Transcript Drugs which may impair intestinal folate absorption

Nutritional Management of the
Cancer Patient
Joel Mason, M.D.
Associate Professor of Medicine and
Nutrition, Divisions of Gastroenterology and
Clinical Nutrition, Tufts University
topics of discussion

The extent of protein-calorie malnutrition (PCM) among
cancer pts

The clinical ramifications of PCM

How to detect clinically significant levels of PCM

Is it worthwhile addressing the issue in the cancer
patient and, if so, how?
Survey of 477 cancer patients: prevalence of
protein-calorie malnutrition(PCM)
site
stomach
esophagus
pancreas
colorectal
head & neck
lung
breast
ovary
prostate
uterus
% malnourished (>10 loss of UBW)
89%
78 odds ratio of PCM with cancers
58 of digestive tract or head & neck
36 = 3.2 (C.I. 2.0-5.2)
52
31
10
25
17
31
overall = 30%
Ann Oncol 2007
Adverse clinical consequences of weight loss
in cancer: case-control and prospective cohort
trials

outcome
diminished survival
study
Ann Surg. 2004; 240(4): 719
Am J Med 1980;69:491
Eur J Cancer 1998;34:503
Cancer 1999;86:519
Hepatogastro 1999;46:103

decreased response to chemoRx
and XRT
Arch Otolaryngol Head Neck Surg
1998;124:871–875
Eur J Cancer 1998;34:503

increased perioperative morbidity
J Surg Oncol 1992;49:163

worse quality of life
Eur J Cancer 1998;34:503
Adverse clinical consequences of weight loss
in cancer: case-control and prospective cohort
trials

outcome
diminished survival
study
Ann Surg. 2004; 240(4): 719
Am J Med 1980;69:491
Eur J Cancer 1998;34:503
Cancer 1999;86:519
Hepatogastro 1999;46:103

decreased response to chemoRx
and XRT
Arch Otolaryngol Head Neck Surg
1998;124:871–875
Eur J Cancer 1998;34:503

increased perioperative morbidity
J Surg Oncol 1992;49:163

worse quality of life
Eur J Cancer 1998;34:503
Factors that contribute to the development of
protein-calorie malnutrition in the cancer patient

Alterations in metabolism


increases in protein catabolism
inefficiency in energy consumption/increases in overall caloric expenditure
Factors that contribute to the development of
protein-calorie malnutrition in the cancer patient

Alterations in metabolism



Alterations in physiology



increases in protein catabolism
inefficiency in energy consumption/increases in overall caloric expenditure
malabsorption/maldigestion due to tumor or to therapy
constipation/gastrointestinal dysmotility due to surgical ablation of autonomic innervation of gut or to
narcotics and sedatives
Insufficient dietary intake

suppression of appetite
o
o
o



mediated by cytokines, other humoral factors
mediated by emotional depression
mediated by loss of taste sensation (neural destruction, drug effects, paraneoplastic syndrome)
learned aversion to eating due to adverse symptoms
nausea, vomiting, other symptoms due to surgery, radiation, or chemotherapy
Physical impairment of deglutition





effects on chewing or swallowing mechanisms
reduction in saliva production (tumor invasion, effects due to surgery, radiation, or drugs)
mass effect of tumor
radiation- or chemotherapy-induced mucositis
surgical interruption of swallowing mechanism
normal
body protein pool
catabolism
synthesis
amino acid pool
gluconeogenesis + urea
(~250 gms
protein/day)
dietary replacement
Wasting in cancer
body protein pool
catabolism
synthesis
(up to ~700 gms
protein/day)
amino acid pool
gluconeogenesis + urea
dietary replacement
Protein-calorie malnutrition: a body compartment
perspective
Simple starvation
Fat mass
+++
somatic lean mass
+
visceral lean mass
+/-
Wasting in cancer
+++
+++
+/++
Relationship Between Body Weight Loss
and Loss of Total Body Protein
Weight loss (%) 95% Confidence limits for
protein loss (%) in 100
patients
5
11.2-16.8
10
15.2-20.8
15
19.2-24.8
20
23.0-29.0
25
26.8-33.2
>10% unintentional loss of usual body weight: a
convenient and suitable means of defining substantial
malnutrition

Associated with a 15-20% loss of body cell
mass

Beyond this threshold, physiologic functions
are adversely affected

Beyond this threshold, clinical outcomes are
also significantly worse
Men
Women
Height
(cm)
Ideal creatinine
(mg)
height
ideal creatinine
157.5
1,288
147.3
830
160.0
1,325
149.9
851
162.6
1,359
152.4
875
165.1
1,386
154.9
900
167.6
1,426
157.9
925
170.2
1,467
160.0
949
172.7
1,513
162.6
977
175.3
1,555
165.1
1,006
177.8
1,596
167.6
1,044
180.3
1,642
170.2
1,076
182.9
1,691
172.7
1,109
185.4
1,739
175.3
1,141
188.0
1,785
177.8
1,174
190.5
1,831
180.3
1,206
193.0
1,891
182.9
1,240
Creatinine-height Index: a
measure of skeletal muscle
mass and a means of
detecting PCM
•calculation: 24 hour urinary
creatinine/ideal value for height and
gender
•values <80% of ideal = moderateto-severe PCM
JPEN J Parenter Enteral Nutr 1977;1:11–22
Alterations in Energy and Protein Metabolism
During Wasting in Cancer: Mediators
1.
Cytokines: immune cells activated by neoplasm: TNF-, interleukin-1, 2 and 6,
gamma-interferon


