Cancer Pathophysiology and Cachexia Flashcards
(88 cards)
1
Q
When is cancer cachexia observed
A
in the later stages of cancer
2
Q
Give names and definition of cancer progerrsion stages
A
- Primary tumor: first tumor identified, classified according to size and invasion of surrounding tissues
- Secondary tumors: other tumors of the same histological origin as the primary, located nearby
- Regional lymph nodes: classified according to distance from primary tumor
- This is when tumour cells are evading in distance
- lymph node will pick up malignant cells as the protective mechanism of the organism in attempt to prevent further spread
- Metastasis: invasion of distal tissues and organs
3
Q
Effects of having CA of digestive tract
A
- obstruction
- dysphagia, nausea, vomiting- when CA is in the upper part of digestive tract
- anorexia, malabsorption- when CA is in the lower part of digestive tract
- anemia from occult losses- if tumour is the the wall of GI
- occult as it’s not apparent
- stool doesn’t become black
4
Q
Effects of having CA lung
A
obstruction of respiratory tract, shortness of breath
5
Q
Effects of having CA of bone
A
pain
6
Q
effects of hsving CA gynecologic
A
intestinal obstruction (if tumour is big enough), ascites (abnormal buildup of fluid in the abdomen), fertility
7
Q
Are biomarkers used for cancer diagnosis?
A
- some tumours secrete substances into blood e..g prostate tumour PSA (prostate specific antigen- good marker of tumour);
- not 100% specific but still accurate enough
- most tumours don’t have accurate biomarkers-> have to be detected with imaging techniques
8
Q
Name and explain Tumor imaging techniques:
A
- § MRI: magnetic resonance imaging
- § CT: computed tomography
- § PET: positron emission tomography
- provision of radioactive tracer to trace the increased activity of tumour cells
typically glucose tracer with Fluro4 as tumour cells consume a lot of glucose
- provision of radioactive tracer to trace the increased activity of tumour cells
- § Chest X-ray, ultrasound, mammogram, bone scans
9
Q
Name and describe invasive diagnosis techniques
A
- biopsy- all cancer that can be reachable from outside can be tested using biopsy e.g breast
- cytologic aspiration
- laparoscopy- camera is inserted with a catheter e.g. GI tract
10
Q
Where are each of these found?
- Carcinomas
- Sarcomas
- Lymphomas
- Gliomas
- Adenocarcinomas
- Leukemias
A
- Carcinomas- epithelial tissue
- Sarcomas- connective tissue
- Lymphomas- lymphatic tissue
- Gliomas- glial cells of CNS
- Adenocarcinomas- glands
- Leukemias- bone marrow
11
Q
What system is used for staging of cancer
A
- International System for Staging of Cancer
- For solid tumors: based on TNM system (Tumor, Node, Metastasis)
- Solid tumour cancers, like breast or prostate cancer, form lumps.
12
Q
What are the components of TNM system?
A
- Primary tumor (T: T1 to T4)
- based on size (T1- small, T4- large)
- lymph nodes (N: N0 to N3)
- Refers to the number and location of lymph nodes that contain cancer. The higher the number after the N, the more lymph nodes that contain cancer.
- metastasis (M: M0 or M1)
- M0: Cancer has not spread to other parts of the body.
M1: Cancer has spread to other parts of the body.
13
Q
What are the components of stage grouping?
A
14
Q
How are lymphomas classified?
A
Lymphomas are classified from I to IV
15
Q
What is the difference bewteen I(A) AND I(B) TNM subset?
A
I(B) is bigger
16
Q
Describe surgical removal as an anti-cancer treatment
A
- removal of of tumour and surrounding tissues
- can also be used even if it’s not gonna treat, but reduce the pain e.g. tumour that Metastasized to the bone
- first choice for curative Tx (may also be palliative, e.g. to alleviate pain)
- mostly for primary, local tumors (Stage I) and pre-cancerous lesions (various dermatological growths that are at an increased risk of developing into skin cancer)
- may be more or less invasive depending on site
17
Q
Curative nad adjuvant definitions
A
curative= can cure (destroy and eliminate the tumour) adjuvant= additional with other Rx
18
Q
Describe radiotherapy as a anti-cancer treatment
When is it prescribed?
Which kind of tumours is it used for?
What does the dose depend on
A
ionizing radiation altering DNA to control growth or kill malignant cells (continuously proliferating cells are most susceptible)
For curative Tx, or adjuvant with other treatment regimens
Radiotherapy is often used prior to surgery to reduce the size of the tumour before it gets removed
Targeted to tumors with relatively limited damage to surrounding tissues
Dose/fractionation vary according to type and size of tumors
19
Q
What are the side effects of radiotherapy?
