Prostate Cancer
Conditions
Keywords
prostate cancer
Brief summary
RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development of cancer. It is not yet known which regimen of selenium and/or vitamin E may be more effective in preventing prostate cancer. PURPOSE: Randomized phase III trial to determine the effectiveness of selenium and vitamin E, either alone or together, in preventing prostate cancer.
Detailed description
OBJECTIVES: * Compare the effect of selenium and vitamin E administered alone vs in combination on the clinical incidence of prostate cancer. * Compare the effect of these prevention regimens on the incidence of lung cancer, colorectal cancer, and all cancers combined in participants on this study. * Compare the effect of these prevention regimens on prostate cancer-free survival, lung cancer-free survival, colorectal cancer-free survival, cancer-free survival, overall survival, and serious cardiovascular events in these participants.
Interventions
DRUGVitamin E
400 IU daily by mouth for 7-12 years
DRUGSelenium
200 mcg daily for 7-12 years
OTHERVitamin E placebo
daily for 7-12 years
OTHERselenium placebo
daily for 7-12 years
Sponsors
National Cancer Institute (NCI)
Eastern Cooperative Oncology Group
Cancer and Leukemia Group B
NCIC Clinical Trials Group
SWOG Cancer Research Network
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
50 Years to 120 Years
Healthy volunteers
Yes
Inclusion criteria
DISEASE CHARACTERISTICS: * Healthy male volunteers * Digital rectal examination (DRE) deemed not suspicious for prostate cancer performed within 364 days prior to study entry * Participants with a suspicious DRE are ineligible even if a recent or subsequent biopsy is negative for cancer * Total prostate-specific antigen ≤ 4.0 ng/mL within 364 days prior to study entry * No prior prostate cancer or high-grade (grade 2-3) prostatic intraepithelial neoplasia PATIENT CHARACTERISTICS: Age: * See Disease Characteristics Performance status: * Not specified Life expectancy: * Not specified Hematopoietic: * Not specified Hepatic: * Not specified Renal: * Not specified Cardiovascular: * Systolic blood pressure \< 160 mm Hg * Diastolic blood pressure \< 90 mm Hg * No history of hemorrhagic stroke Other: * No malignancies within the past 5 years except basal cell or squamous cell skin cancer * No uncontrolled medical illness * No retinitis pigmentosa PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * Not specified Endocrine therapy * Not specified Radiotherapy * Not specified Surgery * Not specified Other * At least 7 years since prior randomization to SWOG-9217, with completion of end-of-study biopsy requirement * No additional concurrent selenium or vitamin E (contained in individual supplements, antioxidant mix, or multivitamin) * Concurrent multivitamins allowed (supplied on study) * No concurrent anticoagulation therapy (e.g., warfarin) * Concurrent prophylactic aspirin (average daily dose no greater than 175 mg/day) allowed * Concurrent daily aspirin dose ≤ 81 mg for participants receiving clopidogrel * Concurrent anti-hypertension medication allowed * No concurrent participation in another study involving a medical, surgical, nutritional, or life-style intervention (unless no longer receiving the intervention and are in the follow-up phase only)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Prostate Cancer | Every six months for 7 to 12 years depending on when the participant was randomized. | Participants are seen at the study site every six month for an update of medical events. Prostate cancer diagnosis is based on participant report followed by the submission of a pathologic sample to central pathology review for confirmation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Lung Cancer | Participants are assessed for medical every six months for 7 to 12 years depending on when he was randomized . Upon diagnosis of prostate cancer, updates are annual. | Participants are seen at the study site every six month for an update of medical events. Cancer diagnoses are based on participant report. Medical records for non-prostate cancers were collected but they were not pathologically confirmed. If the participant has been diagnosed with prostate cancer, study site visits are once a year. Follow-up was planned for seven to 12 years depending on when the participant was randomized. |
