Chris Parker

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Nutritional Intervention for Prostate Cancer

• Chris Parker

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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
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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
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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

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Nutritional intervention and prostate cancer my
recommendations

• More
• RESEARCH

• Less
• DOGMA

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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

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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

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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)

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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

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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)

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Finnish Alpha-Tocopherol, Beta-Carotene (ATBC)
Cancer Prevention Study (1985-93)JNCI (1998)
90440, JAMA (2003) 290476
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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)

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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)

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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)

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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

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Effects of Long-term Vitamin E Supplementation on
Cardiovascular Events and Cancer A Randomized
Controlled Trial The HOPE Trial Investigators.
JAMA 20052931338-1347
.
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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)

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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

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

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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

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

• Future

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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

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Types of prevention study
Gescher et al. Lancet Oncology 20012(1)371
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Proposal for randomised, multi-arm phase II/III
tertiary prevention of prostate cancer trial
Main phase primary endpoint clinical DFS
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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

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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

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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

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Prostate cancer Rx of the future
Cure or control?