A
- Side effects depend on site: head and neck: mucositis, dysgeusia, xerostomia, dysphagia, odynophagia,
- severe esophagitis-> hisk risk of malnutrition, may need tube feeding
- abdomen and pelvis: severe diarrhea, malabsorption, radiation enteritis ( severe inflammation of intestine; can last for a very long time)
20
Q
Describe chemotherpay as an anti-cancer treatment
How does it work?
How is it administered?
What are the side effect?
A
- Cytotoxic drugs that block DNA and RNA synthesis or cell division at different stages (next slide)
- Administered orally, IV infusion or intra-muscular injections, dose given in cycles
- Many systemic side effects (also affects healthy cells replicating rapidly)
- Cells that replicate reapidly: bone marrow cells (RBC, WBC), epithelial (including GI tract-> many GI tract problems), hair follicles-> hair loss
- Very harsh- >many side effects
21
Q
What are biological therapies used for?
A
to treat cancer itself, but mostly for progression or side effects
22
Q
Name and describe type of biological therapies
A
-
immunotherapy (IT): use body’s own immune system to eradicate cancer cells (e.g. synthesized interferons, interleukins, cytokines)
- infusion of cytokines to boost immune system
- controlling immune checkpoints
- re-infussion of immune factors
-
Biological response response modifiers (e.g. block angiogenesis)
- inhibitors of GH to block angiogenesis, prohibiting tumour to develop blood vessels, to shrink it and limit the growth
- Targeted therapy: monoclonal antibodies that deliver toxic molecules
23
Q
Biological therapy side effect
A
variable, systemic, but much less than the chemo ot radiotherapy
24
Q
What do we use Hematopoietic stem cell transplantation for?
Principle?
Side effects?
A
- For blood cancer
- to re-stimulate marrow production of blood cells
usually works well but there is a risk of graft vs. host disease- reaction of the host against the transplanted stem cells
25
What is the first line chemotherapy drug?
Class: Alkylating agents
– e.g. Cisplatin,c arboplatin
26
What are Chemotherapy agents: classes and examples
* Alkylating agents
* Cisplatin, carboplatin
* Indirect DNA agents
* 5-fluorouracil, gemcitabine
* Topoisomerase inhibitors - act upon the enzyme that polymerizes DNA sequence-\> stops DNA synthesis
* Irinotecan, topotecan
* Antitumor antibiotics
* Doxorubicin
* Antimitotics- stops cell division
* Vincristine, vinblastine, paclitaxel
27
What are the side effects that are common to all chemotherapy agents?
* Bone marrow suppression
* Anemia,neutropenia, thrombocytopenia
* N/V, stomatitis, diarrhea
* Alopecia (loss of hair)
* Anorexia
* Renal toxicity (cisplatin)
* Hepatotoxicity (5-FU)
* Cardiotoxicity (doxorubicin)
28
Biological and targeted therapy agents+ their side effects
29
Upper respiratory/di gestive tract
Tumor, surgery and radiotherapy impacts
comments?
Tumor impact- obstruciton, dysphagia
surgery impact- mastication and deglutition problems; can be transient or chrnoic
radiotherapy impacts- pain (5-7 d after Tx) a/dysgeusia, xerostomia
comments
30
Esophagus
Tumor impact
surgery impact
radiotherapy impacts
comments
Tumor impact- Obstruction, dysphagia, anorexia, anemia from occult losses
surgery impact- Early satiety, regurgitation, gastric stasis
radiotherapy impacts- Esophagitis, dysphagia, odynophagia (pain), fibrosis
comments
31
Stomach
Tumor, surgery and radiotherapy impacts
comments?
Tumor impact- Obstruction, anorexia, anemia, water and electrolyte losses
surgery impact- Early satiety, achlorydria, dumping syndrome, loss of intrinsic factor (helps b12 absorption-\> monitor for B12 deficiency )
radiotherapy impacts- Fibrosis, ulcers
comments
Enteral nutrition by jejunostomia after Tx; tube is entered directly into the small intestine to bypass the stomach
32
Pancreas, biliary tract
Tumor, surgery and radiotherapy impacts
comments?
