Routine Vitamin Supplementation to Prevent Cancer: Summary of the Evidence, Appendix 2. Excluded Trials

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Appendix 2. Excluded Trials

Study	Population or Nutrients	Reason for Exclusion
Mackerras, 1999¹	Women with CIN; beta-carotene, vitamin C	Wrong outcomes
Manson, 1995²	WACS; Combination	Wrong outcomes
Childers, 1995³	Patients with CIN; Folate	Wrong outcomes
Hercberg, 1999⁴ Hercberg, 1998⁵ SU.VI.MAX Study	Primary prevention; vitamin C, vitamin E, and beta-carotene, 6 mg	Results not available yet
Lonn, 1996⁶ SECURE	Vitamin E	Wrong outcomes
DeMaio, 1992⁷	Post-PTCA vitamin E	Wrong outcomes
Christen, 2000⁸ Physicians Health Study II	Alternate day beta-carotene, alternate day vitamin E, daily vitamin C, and a daily multivitamin in the prevention of total and prostate cancer	Results not available yet
Butterworth, 1992⁹	Patients with cervical dysplasia, folic acid	Wrong outcomes
Hofstad, 1992¹⁰	Patients with polyps: calcium, vitamins A, C, and E, and selenium	Wrong outcomes (polyp growth)
Stephens, 1996¹¹ CHAOS	Vitamin E	Wrong outcomes
Collaborative Group of the Primary Prevention Project¹²	Vitamin E	Wrong outcomes
McLarty, 1992¹³	Vitamin A	Wrong outcomes
Miller, 1997¹⁴	Vitamin E, C, and beta-carotene	Wrong outcomes
Paganelli, 1992¹⁵	Vitamins A, C, and E	Wrong outcomes
Tsubono, 1997¹⁶	Patients with atrophic gastritis	Results not available yet
Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico, 1999¹⁷	Vitamin E	Wrong outcomes
Hoogwerf, 2000¹⁸ Lonn, 1996⁶ Yusuf, 2000¹⁹	Vitamin E	Wrong outcomes
Munoz, 1985²⁰	Vitamin A (esophageal dysplasia)	Wrong outcomes, population
Stich, 1988²¹ Stich, 1988²²	Beta-carotene, vitamin A, and beta-carotene+vitamin A (leucoplakia)	Wrong outcomes
Zaridze, 1993²³	Vitamin A, beta-carotene, and vitamin E (leucoplakia)	Wrong outcomes
Wang, 1994²⁴ Taylor, 1994²⁵ Dawsey, 1994²⁶ Li, 1993²⁷	Retinol and zinc; riboflavin and niacin; vitamin C and molybdenum; and beta-carotene, vitamin E, and selenium	Wrong interventions and possibly wrong outcomes (gastric dysplasia and gastric cancer and esophageal cancer)
Heart Protection Study, 1999²⁸	Vitamin E, vitamin C, and beta-carotene	Wrong outcomes
Wald, 2001²⁹	Folic acid	Wrong outcomes
Skin Cancer Prevention Study, 1990³⁰	Beta-carotene; skin cancer recurrence	Wrong outcomes (nonmelanoma skin cancer only)
Nambour Study^31,32	Beta-carotene; skin cancer (primary prevention)	Wrong outcomes (nonmelanoma skin cancer only)
Southwest Skin Cancer Prevention Study Group³³	Retinol, isotretinoin; skin cancer recurrence	Wrong outcomes (nonmelanoma skin cancer only)
Note: CIN indicates cervical intraephithelial neoplasia; SU.VI.MAX, Supplementation en VItamines et Mineraux Antioxydants; SECURE, Study to Evaluate Carotid Ultrasound changes in patients treated with Ramipril and vitamin E; post-PTCA, post-percutaneous transluminal coronary angioplasty; CHAOS, Cambridge Heart Antioxidant Study.

References

1. Mackerras D, Irwig L, Simpson JM, Weisberg E, Cardona M, Webster F, et al. Randomized double-blind trial of beta-carotene and vitamin C in women with minor cervical abnormalities. Br J Cancer 1999;79:1448-53.

