Transcript Dietary Therapy of Prostate Cancer - PC-REF

Diet and Stress Reduction
in Advanced Prostate Cancer
GORDON A. SAXE, MD, PhD
UNIVERSITY OF CALIFORNIA, SAN DIEGO
Rebecca and John Moores UCSD Cancer Center
Dept. of Family and Preventive Medicine
Primary Research Question:
 Can healthy dietary change, reinforced by
stress reduction, slow or stop the progression of
advanced prostate cancer?
Rationale
 Prostate cancer is the most commonly
occurring cancer (other than skin cancer)
among men in the U.S.
 In 1995, there were 244,000 new cases and
44,000 deaths from prostate cancer in the U.S.
Rationale
 One in six men in the U.S. will develop
invasive prostate cancer in his lifetime.
 One in four African-American men will
develop invasive prostate cancer.
Rationale
 Following initial treatment, one in three
patients will have a biochemical recurrence
(marked by a rising PSA) within 10 years.
 Biochemical recurrence implies that there is
microscopic evidence of cancer that has spread
beyond the prostate.
Rationale
 One third of those with a biochemical
recurrence will develop clinical evidence of
metastatic disease within the subsequent five
years.
 No curative therapy exists for metastatic
prostate cancer.
Rationale
 Hormonal therapy can induce partial or
complete remission and palliate symptoms.
 However, its effects are only temporary, lasting
an average of 18 – 24 months.
Rationale
 Hormone therapy is also accompanied by
unpleasant side-effects such as hot flashes,
fatigue, impotence, gynecomastia,
osteoporosis, and muscle loss.
 As a result, patients with rising PSA after
surgery tend to feel anxious and helpless in the
face of their illness, a condition referred to as
“PSA anxiety.”
Rationale
 Risk factors for prostate cancer:
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Male gender
Age
Heredity (genetic polymorphisms)
Vasectomy
Race
Diet
International Variation
China
Sweden
United States
1.3 per 100,000
55.3 per 100,000
102.1 per 100,000
Rationale
 Epidemiological and laboratory evidence has
associated specific dietary intakes with prostate
cancer incidence, mortality, and possibly even
disease progression:
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Meat
Dairy food
Saturated fat
Rationale
 Other dietary factors appear to be protective:
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Whole grains
Vegetables, especially cabbage family
Tomatoes and other lycopene-rich foods
Vitamin E, Selenium, and Zinc
Green tea
Soy foods (?)
Rationale
 However, it is critical to promote stress reduction
along with dietary change:
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A major change in eating habits can be quite
stressful.
Many of these patients are already suffering
from “PSA anxiety.”
Stress reduction (such as meditation and yoga)
may help patients to focus and make better
dietary selections.
Primary Research Question
 Can healthy dietary change, reinforced by stress
reduction, slow or stop the progression of
advanced prostate cancer?
Definitions
 Healthy dietary change: increased whole grains
and vegetables, decreased saturated fat
 Stress reduction: meditation, yoga, social
support, mild exercise
 Advanced prostate cancer: rising PSA on serial
PSA tests after post-surgical PSA nadir
Findings from our Pilot Study
“Can Diet in Conjunction with Stress Reduction
Affect the Rate of Increase in Prostate Specific
Antigen after Biochemical Recurrence of
Prostate Cancer?”
Saxe GA, Hebert JR, Kabat-Zinn J, et al
Journal of Urology, 166(12): 2202-7, Dec., 2001
Methods
 Small non-randomized pilot study
 Subjects (N=10) were men who had undergone
radical prostatectomy and had subsequent rising
PSA on serial tests
 Pre/post study design with each subject serving
as his own control
Methods
 Pre- vs. post-intervention rates of PSA increase
and doubling times were compared.
 Data also gathered on diet, physical activity, and
body weight
Intervention
 Group-based intervention consisting of a series
of 12 weekly classes, with each class lasting 3-4
hours
 Subjects were asked to be accompanied by a
support person, preferably someone with whom
they shared meals.
Intervention
 Each class included a cooking demonstration,
hands-on training in prostate-healthy meal
preparation, and a didactic presentation on diet
and health.
 Classes also included formal instruction and
practice in meditation and yoga (with subjects
asked to practice daily at home).
Results
 Signed rank test found significant reduction in
the rate of PSA increase for the group as a whole
(p=.01).
Results
Pre
Post
Mean Slope
0.124
0.031
95% C.I.
[0.076 - 0.173]
[0.012 - 0.075]
Median
Doubling Time
6.5 months
17.7 months
95% C.I.
[3.7 - 10.1]
[7.8 - 
Results
 Eight out of ten subjects showed a decrease in
their rates of PSA increase.
Figure 1. Change in PSA slopes
(pre-study – post-study) by subject
Change in PSA Slope
.1
Log
PSA
0
-.1
-.2
1
2
3
4
5
6
-.3
Subject #
7
8
9
10
Results
 Three subjects had absolute reductions in their
PSA levels.
Figure 2. PSA slopes, paired (pre-study
vs. post-study), by subject
Pre-study
Slope
Post-study
Slope
.3
Log
.2
PSA
.1
0
-.1
1
2
3
4
5
6
Subject #
7
8
9
10
Figure 3. Change in fiber intake as a
predictor of change in PSA slope
0.10
Change in
PSA Slope
0.00
-0.10
(log PSA)
-0.20
-0.30
-20.00
0.00
20.00
Change in Fiber Intake (g/day)
Spearman  = -.73, p=.02
40.00
Figure 4. Change in exercise level as a
predictor of change in PSA slope
0.10
0.00
Change in
PSA Slope
(log PSA)
-0.10
-0.20
-0.30
0.00
70.00
140.00
Change in Exercise Level (mins./ day)
Spearman’s  = -.60, p=.04
Figure 5. Change in body mass index as
a predictor of change in PSA slope
0.10
0.00
Change in
PSA Slope
(log PSA)
-0.10
-0.20
-0.30
-4.00
-3.00
-2.00
-1.00
0.00
Change in Body Mass Index (kg/m2)
Spearman’s  = .60, p=.04
Conclusions
 In this small sample we saw a significant
reduction in the rate of increase in PSA in men
with biochemically recurrent prostate cancer.
 Major changes in diet and lifestyle were feasible
in a relatively short period of time.
Conclusions
 An intervention of this type may provide a
means for men with recurrent prostate cancer to
slow the progression of their disease without
adverse side effects while simultaneously
improving their well being and quality of life.
 These PSA results are promising and warrant
further investigation through a larger multi-arm,
randomized trial.
Current Research
“Diet and Stress Reduction in Recurrent
Prostate Cancer”
Gordon A. Saxe, MD, PhD
Cheryl L. Rock, PhD, RD
Dan Mercola, MD, PhD
Carol Salem, MD
Differences with Pilot Study