| Number of Participants With Colorectal Cancer | Participants are assessed for medical every six months for 7 to 12 years depending on when he was randomized . Upon diagnosis of prostate cancer, updates are annual. | Participants are seen at the study site every six month for an update of medical events. Cancer diagnoses are based on participant report. Medical records for non-prostate cancers were collected but they were not pathologically confirmed. If the participant has been diagnosed with prostate cancer, study site visits are once a year. Follow-up was planned for seven to 12 years depending on when the participant was randomized. |
| Number of Participants With Any Diagnosis of Cancer | Participants are assessed for medical every six months for 7 to 12 years depending on when he was randomized . Upon diagnosis of prostate cancer, updates are annual. | Participants are seen at the study site every six month for an update of medical events. Cancer diagnoses are based on participant report. Medical records for non-prostate cancers were collected but they were not pathologically confirmed. If the participant has been diagnosed with prostate cancer, study site visits are once a year. Follow-up was planned for seven to 12 years depending on when the participant was randomized. |
| Prostate Cancer Free Survival; Lung Cancer-free Survival, Colorectal Cancer-free Survival, Cancer-free Survival, Overall Survival | Participants are assessed for medical every six months for 7 to 12 years depending on when he was randomized . Upon diagnosis of prostate cancer, updates are annual. | Participants are seen at the study site every six month for an update of medical events. If the participant has been diagnosed with prostate cancer, study site visits are once a year. Prostate cancer diagnosis is based on participant report followed by the submission of a pathologic sample to central pathology review for confirmation. Other cancer diagnoses are based on participant report. Medical records for non-prostate cancers were collected but they were not pathologically confirmed. Follow-up was planned for seven to 12 years depending on when the participant was randomized. |
| Number of Participants With Serious Cardiovascular Events | Participants are assessed for medical every six months for 7 to 12 years depending on when he was randomized . Upon diagnosis of prostate cancer, updates are annual. | Participants are seen at the study site every six month for an update of medical events. If the participant has been diagnosed with prostate cancer, study site visits are once a year. Cardiovascular events are based on self-report and are not confirmed. Follow-up was planned for seven to 12 years depending on when the participant was randomized. |
Countries
United States
Participant flow
Recruitment details
Men were randomized at 427 study sites in the US, Puerto Rico and Canada between August 22, 2001 and June 24, 2004.
Pre-assignment details
Prior to randomization, there was a three month formal pre-randomization period with no placebo run-in capsules to give potential participants to decide if they would agree to stop disallowed over-the-counter supplements of selenium or vitamin E. By returning for randomization, they exhibited their willingness to adhere to the trial.
Participants by arm
| Arm | Count |
|---|---|
| Vitamin E Vitamin E + matching placebo for selenium | 8,737 |
| Selenium Selenium + matching placebo for vitamin E | 8,752 |
| Combination Vitamin E + selenium | 8,703 |
| Placebo Matching placebo for vitamin E + matching placebo for selenium | 8,696 |
| Total | 34,888 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Ineligible | 11 | 3 | 5 | 5 |
| Overall Study | Poor data/ppt mgmt, regulatory problems | 156 | 155 | 155 | 155 |
Baseline characteristics
| Characteristic | Total | Vitamin E | Selenium | Combination | Placebo |
|---|---|---|---|---|---|
| Age (categorical) 50 - 54 years | 1479 participants | 402 participants | 337 participants | 385 participants | 355 participants |
| Age (categorical) 55 - 64 years | 20349 participants | 5143 participants | 5076 participants | 5052 participants | 5078 participants |
| Age (categorical) 65 - 74 years | 10807 participants | 2641 participants | 2733 participants | 2731 participants | 2702 participants |
| Age (categorical) >= 75 years | 2253 participants | 551 participants | 606 participants | 535 participants | 561 participants |