2. Manson JE, Gaziano JM, Spelsberg A, Ridker PM, Cook NR, Buring JE, et al. A secondary prevention trial of antioxidant vitamins and cardiovascular disease in women. Rationale, design, and methods. The WACS Research Group. Ann Epidemiol 1995;5:261-9.

3. Childers JM, Chu J, Voigt LF, Feigl P, Tamimi HK, Ranklin EW, et al. Chemoprevention of cervical cancer with folic acid: a phase III Southwest Oncology Group Intergroup study. Cancer Epidemiol Biomarkers Prev 1995;4:155-9.

4. Hercberg S, Preziosi P, Galan P, Faure H, Arnaud J, Duport N, et al. "The SU.VI.MAX Study": a primary prevention trial using nutritional doses of antioxidant vitamins and minerals in cardiovascular diseases and cancers. SUpplementation on VItamines et Mineraux AntioXydants. Food Chemical Toxicol 1999;37:925-30.

5. Hercberg S, Preziosi P, Briancon S, Galan P, Triol I, Malvy D, et al. A primary prevention trial using nutritional doses of antioxidant vitamins and minerals in cardiovascular diseases and cancers in a general population: the SU.VI.MAX study—design, methods, and participant characteristics. SUpplementation en VItamines et Mineraux AntioXydants. Control Clin Trials 1998;19:336-51.

6. Lonn EM, Yusuf S, Doris CI, Sabine MJ, Dzavik V, Hutchison K, et al. Study design and baseline characteristics of the study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E: SECURE. Am J Cardiol 1996;78:914-9.

7. DeMaio SJ, King SB, di Lembo NJ, Roubin GS, Hearn JA, Bhagavan HN, et al. Vitamin E supplementation, plasma lipids and incidence of restenosis after percutaneous transluminal coronary angioplasty (PTCA). J Am Coll Nutr 1992;11:68-73.

8. Christen WG, Gaziano JM, Hennekens CH. Design of Physicians' Health Study II—a randomized trial of beta-carotene, vitamins E and C, and multivitamins, in prevention of cancer, cardiovascular disease, and eye disease, and review of results of completed trials. Ann Epidemiol 2000;10:125-34.

9. Butterworth CEJ, Hatch KD, Soong SJ, Cole P, Tamura T, Sauberlich HE, et al. Oral folic acid supplementation for cervical dysplasia: a clinical intervention trial. Am J Obstet Gynecol 1992;166:803-9.

10. Hofstad B, Vatn M, Hoff G, Larsen S, Osnes M. Growth of colorectal polyps: design of a prospective, randomized, placebo-controlled intervention study in patients with colorectal polyps [published erratum appears in Eur J Cancer Prev 1993 Mar;2(2):189]. Eur J Cancer Prev 1992;1:415-22.

11. Stephens NG, Parsons A, Schofield PM, Kelly F, Cheeseman K, Mitchinson MJ. Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet 1996;347:781-6.

12. Collaborative Group of the Primary Prevention Project. Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice. Collaborative Group of the Primary Prevention Project. Lancet 2001;357:89-95.

13. McLarty JW. An intervention trial in high-risk asbestos-exposed persons. Adv Exp Med Biology 1992;320:141-9.

14. Miller ER, Appel LJ, Levander OA, Levine DM. The effect of antioxidant vitamin supplementation on traditional cardiovascular risk factors. J Cardiovasc Risk 1997;4:19-24.

15. Paganelli GM, Biasco G, Brandi G, Santucci R, Gizzi G, Villani V, et al. Effect of vitamin A, C, and E supplementation on rectal cell proliferation in patients with colorectal adenomas. J Natl Cancer Inst 1992;84:47-51.

16. Tsubono Y, Okubo S, Hayashi M, Kakizoe T, Tsugane S. A randomized controlled trial for chemoprevention of gastric cancer in high-risk Japanese population; study design, feasibility and protocol modification. Jpn J Cancer Res 1997;88:344-9.

17. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Lancet 1999;354:447-55.

18. Hoogwerf BJ, Young JB. The HOPE study. Ramipril lowered cardiovascular risk, but vitamin E did not. Cleve Clin J Med 2000;67:287-93.

