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Chemoprevention of Ovarian Cancer: Is There a Role for Diet and Physical Activity Interventions? David S. Alberts, M.D.

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Presentation on theme: "Chemoprevention of Ovarian Cancer: Is There a Role for Diet and Physical Activity Interventions? David S. Alberts, M.D."— Presentation transcript:

1 Chemoprevention of Ovarian Cancer: Is There a Role for Diet and Physical Activity Interventions? David S. Alberts, M.D.

2 Background The five year relative survival rate for ovarian cancer between 1996 and 2002 was 45%*The five year relative survival rate for ovarian cancer between 1996 and 2002 was 45%* –For regional and distant disease, 5 year survival rates are 69% and 305, respectively* More than 70% of women who experience a clinical CR on primary chemotherapy experience disease recurrence and ultimately die**More than 70% of women who experience a clinical CR on primary chemotherapy experience disease recurrence and ultimately die** Efforts to identify lifestyle modifications that may modulate disease incidence and progression remain limitedEfforts to identify lifestyle modifications that may modulate disease incidence and progression remain limited The role of diet and specific dietary constituents in ovarian cancer survival is not clearly understoodThe role of diet and specific dietary constituents in ovarian cancer survival is not clearly understood –Diet and exercise remain potential modifiable risk factors for this disease * American Cancer Society, Cancer Facts and Figures 2007, Atlanta: American Cancer Society; 2007 **Bosetti C et al. Curr. Opin. Obstet. Gynecol., 14:13, 2002 * American Cancer Society, Cancer Facts and Figures 2007, Atlanta: American Cancer Society; 2007 **Bosetti C et al. Curr. Opin. Obstet. Gynecol., 14:13, 2002

3 Background-Diet Supports low fat diets in the primary prevention of ovarian cancer (WHI n=48,835 post-menopausal women)Supports low fat diets in the primary prevention of ovarian cancer (WHI n=48,835 post-menopausal women) Prentice R, Thomson CA, et al. JNCI, 99:1534, 2007 * Hazard ratio was 0.60 (955 CI = 0.38 to 0.96, p=0.03 for the follow-up over the last 4 years ( years)

4 YEARS PATIENTS (%) Diet Control HR, 95% CI P-value* 96/ / , Diet Control * From adjusted Cox proportional hazards model including: stratification factors, ER status, tumor size, and surgery (mastectomy/lumpectomy), p value = by unadjusted log rank test Absolute difference 1% 3% 4%7% Chlebowski RT et al., J. Natl. Cancer Inst., 98:1767, 2006

5 P-value from adjusted Cox proportional hazard model Diet Control Control Diet _____ Diet Control HR, 95% CI P-value 28/205 59/ , Absolute difference:6% 8%11% 6% YEARS PATIENTS (%) Chlebowski RT et al., J. Natl. Cancer Inst., 98:1767, 2006

6 Pierce JP et al., J. Clin. Oncol., 25:2345, 2007 Womens Health Eating and Living Study re-analysis women who followed both diet and exercise recommendations had lower recurrence and better survival rates

7 Background-Diet Population based ovarian cancer case-control across 3 Australian states( )Population based ovarian cancer case-control across 3 Australian states( ) 609 women with invasive epithelial ovarian cancer609 women with invasive epithelial ovarian cancer Diet assessed with food frequency questionnaireDiet assessed with food frequency questionnaire Deaths identified though state cancer registries and national death indexDeaths identified though state cancer registries and national death index Nagle, Christina M et al. Int J Cancer, 106:264, 2003

8 Dietary Influences on Survival After Ovarian Cancer Christina M. Nagle 1, David M. Purdie 1,2, Penelope M. Webb 1,2, Adele Green 1,2, Philip W. Harvey 1 and Christopher J. Bain 1 1 School of Population Health, University of Queensland, Brisbane, Australia 2 Queensland Institute of Medical Research, Brisbane, Australia

9 Nagle CM et al., Int J Cancer, 106:264, 2003 Dietary Influences on Survival after Ovarian Cancer

10 Increased intake of lactose and galactose have specifically been identified to increase ovarian cancer risk in select populations by both Cozen et al. and Nagle et al. Cozen W et al., Cancer Causes Control., 13:113, 2002 & Nagle CM et al., Int J Cancer, 106:264, 2003 Possible a Priori Harmful Prognostic Factors for Ovarian Cancer

11 Effects of Food Groups on Survival from Epithelial Ovarian Cancer Long-term Follow up of a Cook County Case Control Study* Food Median Hazard GroupServings/Week N Ratio p-value Vegetables 0< <0.05 7< < <0.05 Cruciferous Vegetables 0< <0.05 1< < Red Meats 0< <0.05 1< < <0.01 Milk (all types) <0.05 >0< < <0.01 *Dolecek, TA, Davis FG, Campbell RT, Joslin CE. Diet and survival from ovarian cancer among women in Cook County, IL. Am. J. Epidemiol

12 Kushi LH et al., Am J Epidemiol, 149:21, 1999 Relative risks and 95% confidence intervals of ovarian cancer among 29,083 postmenopausal women, Iowa Womens Health Study,