Tumor impact- Weight loss, abdominal pain, anorexia, nausea, malabsorption, secondary diabetes (due to pancreatitis)
surgery impact
radiotherapy impacts
comments- Enteral nutrition by jejunostomia after Tx; tube is entered directly into the small intestine to bypass the stomach
33
Liver
Tumor, surgery and radiotherapy impacts
comments?
primary tumours in the liver are rare; metastasis are common
colon cancer is associated with liver metastasis
Tumor impact- Weight loss is frequent, anorexia
surgery impact- Partial hepatectomy: no specific effect; as the remainder of the liver can sustain normal function; better prognosis that many other surgeries
radiotherapy impacts- Anorexia, nausea, hepatomegaly, risk of hepatitis if high dose
comments:
Post-op nutritional support important, capacity to regenerate
34
Small intestine, colon, rectum
Tumor, surgery and radiotherapy impacts
comments?
Tumor impact- Obstruction, anemia from occult losses, malabsorption, steatorrhea
surgery impact- Ileal resection: Decreased B12, Ca, Mg, lipo vit. bile salt absorption,; Colectomy: water and electrolyte losses
radiotherapy impacts-
Radiation enteritis: cramps, diarrhea, N&V, malabsoption (Ca, Mg, Fe, B12), steatorrhea; fistula, perforation
comments:
Concomittant chemo- Tx is aggravating; severity depends on volume irradiated, TPN may by indicated
35
Breast
Tumor, surgery and radiotherapy impacts
comments?
Tumor impact- weight gain with some forms due to increased secretion of growth factors by the tumour
surgery impact- n/a
radiotherapy impacts- Possible impact on esophagus due to the proximal location
comments- n/a
36
Lung
Tumor, surgery and radiotherapy impacts
comments?
Tumor impact- weight loss is frequnet due to tumour or malnutrition
surgery impact- n/a
radiotherapy impacts- Possible impact on esophagus due to the proximal location
comments- n/a
37
Gynecological organs
Tumor, surgery and radiotherapy impacts
comments?
Tumor impact-
Intest. obstruction (by pressure), enteropathy, ascites
surgery impact- n/a
radiotherapy impacts- Possible impact on intestinal mucosa
comments:
Diuretics or sodium restriction are not relevant
38
What is achloridya
achlorydia- decreased HCL secretion-\> decreased digestion and absorption
39
What is dumping syndrome?
Dumping syndrome is a condition that can develop after surgery to remove all or part of your stomach Also called rapid gastric emptying, dumping syndrome occurs when food, especially sugar, moves from your stomach into your small bowel too quickly, creating osmotic effect
40
What is a GI fistula?
A gastrointestinal fistula (GIF) is an abnormal opening in your digestive tract that causes gastric fluids to seep through the lining of your stomach or intestines. This can result in infection when these fluids leak into your skin or other organs.
41
Bone metastases
Tumour impact
Surgery impact
Radiotherapy impact
Comments
* Tumour impact- Pain (anorexia)
* Surgery impact
* Radiotherapy impact
* Comments- Constipation secondary to analgesia
42
Defintion of cancer cachexia
A complex metabolic syndrome associated with underlying illness and characterized by loss of muscle with or without loss of fat mass. The prominent clinical feature is weight loss...
many conditions combined together;
doesn’t happen by itself
mostly muscle loss; but most often both
43
What is refractory cachexia
Cachexia observed surign the last month of live
When nothing can be done
44
How do chronic diseases such as cancer lead to weight loss, weakness and fatigue
45
What are the consequences of cachexia and Muscle wasting that predict poor cancer-associated outcomes:
* ↑ fatigue
* ↑treatment-induced toxicity: toxicity is reached at a lower dose when muscle mass is lower-\> chemo has to be stopped before it is completed
* ↓host response to tumor
* ↓ performance status
* ↓ survival
46
What is sarcopenic obesuty, it's prevalence and consequences
Sarcopenic-obesity: obesity with depleted muscle mass
* ≈15% of patients with lung or gastro-intestinal tumors
* worse outcomes than obese or sarcopenic patients
47
How is muslce mass and risk of death connected?
* exponential relationship between muscle mass and hazard ratio for death
* sufficient evidence that below certain level of mascularity the risk of death increases exponentialy
48
what is the overall prevalence of cancer cachexia and how does it differ with various cancer types?
