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Chris Parker

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Title: Chris Parker


1
Nutritional Intervention for Prostate Cancer
  • Chris Parker

2
Randomised controlled trials of nutritional
intervention and prostate cancer Past, present
and future
  • Chris Parker
  • CR-UK Clinician Scientist Fellow
  • Institute of Cancer Research
  • and Royal Marsden Hospital

Dr Parker has received consultant fees from
Sanofi-Aventis
3
(No Transcript)
4
Can nutrition explain the pattern of
international epidemiology of hormone-dependent
cancers?
  • The most plausible hypothesis..is that some
    components of the Western high-protein, high-fat
    diet acting in early life make individuals prone
    to develop these cancers.

Berg JW. Cancer Res. 1975
5
(No Transcript)
6
Nutritional intervention and prostate cancer
recommendations
  • More
  • Selenium
  • Soya
  • Sunlight
  • Oily fish
  • Tomato products
  • Onions
  • Green tea
  • Red wine
  • Vitamin E
  • Zinc
  • Less
  • Red meat
  • Dairy products
  • Saturated fat
  • Obesity
  • Calcium
  • Zinc

7
Nutritional intervention and prostate cancer my
recommendations
  • More
  • RESEARCH
  • Less
  • DOGMA

8
Randomised controlled trials of nutritional
intervention and prostate cancer Past, present
and future
  • Past
  • Nutritional Prevention of Cancer trial
  • Alpha-tocopherol beta-carotene trial
  • SUVIMAX trial
  • Physicians Health Study
  • CARET

9
The Nutritional Prevention of Cancer TrialClark
et al. JAMA (1996)Duffield-Lillico et al. BJU
Int (2003)
  • Patients and methods
  • 1983-1991
  • 200 µg/day selenium vs placebo
  • 1312 patients with non-melanoma skin cancer from
    Eastern USA
  • 980/1312 male
  • 927 had baseline bloods and no history of PCa

10
The Nutritional Prevention of Cancer TrialClark
et al. JAMA (1996)Duffield-Lillico et al. BJU
Int (2003)
  • Results
  • Mean follow-up 7.5 years
  • 64 cases of PCa
  • 22 selenium, 42 placebo
  • HR 0.48 (0.28-0.80 p0.005)
  • Analysis by baseline plasma selenium levels
  • Lowest tertile HR 0.14 (0.03-0.61)
  • Middle tertile HR 0.33 (0.13-0.82)
  • Highest tertile HR 1.14 (0.51-2.59)

11
The Nutritional Prevention of Cancer TrialClark
et al. JAMA (1996)Duffield-Lillico et al. BJU
Int (2003)
  • Limitations
  • PCa not primary endpoint
  • Only 64 cases
  • Unexplained, significant difference in prostate
    biopsy rates between trial arms

12
Finnish Alpha-Tocopherol, Beta-Carotene (ATBC)
Cancer Prevention Study (1985-93)JNCI (1998)
90440, JAMA (2003) 290476
  • Patients and methods
  • 1985-93, Finland
  • 29,133 male smokers, aged 50-69 years
  • Placebo-controlled, randomised, factorial trial
    of a-tocopherol (50 mg/day) and ß-carotene (20mg)

13
Finnish Alpha-Tocopherol, Beta-Carotene (ATBC)
Cancer Prevention Study (1985-93)JNCI (1998)
90440, JAMA (2003) 290476
14
Anti-oxidant and vitamin supplementation in the
SUVIMAX trial Meyer et al. Int J Cancer (2005)
  • 5141 healthy men, aged 45-60
  • Placebo controlled trial of supplement (120mg
    vitamin C, 30mg a-tocopherol, 6mg ß-carotene,
    100µg selenium, 20 mg zinc)
  • Median follow-up 9 years
  • 103 cases of PCa
  • Overall HR 0.88 (0.60-1.29)

15
Effects of beta-carotene supplementation on
cancer incidence in the Physicians' Health
StudyCook et al. Cancer Causes Control (2000)
  • a randomized trial of beta-carotene (50 mg,
    alternate days)
  • 22,071 US male physicians
  • 1117 prostate Ca cases
  • (RR 1.0, 95 CI 0.9-1.1)