19. Yusuf S, Dagenais G, Pogue J, Bosch J, Sleight P. Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000;342:154-60.

20. Munoz N, Wahrendorf J, Bang LJ, Crespi M, Thurnham DI, Day NE, et al. No effect of riboflavine, retinol, and zinc on prevalence of precancerous lesions of oesophagus. Randomised double-blind intervention study in high-risk population of China. Lancet 1985;2:111-4.

21. Stich HF, Hornby AP, Mathew B, Sankaranarayanan R, Nair MK. Response of oral leukoplakias to the administration of vitamin A. Cancer Lett 1988;40:93-101.

22. Stich HF, Rosin MP, Hornby AP, Mathew B, Sankaranarayanan R, Nair MK. Remission of oral leukoplakias and micronuclei in tobacco/betel quid chewers treated with beta-carotene and with beta-carotene plus vitamin A. Int J Cancer 1988;42:195-9.

23. Zaridze D, Evstifeeva T, Boyle P. Chemoprevention of oral leukoplakia and chronic esophagitis in an area of high incidence of oral and esophageal cancer. Ann Epidemiol 1993;3:225-34.

24. Wang GQ, Dawsey SM, Li JY, Taylor PR, Li B, Blot WJ, et al. Effects of vitamin/mineral supplementation on the prevalence of histological dysplasia and early cancer of the esophagus and stomach: results from the General Population Trial in Linxian, China. Cancer Epidemiol Biomarkers Prev 1994;3:161-6.

25. Taylor PR, Li B, Dawsey SM, Li JY, Yang CS, Guo W, et al. Prevention of esophageal cancer: the nutrition intervention trials in Linxian, China. Linxian Nutrition Intervention Trials Study Group. Cancer Res 1994;54:2029s-2031s.

26. Dawsey SM, Wang GQ, Taylor PR, Li JY, Blot WJ, Li B, et al. Effects of vitamin/mineral supplementation on the prevalence of histological dysplasia and early cancer of the esophagus and stomach: results from the Dysplasia Trial in Linxian, China. Cancer Epidemiol Biomarkers Prev 1994;3:167-72.

27. Li JY, Li B, Blot WJ, Taylor PR. [Preliminary report on the results of nutrition prevention trials of cancer and other common diseases among residents in Linxian, China] [Chinese]. Chung-Hua Chung Liu Tsa Chih [Chinese Journal of Oncology] 1993;15:165-81.

28. MRC/BHF Heart Protection Study of cholesterol-lowering therapy and of antioxidant vitamin supplementation in a wide range of patients at increased risk of coronary heart disease death: early safety and efficacy experience. Eur Heart J 1999;20:725-41.

29. Wald DS, Bishop L, Wald NJ, Law M, Hennessy E, Weir D, et al. Randomized trial of folic acid supplementation and serum homocysteine levels. Arch Intern Med 2001;161:695-700.

30. Greenberg ER, Baron JA, Stukel TA, Stevens MM, Mandel JS, Spencer SK, et al. A clinical trial of beta carotene to prevent basal-cell and squamous-cell cancers of the skin. The Skin Cancer Prevention Study Group [published erratum appears in N Engl J Med 1991 Oct 31;325(18):1324]. N Engl J Med 1990;323:789-95.

31. Green A, Williams G, Neale R, Hart V, Leslie D, Parsons P, et al. Daily sunscreen application and betacarotene supplementation in prevention of basal-cell and squamous-cell carcinomas of the skin: a randomised controlled trial. Lancet 1999;354:723-9.

32. Ambler JS, Hirst LW, Clarke CV, Green AC. The Nambour study of ocular disease. I. Design, study population and methodology. Ophthalmic Epidemiol 1995;2:137-44.

33. Levine N, Moon TE, Cartmel B, Bangert JL, Rodney S, Dong Q, et al. Trial of retinol and isotretinoin in skin cancer prevention: a randomized, double-blind, controlled trial. Southwest Skin Cancer Prevention Study Group. Cancer Epidemiol Biomarkers Prev 1997;6:957-61.

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