* Overall prevalence: 50-80%
* Cachexia occurs more frequently in certain types of cancer:
* Upper gastro-intestinal cancer : 80%
* upper gastric and pancreatic: 83-87%
* Lung cancer: ≅ 60%
* seen less in breast and prostate as these are not associated with weight loss; at least until advanced stages of cancer
49
Cachexia pathophysiology
There are 2 factors of pathophysiology of cachexia:
1) metabolic change (hypercatabolsim & hyperanabolsim)
* hyper-catabolism- more protein catabolism than anabolism-\> muscle loss and negative nitrogen balance
* hypo-anabolism - lower response to anabolic stimulus e.g lower response to insulin, to amino acids-\> reduced anabolic response-\> weight and muscle loss
* these changes can be induced by inflammation or catabolic factors that are released by tumours or induced by the tumour presence
and (2) reduced food intake
* reduced food intake is already seen in patients with cancer in upper GI./head and neck region (secondary to dysphagia)
* anorexia can be induced by inflammation and by factors secreted by tumours-\> **primary** anorexia
* **secondary** anorexia is due to the cancer treatment (chemo or radio)
50
Starvation vs cachexia
* end result of starvation (loss of muscle and fat tissue) will look similar to the end result of cachexia, but trajectory is different
* *cachexia progresses faster**
* **Protein synthesis** and **Protein degradation** are lower in starvation to protect muscle; lower protein turnover
* In cachexia, the Protein synthesis is either reduced or maintained; Protein degradation is increased
* Protein synthesis depends on the organ.Iif we look at muscle-\> decreased or maintained; liver-\> increased
* **cachexia: rapid protein turnover which contributes to increased REE**
* Lean mass loss is greater in cachexia, including organ mass
* Caloric intake is decreased more in starvation
* TEE decreases less in cachexia
* biggest difference; REE increases in chachxia-\> hypermetabolism
* In cachexia response to insulin is less-\> insulin resistance
* Corisol is unchaged in stravation; increased in cachexia, contributing to stress reponse
51
What are the stages of cachexia?
52
What are the components of fat-free mass that are lost during weigth loss
mainly from skeletal muscle
(visceral proteins are better preserved)
53
How do the rates of tissue loss change over the disease progression?
losses are much faster when it’s closer to death
54
Risk of reduced survival as a function of BMI and weight loss
* someone with High BMI and smaller weight loss wil survive longer than someone with lower BMI with the same weight loss
* higher the weight loss, the less the survival time; true for all BMI categories
* key message: beneficial to have higher BMI during cancer cachexia + increased tolerance to treatment
we don’t know whatsup with bmi 30+le
55
How do concentration or responsiveness in anabolic and catabolic factors change in cachexia?
_̄ Decreased concentration or responsiveness in anabolic factors:_
* Insulin (levles are normal but the response is lower)
* IGF-1
* Growth hormone
* Thyroid hormone Testosterone
_Increased concentration of catabolic factors:_
* Glucagon
* Cortisol
* Pro-inflammatory cytokines
* Eicosanoids
* Tumor-derived factors
56
What is an accute phase response?
Coordinated adaptations of the body to limit and clear the tissue damage caused by hydrolases released from inflammatory, injured or malignant cells.
57
What defines whether the acute phase proteins are positive or negative?
Hepatic synthesis of acute-phase proteins:
their plasma concentrations **increase** (positive) or **decrease** (negative) by \>25%
58
Name positive and negative acute phase proteins?
Positive
* Complement system
* Coagulation and fibrinolytic system
* Antiproteases
* Participants in inflammatory responses
* Others: C-reactive protein, fibronectin, ferritin, ceruloplasmin, haptoglobin
Negative
* Albumin
* Transferrin
* Transthyretin
* Thyroxin-binding globulin
* IGF-1
* Factor XII
* Alpha-fetoprotein
59
What usuaully happens to transport proteins during infalmmation?
transport protein levels usually decrease with inflammation
60
How do albumin ciruclation and synthesis levels change in inflammation?
albumin levels decrease in inflammation, but synthesis doesn’t increase in cancer cachexia, but levels are decreased due to extra-vascularization of albumin (albumin escapes vascualr walls to accumulate in tissues-\> fluid accumulation)
61
How is acute-phase response modulated?
The acute-phase response is modulated by cytokines
§ Cytokines are produced by the tumor and/or the host:
§ Secreted from immunocompetent cells: lymphocytes, macrophages
§ They act locally (paracrine and autocrine) and systemically (endocrine) as they are released into the circulation
62
What are the pro-inflammatiry cytokines that have been found to be at high levels durign cancer
High serum levels of these cytokines have been found in some, but not all types of cancer:
– Tumor-necrosis factor alpha (TNF-α)
– Interleukins 1 and 6 (IL-1, IL-6)
– Interferon gamma (IFN-γ)
– Leukemia inhibitory factor (LIF)
63
Apart from modulating acut-phase response, what are the other effects of cytokines?
