NPCT 2002
| Methods | Randomised controlled trial Nutritional Prevention of Cancer Trial (NPCT) Allocation: random, block/stratified by clinic Sequence generation: computer generated random numbers Concealment: central assignment (sealed pill bottles) Blinding: participant blinded, doctor blinded, outcome assessor/pathologist unclear, review/coding of medical records blinded Dropouts/withdrawals: “9 patients (5 in the selenium group and 4 in the placebo group) declined to provide additional illness information” (Clark 1996, p. 1959) ‐ 0 participants lost to vital follow‐up Intention‐to‐treat‐analysis: yes Recruitment period: 1983 to 1991 End of predefined study period: 31 December 1993 Blinded intervention continued until the end of the blinded period: 31 January 1996 Intervention duration: 31 December 1993 (end of study period): mean = 4.5 years 31 January 1996 (end of blinded period): mean = 7.9 years Observation period/dermatologic follow‐up: 31 December 1993 (end of study period): mean = 6.4 years 31 January 1996 (end of blinded period): mean = 7.4 years Detection of cases: dermatologic examination and interview every 6 months during follow‐up; incident BCC and SCC were diagnosed by biopsy and confirmed by another dermatopathologist Informed consent: written informed consent forms, approval by institutional review board of participating institutions |
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| Participants |
Country: US Number of participants: 1312 (randomised to selenium group: 653, to placebo group: 659) Condition: male and female participants with history of 2 or more squamous cell or basal cell skin cancers Demographics: mean age 63.4 years (selenium)/63.0 years (placebo); 73.8% men (selenium). 75.6% men (placebo) Recruitment and setting: seven dermatological clinics (three academic units, four private practices) in the US |
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| Interventions |
Intervention: 200 µg selenium supplied as 500 mg selenium yeast tablets p.o./daily. Control: placebo |
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| Outcomes |
Primary outcome measure: incidence of basal and squamous cell carcinoma of the skin: all analyses were based on 1250 participants with initial blood collection within four days after randomisation (621 in the selenium group and 629 in the placebo group) Other reported outcomes and secondary outcome measures: Reported in Clark 1996: Incidence of lung cancer, prostate cancer, colorectal cancer, any cancer, head and neck cancer, bladder cancer, oesophageal cancer, breast cancer, melanoma, haematologic cancer, Reported in Duffield‐Lillico 2002: Overall cancer mortality |
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| Risk estimates [95% CI] |
Primary outcomes: 1) at the end of study period (31 December 1993) (Clark 1996): BCC: RR 1.10 (95% CI 0.95 to 1.28); cases: selenium group: 377, placebo group: 350; incidence per person‐year under follow‐up: selenium group 0.16, placebo group 0.15 SCC: RR 1.14 (95% CI 0.93 to 1.39); cases: selenium group 218, placebo group: 190; incidence per person‐year under follow‐up: selenium group 0.07, placebo group 0.06 2) at the end of blinded period (31 January 1996) (Duffield‐Lillico 2003): BCC: RR 1.17 (95% CI 1.02 to 1.35), HR 1.09 (95% CI 0.94 to 1.26); number of cases not reported; incidence per person‐year under follow‐up: selenium group: 0.16, placebo group 0.13 SCC: RR 1.32 (95% CI 1.09 to 1.60), HR 1.25 (95% CI 1.03 to 1.51); number of cases not reported; incidence per person‐year under follow‐up: selenium group: 0.05, placebo group 0.07 NMSC: RR 1.27 (95% CI 1.11 to 1.45) HR 1.17 (95% CI 1.02 to 1.34); number of cases not reported; incidence per person‐year under follow‐up: selenium group: 0.20, placebo group 0.16 Other reported outcomes and secondary outcomes: 1) at the end of study period (31 December 1993) (Clark 1996): lung cancer RR 0.54 (95% CI 0.30 to 0.98), adjusted HR 0.56 (95% CI 0.31 to 1.01) cases selenium: 17, placebo: 31 prostate