshima University Graduate School
of Medical and Dental Sciences, Kagoshima, Japan. Professor Inui completed
his MD and PhD degrees at Kobe University, Japan. Professor Inui is rec-
ognized for his studies in elucidating the role of gut–brain peptides in the
regulation of gastrointestinal motility, feeding, and body weight, and the
identification of the ghrelin–neuropeptide Y pathway from stomach to brain
in the pathogenesis of obesity and cachexia. Professor Inui has authored
more than 250 peer-reviewed publications. His efforts are now focused on
translational research on peptides that bridges the gap between basic and
clinical disciplines for better understanding and management of human
behavioral disorders, including obesity, cancer cachexia, and eating disorders.
VII
viii • AUTHOR BIOGRAPHIES
Dr Florian Strasser is medical doctor with board certification in internal
medicine, medical oncology, and palliative medicine. His clinical and
research activities focus involve integrated oncology and palliative care.
His focus is on the development of clinical models to integrate oncology
and palliative care in the primary and secondary sector. His work is also
affiliated with international organizations such as the European Society
of Medical Oncology (ESMO), Multinational Association of Supportive
Care and Cancer (MASCC), European Association of Palliative Care
(EAPC), American Society of Clinical Oncology (ASCO), and International
Association of Hospice and Palliative Medicine (IAHPC). In addition, his
research is in oncological rehabilitation with a focus on cachexia and
nutrition. He is the first oncologist in Switzerland with a Venia Legendi
(Privatdozent) on specialist palliative care, awarded from the University
of Bern.
Dr. Hajime Suzuki (DDS) belongs to the department of Psychosomatic
Internal Medicine of Kagoshima University Graduate School of Medical
and Dental Sciences, Kagoshima, Japan. He completed Doctor of Dental
Surgery (DDS) degrees at Kagoshima University. His research interest
lies in the field of cancer cachexia, obesity, and related metabolic syn-
dromes, with the specific focus on the neuroendocrine and metabolic
effects of feeding regulatory peptides in the coordinated regulation of
energy balance. His research also focuses on the role of complementary
and alternative medicine in the palliative care of patients with cancer.
Chapter 1
Overview of cancer cachexia
Introduction
Cachexia (uncontrolled, unintentional weight loss, and muscle wasting) is
common in patients with advanced cancer and can have a profound impact
on quality of life, symptom burden, and a patient’s sense of dignity. It is a
very serious complication, as weight loss during cancer treatment is associ-
ated with more chemotherapy-related side effects, fewer completed cycles
of chemotherapy, and decreased survival rates [1,2]. Although cachexia
is often under-recognized by health care providers, there is a growing
awareness of the positive impact of supportive care measures [3] and
development of promising novel pharmaceutical agents for cachexia. While
there has been great progress in understanding the underlying biological
mechanisms, health care providers must also recognize the psychosocial
and biomedical impact cachexia can have. The high prevalence of cachexia
among cancer patients suggests that health care providers will increasingly
be expected to carefully assess and manage patients with this condition.
There is research to suggest that patients and their families view
poor appetite as the most distressing symptom they encounter during
cancer treatment [4]. Fortunately, the body of evidence focusing on
the effective management of cachexia (with both pharmacological and
non-pharmacological intervention) is growing and has raised awareness
of the condition. In fact, if physicians do not proactively address concerns
regarding nutrition and weight loss in cancer, they might be perceived
by patients and their families as guilty of ‘selective neglect.’
(cid:2)SpringerHealthcare2012 1
E.DelFabbroetal.,CancerCachexia,
DOI10.1007/978-1-910315-07-1_1
2 • CanCer CaChexia
Definition of cancer cachexia
In order to aid clinical trial design, develop practice guidelines, and
establish routine clinical management of cachexia, a consensus on
a framework for the definition and classification of cancer cachexia
was reached in 2011 [5]. According to Fearon et al, cancer cachexia is
defined as “a multifactorial syndrome characterized by an ongoing loss
of skeletal muscle mass (with or without loss of fat mass) that cannot
be fully reversed by conventional nutritional support and leads to pro-
gressive functional impairment” [5]. The pathophysiology is driven by a
variable combination of reduced food intake and abnormal metabolism
leading to a negative protein and energy balance.
A diagnosis of cachexia can be made in patients with total body weight
loss that is >5% over the previous 6 months (in the absence of starvation)
or weight loss that is >2% in a patient with a body mass index (BMI) of
<20 kg/m2 [6]. In addition, an appendicular skeletal muscle index consist-
ent with sarcopenia (males <7.26 kg/m2; females <5.45 kg/m2) and any
degree of weight loss that is >2% of total body weight is also consistent
with cachexia [6]. However, routine measurement of the skeletal muscle
index may not be feasible in the outpatient clinic.
The clinical cachexia spectrum is divided into three stages of clinical
relevance: pre-cachexia, cachexia, and refractory cachexia (Figure 1.1)
[5]. Patients with pre-cachexia may have early clinical features such as
poor appetite and impaired glucose tolerance that precede substantial
weight loss, while patients with refractory cachexia are characterized
Clinical continuum of cancer cachexia
Pre-cachexia Cachexia Refractory cachexia
Normal Death
Weight loss ≥5% >5% weight loss or Low performance
Anorexia If BMI <20+, >2% score
Metabolic change weight loss or <3 months expected
Reduced food survival
intake/systemic Cancer procatabolic
inflammation and not responsive to
treatment
Figure 1.1 Clinical continuum of cancer cachexia. BMI, body mass index (kg/m2). Adapted with
permission from Fearon et al 2011 [5].