* Decrease appetite and food intake, resulting from both central and peripheral elements
* Decrease GI functions: Decreasegastric emptying (contributes to nausea and lack of appetite), intestine mobility
* Decrease blood flow
* Inhibit lipoprotein lipase (LPL)
* Inhibit growth hormone and IGF-1 signaling
* Induce insulin resistance (IL-6)
64
Host-tumor interactions
* liver needs AA for this
* these AA come form muscles, if there’s lack of substrate from the diet
* using AA for acute protein synthesis is not a 100% efficient recycling process-\> there will be losses as there are specific AA that are required more than other (thus the not required ones will be lost)
* there will a negative nitrogen balance
Muslce
increased proteolysis-\> increased AA release into the circulation
65
Energy expenditure components: cachectic individuals vs sedentary to moderately active individuals
Cachexia
increased in REE -\> hyper-metabolism
decrease of PA -\> reduced to minimal activity in advanced stages
very high REE as a proportion of TEE
TEE is less than in a healthy individual
66
How are lipids affected in cachexia?
Mobilization of lipids and increased turnover of fatty acids
* Increased lipolysis, FFA, VLDL
* Decreased LPL activity-\> less storage of dietary fat
* Hypertriglyceridemia
67
How is glucose metabolsim affected in cachexia?
* Glucose is the preferred fuel for tumors
* Tumors use anaerobic glycolysis-\> produce lactate -\> Cori cycle (uses ATP), and produces less ATP than beta-oxidation
* Increased gluconeogenesis -\> increased proteolysis (muscle)
* Insulin resistance
68
How is protein metabolsim affected in cachexia?
* Negative N balance
* ↑ protein turnover
* ↑ or ↔ muscle proteolysis: provides AA for GNG, acute-phase protein synthesis and tumor growth
* may not be super accurate as it is hard to measure proteolysis rates in humans
* ↓ or ↔ in muscle protein synthesis; because AA are used for gluconeogenesis and tumour growth instead of using those for muscle synthesis
* ↑ hepatic protein synthesis (APPs)
69
What are the pathways of proteolysis?
what is the relative importance of each?
1. Lysosomal (caspases)
2. Ca++-dependent (calpains)
* These 2 are responsible for 15-20% of total muscle protein degradation
3. ATP-dependent ubiquitin-proteasome pathway
* The most important in skeletal muscle proteolysis in many wasting conditions, including cancer cachexia
* requires energy
70
Describe Ubiquitin-proteasome system
* protein gets tagged with ubiquitin which will signal that this protein needs to be degraded
* end result: small peptides and ubiquitin are released; ubiquitin will be recycled
* the last step: ligase (ubiquitinE3 ligase) is an enzyme that will link ubiquitin to the protein- this step is the step that is the most highly regulated by the known genes- atrogenes
* control action and expression of ligase
* the more of this genes is expressed, the more tagging and proteolysis occurs
* these genes are also regulate by pro-inflammatory cytokines - TNF-a, IL-1 and maybe IFN-gamma-\> inflammation can control gene expression that regulates the activity of ligase
* this is how inflammation results in proteolysis
71
Integrated metabolic changes on the level of muscle, liver and adipose tissue
tumour is consuming a lot of glucose-\> lactate is produced
lactate will be reconverted to glucose through Cori cycle. This cycle is not dependent on inflammation
Tumour will secrete pro-inflammatory cytokines/ tumour factors. they will stimulate proteolysis in the muscle
the muscle will release AA that can be taken by the liver to produce glucose through gluconeogenesis
gluconeogenesis and proteolysis via ubiquitin pathway require ATP-\> higher energy needs
cytokines will also stimulate lipolysis in the adipose tissue (Also ATP dependent) -\> FFA are released into circulation-\> go to the liver for energy
72
3 process that increase energy requirement and result in hyper-metabolism
- lipolysis
- proteolysis
- gluconeogenesis
73
Anoriexia is Associated with \_\_% cases of cachexia
Anoriexia is Associated with \>50% cases of cachexia
74
What are the potential causes of anorexia in cancer?
§ Obstruction of the GI tract
§ Malabsorption
§ Pain
§ Depression/anxiety
§ Constipation
§ Radio- and chemo-therapy
§ Inflammation
§ Many patients with no obvious clinical reason
75
Describe Regulation of appetite & food intake
and how is it affected in cachexia
* Controlled by a complex of hormones and neuropeptides in the hypothalamus
* Homeostasis: energy repletion or depletion
* In cachexia: dysregulation of homeostasis by persistent activation of POMC (pro-opiomelacortin) neurons.