2.
Proteolysis-inducing factor*
•
•
3.
 peripheral lipolysis and hepatic lipogenesis
 energy expenditure, increased proteolysis
glycoprotein produced by the cancer cells, found in urine of cachectic cancer pts but
not those w/o cachexia, and not those whose cachexia is due to other diseases
? reproducibilty
Lipid-mobilizing factor#
•
•
•
 peripheral lipolysis (release of fatty acids and glycerol)
peripheral lipogenesis
produced both by neoplastic cells, which can also stimulate its expression in adipocytes
*Nature 1996;379:739–742
*Br J Cancer 2001;84: 1599-1601
#Proc Natl Acad Sci USA 2004;101: 2500-05
How does one determine whether
a given patient warrants intensive
nutrition support?
How does one determine whether
a given patient warrants intensive
nutrition support?
*using whatever practical means is necessary to adequately
meet the nutritional needs of the patient
Under what conditions does ‘aggressive nutrition support’
benefit the cancer patient: an evidence-based approach



The malnourished patient about to undergo major
surgery
A patient (malnourished or not) about to undergo bone
marrow transplantation
A patient about to undergo XRT or chemotherapy*
*improved quality of life proven but not a decrease in morbidity or mortality
Cumulative Incidence of Complications Within 30
Days After Randomization: VA Cooperative Study
NONE
MILD
MODSEVERE
12.5%
23.6
20
19.4
5.3
42.9
relative risk
0.53
1.03
0.12*
p value
0.20
1.00
0.03
95% confidence int.
0.22-1.28
0.63-1.69
0.02-0.91
non-infectious
complications
TPN group
control group
Adapted from: New Engl J Med 1991;325:525
A randomized clinical trial of perioperative TPN in
malnourished patients with GI cancers undergoing
curative resection, n=90
non-infectious cx’s
TPN*
12%
Control
34%
mortality
0%
11%
*10 days of pre-op tpn/9 days of postop tpn versus ad lib pre-op/1000 kcal/d + 85 g protein/d
postop
p = 0.05
J Parent Ent Nutr 2000;24: 7
p = 0.02
Similarly, in a RCT of 124 pts undergoing curative resection hepatocellular CA, the group
receiving pre- + postop TPN had a RR of overall cx’s of 0.66 (CI=0.45-0.96), and a RR of
infectious cx’s of 0.57 (CI=0.34-0.96). NEJM 1994;331:1547
Does use of TPN (vs. no nutritional support) in ill
patients benefit their hospital course: a meta-analysis of
26 randomized controlled trials
major complications
All subjects
Malnourished
mortality
RR = 0.84 (0.64-1.09)
1.03 (0.81-1.31)
0.52 (0.30-0.91)**
1.13 (0.75-1.71)
**TPN possesses significant benefit
J.A.M.A 1998;280:2013
Enteral vs. parenteral nutrition in malnourished
cancer patients: a multicenter trial
317 malnourished patients about to undergo curative resection for
GI cancers at 10 centers, randomized to isocaloric and isonitrogenous
regimens, to begin within 24 hours after surgery
enteral
parenteral
overall postop cx’s
infectious cx’s
34%, RR=0.7, p<0.01
16%, RR=0.59, p<0.02
49
27
postop LOS
13.4 d, p<0.01
15.0
Lancet 2001;358:1487
‘Aggressive’ nutritional support in cancer
patients: additional features
1.
Initiating nutritional support prior to surgery (typically >7 days) is superior to
starting postoperatively. If the latter is pursued, nutritional support must begin
within 24 hours after surgery to demonstrate a benefit.
2.
Studies with stable isotopic labelling of amino acids demonstrate that
significant and substantial improvements of protein synthesis are achieved in
patients with cancer
3.
Studies in animals show tumor growth can be stimulated by provision of
nutrition (and human studies confirm increased proliferation in the tumor) but
this should not present a problem if patient is undergoing curative Rx, and
may even present an advantage
Characteristics of ‘immunomodulatory’ enteral
formulas (Impact, Immun-Aid)

functions
 delivers nutritional requirements
 modulate immune system (‘neutraceutical’)

nutritional ingredients present in pharmacologic
quantitites




arginine
Ω-3 fatty acids
glutamine
nucleotides
*Impact Advanced Recovery is the only product that can be used orally
A meta-analysis of malnourished cancer
patients undergoing elective surgery
9 randomized controlled trials, conducted 1992-1999, comparing
preop use of IEFs to standard enteral formulas
mortality
infections
hospital stay
0.99 (0.42-2.34)
0.53 (0.42-0.68)*
-3.4d (-4.6--2.2)*
JAMA 2001;286:944
In a large RCT (n=305), pre-operative administration with 1 L/day for 5 days prior to surgery was as
effective in reducing postop infections and LOS as same regimen given for additional 9 days after surgery.
Both were far superior to standard IV therapy. Conducted in pts with <10% weight loss! Gastroenterology
2002; 122:763
Summary

Protein-calorie malnutrition is common amongst cancer patients and is
associated with poorer outcomes. GI and head & neck cancers have the highest
prevalence

The cause of the malnutrition is multifactorial but, like malnutrition in the acutely
ill patient, it is characterized by disproportionate contraction of lean mass

Stratification of the cancer patient by nutritional status is easily done, and is
constructive since the provision of aggressive nutritional support will improve
outcomes in select groups of malnourished patients

The use of immunoenhancing formulas is indicated in malnourished preoperative
cancer patients since it diminishes perioperative complications