16
The beta-carotene and retinol trial (CARET)Omenn
et al. JNCI (1996)
  • 12,025 males at risk of lung Ca
  • ß-carotene (30mg) and 25,000 IU retinol versus
    placebo
  • Stopped early with excess lung Ca and overall
    mortality
  • 300 P Ca cases
  • RR 1.01 (0.80-1.27)

17
Randomised controlled trials of nutritional
intervention and prostate cancer Past, present
and future
  • Past
  • Nutritional Prevention of Cancer trial
  • Alpha-tocopherol beta-carotene trial
  • SUVIMAX trial
  • Physicians Health Study
  • CARET

18
Effects of Long-term Vitamin E Supplementation on
Cardiovascular Events and Cancer A Randomized
Controlled Trial The HOPE Trial Investigators.
JAMA 20052931338-1347
.
19
A Randomized Trial of Antioxidant Vitamins to
Prevent Second Primary Cancers in Head and Neck
Cancer Patients Bairati et al. J Natl Cancer
Inst 200597481-488
Freedom from second primary cancers
  • patients receiving Vitamin E supplements had a
    higher rate of second primary cancers during the
    supplementation period (HR 2.88, 95 CI 1.56
    to 5.31)

20
Randomised controlled trials of nutritional
intervention and prostate cancer Past, present
and future
  • Present
  • SELECT
  • Physicians Health Study II
  • 14,000 men
  • Vitamin C, vitamin E, multivitamins
  • SWOG phase III trials of selenium
  • HG PIN
  • Negative biopsies
  • 3 randomised phase II trials (genistein, vitamin
    D, selenium) in pre-op setting

21
  • SELECT
  • 32,400 men
  • 12 year follow-up

22
Randomised controlled trials of nutritional
intervention and prostate cancer Past, present
and future
  • Present
  • SELECT
  • Physicians Health Study II
  • 14,000 men
  • Vitamin C, vitamin E, multivitamins
  • SWOG 9917
  • phase III trial of selenium
  • HG PIN
  • 3 randomised phase II trials (genistein, vitamin
    D, selenium) in pre-op setting

23
Randomised controlled trials of nutritional
intervention and prostate cancer Past, present
and future
  • Future

24
Randomised controlled trials of nutritional
intervention and prostate cancer Past, present
and future
  • Future
  • Need efficient trial design to test multiple
    interventions in modest numbers of patients in
    short period of time

25
Types of prevention study
Gescher et al. Lancet Oncology 20012(1)371
26
Proposal for randomised, multi-arm phase II/III
tertiary prevention of prostate cancer trial
Main phase primary endpoint clinical DFS
27
Intensive lifestyle changes may affect the
progression of prostate cancerOrnish et al. J
Urol (2005) 174 1065-70
  • Patients and methods
  • T1/2, GS lt7, PSA lt 10 prostate cancer on watchful
    waiting
  • Randomly allocated to intensive lifestyle
    program
  • Vegan diet
  • soy supplement
  • Fish oil 3g daily
  • Vitamin E 400 IU daily
  • Selenium 200 µg daily
  • Vitamin C 2g daily
  • Walking 30 mins 6 days/week
  • Stress management techniques 60 minutes daily
  • 1 hour support group weekly

28
Intensive lifestyle changes may affect the
progression of prostate cancerOrnish et al. J
Urol (2005) 174 1065-70
  • Results
  • 93 cases
  • 95 adherence over 1 year!
  • 6/44 withdrew from intervention within 12 months
    to have radical treatment (vs 0/49)
  • Mean PSA change -0.25 vs 0.38ng/ml, p 0.016
  • Serum inhibition of LNCaP growth 70 vs 9,
    plt0.001

29
Randomised controlled trials of nutritional
intervention and prostate cancer Past, present
and future
  • evidence to support a possible preventative role
    for a wide range of nutritional interventions
  • traditional primary prevention studies are too
    slow and expensive
  • Tertiary prevention setting provides an
    opportunity to accelerate progress

30
Prostate cancer Rx of the future
Cure or control?
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