* In cachexia: dysregulation of homeostasis by persistent activation of POMC (pro-opiomelacortin) neurons leading to lower appetite, separate from impact of inflammation on appetite and increased energy expenditure
76
What may cause early satiety in cancer cachexia?
Results from:
§ Reduced GI motility
§ gastric emptying time
§ May be caused by autonomic dysfunction and opioid analgesics
77
What are direct consequences of antineoplastic therapies? When else might this conditions occur
Nausea and chemosensory abnormalities, are direct consequences of antineoplastic therapies, but also very frequent in untreated patients; thus can be caused by the cancer itself
78
What are the possible causes of nausea?
§ Side effect of drugs
§ Abdominal disease, intracranial metastases, metabolic derangements, GI stasis
79
What are the potential causes of Distorsion of taste and smell
Includes: hypersensitivity to odors and flavors, persistent bad tastes, phantom smells, food aversions
* Apart from treatment, may result from chronic nutritional deficiencies
some nutrients also change taste and smell, such as Vit A and zinc-\> have to make sure that there’s no nutritional deficiencies
80
What are the cut-offs for diagnosis of cachexia
Which methods are mostly used and why?
1. Weight loss \>5% over past 6 months (in absence of simple starvation)
OR
2. BMI \<20 kg/m2 and any degree of weight loss \>2%
OR
3. Appendicular muscle mass consistent with sarcopenia (\<7.26 kg/m2 in men; \<5.45 kg/m2 in women)
and any degree of weight loss \>2%
for number 3 dexa scan is used, but that would be available only in clinical conditions, thus we usually rely on the first 2 methods
81
Additional assessment to diagnosis to define severity and phenotype and target appropriate treatment:
* Anorexia or reduced food intake
* Questionnaires or \<70% of usual food intake
* Catabolic drive
* hard to measure-\> so we use surrogate measure **CRP** that doesn’t measure catabolism, but indicates inflammation
high/acute inflammation can lead to acute catabolism
* Muscle mass and strength
* Functional and psychosocial effects
* questionnaires
82
Are there drugs for cachexia?
No widely approved drugs with demonstrated efficacy are currently available, many require further clinical trial corroboration.
83
Describe Agents to increase appetite as a way of treating cachexia
* Progestational agents that are usually used for contraception (megestrol acetate): ↑ appetite and weight gain but not lean mass. Serious side effects: oedema, thromboembolism.
* Corticosteroids (anti-inflammatory drugs, but can also increase appetite): transient increase in appetite and well-being. Side effects: insulin resistance, muscle wasting, osteopenia. Should be used for restricted periods (1-3 weeks).
* Cannabicoids: dronabinol may have potential but inconsistent evidence to (increase appetite and control pain)
84
Describe Therapeutic agents in cancer cachexia for symptom management
§ Antiemetics- to reduce vomiting and nausea
§ Antidepressants- can lead to weight gain (good)
§ Corticosteroids
§ Anti GI motility agents- to treat diarrhea
§ Narcotics and other analgesics- to reduce pain, but associated with constipation
85
Describe how hormones may be used for cachexia treatment
* § Growth hormone +/- IGF-1: no proven benefits
* § Melatonin: no proven benefits
* § Anabolic agents and steroids: adverse effects
86
Describe how Anti-inflammatory agents, cytokine-directed may be used for cachexia treatment
§ **Thalidomide**: inhibits TNF-α, may attenuate weight loss
§ **Pentoxifylline**: inhibits TNF-α, no proven benefits
§ **Proteasome** inhibitors: no proven benefits
87
Pharmacologic agents under investigation to treat cachexia
Selective androgen receptor modulators (SARMs, Enobosarm):
* increased lean body mass and muscle function in elderly patients
* Phase II RCT in NSCLC patients treated with chemotherapy (POWER trial): ↑ LBM, muscle power, +/- stair climbing.
Ghrelin receptor agonist (Anamorelin):
* 2 phase III trials in NSCLC with cachexia (ROMANA 1&2) completed: significant increase in appetite, weight gain, lean mass and quality of life but not handgrip strength (Temel et al. Lancet Oncol 2016)
88
What might need to be added to patient's regimen when giving analgesics?
analgesics -\> lead to constipation-\> provide sufficient fluid intake and fiber; if severe-\> laxative