13 Summary-Diet Select dietary constituents have been suggested to reduce ovarian cancer risk.Select dietary constituents have been suggested to reduce ovarian cancer risk. –Green leafy vegetables (RR= , p for trend, 0.01) Iowa Womens Health Study* –Cholesterol intake (RR= ; p for trend, 0.06) Iowa Womens Health Study* Consumption of greater than four eggs/week (RR= , p for trend, 0.04)*Consumption of greater than four eggs/week (RR= , p for trend, 0.04)* Increased risk associated with egg intake was corroborated in Australian women**Increased risk associated with egg intake was corroborated in Australian women** *Kushi LH et al., Am. J. Epidemiol., 149:21, 1999 **Pirozzo S et al., Cancer Epidemiol Biomarkers Prev, 11:1112, 2002

14 Summary-Diet –Protective effects for high vegetable intake (RR= 0.61 for three servings per day versus less than one, (CI: ) * Case (n=605) control (N=3899) study of newly diagnosed epithelial ovarian cancerCase (n=605) control (N=3899) study of newly diagnosed epithelial ovarian cancer –These findings are supported in the widely recognized WCRF/AICR report that also evaluated diet and ovarian cancer** *Riman T et al., Eur. J. Epidemiol., 19:1011, 2004 **Glade MJ et al., Nutrition, 15:523, 1999

15 Background-Physical Activity Mechanisms by which physical activity may exert protective effectMechanisms by which physical activity may exert protective effect –Improving immune functioning –Reduction of ovarian estrogen production (via delay of menarche and reduction of cycling in young women) –Reducing body fat (thereby reducing fat-produced estrogens along with potential for storage and turnover of fat-soluble carcinogens) –Increasing sex-hormone binding globulins –reducing circulating insulin and glucose –Reducing activity of COX-2 and levels of prostaglandins in ovarian epithelium

16 Relative Risks and 95% Confidence Intervals for Ovarian Cancer in Relation to Leisure-Time Physical Activity: Iowa Womens Health Study, Increased risk of ovarian cancer development among women with the highest levels of physical activity Anderson JP et al., Cancer, 100:1515, 2004

17 Relative Risks and 95% Confidence Intervals for Ovarian Cancer in Relation to Baseline Anthropometric Variable: Iowa Womens Health Study, Increased risk of ovarian cancer development among women with higher waist-to-hip ratios Anderson JP et al., Cancer, 100:1515, 2004

18 Significantly reduced risk of ovarian cancer among women in the highest tertiles of moderate, recreational activity Odds Ratios for Ovarian Cancer Associated With Moderate and Vigorous Recreational Physical Activity, Overall and by Menopausal Status, NECSS Study, Canada, Pan SY et al., Int. J. Cancer, 117:300, 2005

19 The Netherlands Cohort Study Reported an Inverse Association Between Moderate Physical Activity and Ovarian Cancer Risk Same study looked at using participation in sport (competition) as a marker for vigorous activity finding no association of vigorous activity with ovarian cancer risk.Same study looked at using participation in sport (competition) as a marker for vigorous activity finding no association of vigorous activity with ovarian cancer risk. Women who reported sport participation (i.e. vigorous physical activity) tended to differ from the overall population: taller, lower BMI, greater daily alcohol intake, and fewer childrenWomen who reported sport participation (i.e. vigorous physical activity) tended to differ from the overall population: taller, lower BMI, greater daily alcohol intake, and fewer children Biesma RG et al., Cancer Causes Control, 17:109, 2006

20 GOG-225 Can Diet and Physical Activity Modulate Ovarian Cancer Progression Free Survival?

21 Study Chair David S. Alberts, M.D. Study Co-Chairs Cynthia Thomson, Ph.D., R.D., C.O.N.S. Janet Foote, Ph.D. Robert Mannel, M.D. Quality of Life Co-Chair Karen Basen-Engquist, Ph.D, MPH Statististician Marion Piedmont, M.S. Translational Scientisist Zoe Miner, Ph.D. Biomarkers Studies

22 Schema-GOG-225 Ovarian Cancer Diagnosis: Successful first line treatment consolidation Comparison Lifestyle Intervention Lifestyle: 6 servings of fruits and vegetables (incl. 1 cruciferous), low fat, (weight control ) additional steps daily 2:1 intervention: comparison Progression- free survival 2 years) RANDOMIZERANDOMIZE

23 Primary Objective Determine if disease-free women who completed therapy for Stage III-IV ovarian or primary peritoneal cancer randomized to a healthy lifestyle intervention have increased progression free survival compared to those randomized to usual care.Determine if disease-free women who completed therapy for Stage III-IV ovarian or primary peritoneal cancer randomized to a healthy lifestyle intervention have increased progression free survival compared to those randomized to usual care.

24 Secondary Objective Determine if women in the intervention group have improved general quality of lifeDetermine if women in the intervention group have improved general quality of life –Measured by General Health subscale of RAND-36 Determine if women in the intervention group have improved physical functioningDetermine if women in the intervention group have improved physical functioning –Measured by the Physical Functioning subscale of RAND-36 and the GSRS-IBS

25 Eligibility Criteria Diagnosis of epithelial ovarian or primary peritoneal carcinomaDiagnosis of epithelial ovarian or primary peritoneal carcinoma –Stage III or IV at diagnosis Completion of all primary chemotherapy and consolidation therapy > 12 weeks prior to enrollment and 12 weeks prior to enrollment and < 24 months from enrollment Complete remissionComplete remission –No clinical evidence of persistent or recurrent disease based on CA-125 and CT scan. GOG Performance Grade of 0, 1, or 2.GOG Performance Grade of 0, 1, or 2.


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