Randomized trial (pilot was pre-post design)

Larger sample size (N=50)

Longer intervention period (6 months vs. 4)

More funding!!
Study Design

Subjects randomized to intervention or control
status

Intervention subjects receive program similar to
subjects in pilot study

Control subjects asked to maintain usual diet for 6
months and undergo same monitoring as those in
intervention
Eligibility Criteria

Biopsy-confirmed prostate cancer

Primary therapy consisting of surgery or radiation
treatment

Rising PSA, documented on a minimum of three
serial tests within a 12-month period, after
achieving post-treatment nadir
Eligibility Criteria

No use of hormone therapy within the last 12
months

No competing health conditions that would limit
participation

Age 18 or older
Monitoring

Occurs at baseline, 3 months, and 6 months postbaseline

Body weight assessment
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Blood draws for PSA, plasma carotenoids, and
other biomarkers of tumor metastasis
Questionnaires

Identifying and demographic data

Food frequency questionnaire

Physical activity recall
Questionnaires

Spielberg Anxiety Scale

Diet-related quality of life
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FACT-P
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SF-36
Data Analysis

Primary analysis will test the hypothesis
that subjects in the intervention group will
have a lower rate of increase in PSA than
control subjects over the course of the 6month intervention period

We will also test differences in mean PSA
rates and doubling times between
intervention and control subjects
Data Analysis:

We will also examine:
– The effect of the intervention on quality of
life
– Changes in other biomarkers of tumor
metastasis
– Degree of dietary and lifestyle change by
men in the intervention.
Eligibility Criteria

Biopsy-confirmed prostate cancer

Primary therapy consisting of surgery or radiation
treatment

Rising PSA, documented on a minimum of three
serial tests within a 12-month period, after
achieving post-treatment nadir
Eligibility Criteria

No use of of hormone therapy within the last 12
months

No competing health conditions that would limit
participation

Age 18 or greater
Contact Information:
GORDON A. SAXE, MD, PhD
UNIVERSITY OF CALIFORNIA, SAN DIEGO
Rebecca and John Moores UCSD Cancer Center
Dept. of Family and Preventive Medicine
Tel. (858) 622-1731, ext. 2233
Email: [email protected]
Sample Size Considerations

N = 50 subjects (25 intervention, 25 control)

Based on following assumptions:
– Two-sided t-test
– Mean PSA doubling time will increase by 100%
(from 245 days to 490 days) (pilot = 937 days)
– Standard deviation = 227 days (same as pilot)
– Alpha = .05
– Study power = 80%
– Dropout rate < 40%
Data Analysis

PSA doubling time is defined as:
PSA-DT = (ln2 [0.639]/slope)