cancer RR 0.37 (95% CI 0.18 to 0.71), adjusted HR 0.35 (95% CI 0.18 to 0.65) cases selenium: 13, placebo: 35 colorectal cancer RR 0.42 (95% CI 0.18 to 0.95), adjusted HR 0.39 (95% CI 0.17 to 0.90) cases selenium: 8, placebo: 19 any cancer RR 0.63 (95% CI 0.47 to 0.85), adjusted HR 0.61 (95% CI 0.46 to 0.82) cases selenium: 77, placebo: 119 head and neck cancer RR 0.74 (95% CI 0.21 to 2.43), adjusted HR 0.77 (95% CI 0.27 to 2.24) cases selenium: 6, placebo: 8 bladder cancer RR 1.32 (95% CI 0.40 to 4.61), adjusted HR 1.27 (95% CI 0.44 to 3.67) cases selenium: 8, placebo: 6 oesophageal cancer RR 0.33 (95% CI 0.03 to 1.84), adjusted HR 0.30 (95% CI 0.06 to 1.49) cases selenium: 2, placebo: 6 breast cancer RR 2.88 (95% CI 0.72 to 16.5), adjusted HR 2.95 (95% CI 0.80 to 10.9) cases selenium: 9, placebo:3 melanoma RR 0.97 (95% CI 0.32 to 2.96), adjusted HR 0.92 (95% CI 0.34 to 2.45) cases selenium: 8, placebo: 8 haematological cancer RR 1.58 (95% CI 0.46 to 6.14), adjusted HR 1.50 (95% CI 0.49 to 4.60) cases selenium: 8, placebo: 5 other specific carcinomas RR 0.55 (95% CI 0.14 to 1.82), adjusted HR 0.54 (95% CI 0.18 to 1.62), cases selenium: 5, placebo: 9 total carcinoma RR 0.55 (95% CI 0.40 to 0.77), adjusted HR 0.54 (95% CI 0.39 to 0.75), cases selenium: 59; placebo: 104 leukaemia /lymphomas RR 1.58 (95% CI 0.46 to 6.14), adjusted HR 1.50 (95% CI 0.49 to 4.60), cases selenium: 8, placebo 5 other specific non‐carcinomas RR 0.99 (95% CI 0.13 to 7.37), HR 0.99 (95% CI 0.20 to 4.94), cases selenium: 3, placebo: 3 total non‐carcinomas RR 1.17 (95% CI 0.57 to 2.44), adjusted HR 1.16 (95% CI 0.60 to 2.27), cases selenium: 19; placebo: 16 2) at the end of the blinded period (31 January 1996) (Duffield‐Lillico 2002): lung cancer RR 0.70 (95% CI 0.40 to 1.21), adjusted HR 0.74 (95% CI 0.44 to 1.24), cases selenium: 25, placebo: 35 prostate cancer RR 0.51 (95% CI 0.29 to 0.87), adjusted HR 0.48 (95% CI 0.28 to 0.80), cases selenium: 22, placebo: 42 colorectal cancer RR 0.46 (95% CI 0.19 to 1.08), adjusted HR 0.46 (95% CI 0.21 to 1.02), cases selenium: 9, placebo: 19 any cancer RR 0.75 (95% CI 0.58 to 0.98), adjusted HR 0.75 (95% CI 0.58 to 0.97), cases selenium: 105, placebo: 137 head and neck cancer RR 1.27 (95% CI 0.42 to 4.01), adjusted HR 1.27 (95% CI 0.47 to 3.42), cases selenium: 9, placebo: 7 bladder cancer RR 1.24 (95% CI 0.44 to 3.61), adjusted HR 1.28 (95% CI 0.50 to 3.25), cases selenium: 10, placebo: 8 oesophageal cancer RR 0.39 (95% CI 0.04 to 2.41), adjusted HR 0.40 (95% CI 0.08 to 2.07), cases selenium: 2, placebo: 5 breast cancer RR 1.82 (95% CI 0.62 to 6.01), adjusted HR 1.89 (95% CI 0.69 to 5.14), cases selenium: 11, placebo: 6 melanoma RR 1.21 (95% CI 0.46 to 3.30), adjusted HR 1.18 (95% CI 0.49 to 2.85), cases selenium: 11, placebo: 9 haematological cancer (lymphoma and leukaemia) RR 1.32 (95% CI 0.40 to 4.61), adjusted HR 1.25 (95% CI 0.43 to 3.61), cases selenium: 8, placebo: 6 cancer mortality, all sites RR 0.59 (95% CI 0.39 to 0.89), adjusted HR 0.59 (95% CI 0.39 to 0.87), cases selenium: 40, placebo: 66 other carcinomas RR 0.66 (95% CI 0.19 to 2.07), adjusted HR 0.67 (95% CI 0.24 to 1.88), cases selenium: 6, placebo:9 other non‐carcinomas RR 0.59 (95% CI 0.09 to 3.04), adjusted HR 0.59 (95% CI 0.14 to 2.47), cases selenium: 3, placebo: 5 |
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| Selenium levels in exposure categories | d.n.a. | |
| Notes | Adverse effects: Clark 1996: 35 participants (21 in selenium and 14 in control group) complained of adverse effects, mostly involving gastrointestinal upset, and withdrew treatment. Post‐hoc introduced secondary outcomes were: all‐cause mortality, total cancer mortality, total cancer incidence and incidence of lung / prostate / colorectal cancers HR: adjusted for sex, age, smoking status, clinic site, plasma selenium concentration, clinical sun damage, sunscreen use at baseline and number of BCCs/SCCs/NMSCs in the 12 months before randomisation |
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