| Age, Continuous | 62.3 years | 62.4 years | 62.6 years | 62.3 years | 62.6 years |
| Education (highest) >= College graduate | 17513 Participant | 4394 Participant | 4430 Participant | 4372 Participant | 4317 Participant |
| Education (highest) <= High school graduate or GED | 7683 Participant | 1875 Participant | 1917 Participant | 1898 Participant | 1993 Participant |
| Education (highest) Some college/vocational school | 9353 Participant | 2387 Participant | 2327 Participant | 2348 Participant | 2291 Participant |
| Education (highest) Unknown/missing | 339 Participant | 81 Participant | 78 Participant | 85 Participant | 95 Participant |
| PSA (ng/ml) 0.1 - 1.0 | 16761 Participant | 4208 Participant | 4218 Participant | 4213 Participant | 4122 Participant |
| PSA (ng/ml) 1.1 - 2.0 | 10708 Participant | 2653 Participant | 2661 Participant | 2666 Participant | 2728 Participant |
| PSA (ng/ml) 2.1 - 3.0 | 4756 Participant | 1228 Participant | 1211 Participant | 1149 Participant | 1168 Participant |
| PSA (ng/ml) 3.1 - 4.0 | 2611 Participant | 634 Participant | 652 Participant | 659 Participant | 666 Participant |
| PSA (ng/ml) > 4.0 | 11 Participant | 3 Participant | 2 Participant | 1 Participant | 5 Participant |
| PSA (ng/ml) Unknown/missing | 41 Participant | 11 Participant | 8 Participant | 15 Participant | 7 Participant |
| Race/Ethnicity, Customized African American | 4314 Participant | 1107 Participant | 1053 Participant | 1076 Participant | 1078 Participant |
| Race/Ethnicity, Customized Hispanic (African American) | 360 Participant | 103 Participant | 86 Participant | 95 Participant | 76 Participant |
| Race/Ethnicity, Customized Hispanic (non-African American) | 1934 Participant | 477 Participant | 481 Participant | 484 Participant | 492 Participant |
| Race/Ethnicity, Customized Other | 711 Participant | 160 Participant | 190 Participant | 174 Participant | 187 Participant |
| Race/Ethnicity, Customized White | 27569 Participant | 6890 Participant | 6942 Participant | 6874 Participant | 6863 Participant |
| Region of Enrollment Canada | 3639 participants | 909 participants | 915 participants | 911 participants | 904 participants |
| Region of Enrollment Puerto Rico | 1460 participants | 365 participants | 366 participants | 365 participants | 364 participants |
| Region of Enrollment United States | 29789 participants | 7463 participants | 7471 participants | 7427 participants | 7428 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 34888 Participants | 8737 Participants | 8752 Participants | 8703 Participants | 8696 Participants |
| Smoking status Current | 2615 Participant | 659 Participant | 631 Participant | 670 Participant | 655 Participant |
| Smoking status Ever (unknown status) | 235 Participant | 55 Participant | 61 Participant | 56 Participant | 63 Participant |
| Smoking status Former | 16858 Participant | 4194 Participant | 4214 Participant | 4242 Participant | 4208 Participant |
| Smoking status Never | 14880 Participant | 3752 Participant | 3780 Participant | 3666 Participant | 3682 Participant |
| Smoking status Unknown | 300 Participant | 77 Participant | 66 Participant | 69 Participant | 88 Participant |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2,605 / 8,752 | 2,550 / 8,702 | 2,421 / 8,696 | 2,553 / 8,737 |
| serious Total, serious adverse events | 96 / 8,752 | 93 / 8,702 | 108 / 8,696 | 99 / 8,737 |
Outcome results
Primary
Number of Participants With Prostate Cancer
Participants are seen at the study site every six month for an update of medical events. Prostate cancer diagnosis is based on participant report followed by the submission of a pathologic sample to central pathology review for confirmation.
Time frame: Every six months for 7 to 12 years depending on when the participant was randomized.
Population: All randomized eligible men not at 2 sites for which the DSMC said the data could not be used due to participant and data management issues as well as regulatory problems.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vitamin E | Number of Participants With Prostate Cancer | 473 participants |
| Selenium | Number of Participants With Prostate Cancer | 432 participants |
| Combination | Number of Participants With Prostate Cancer | 437 participants |
| Placebo | Number of Participants With Prostate Cancer | 416 participants |
Comparison: Per study design, with a sample size of 32,400 men, using a 1-sided alpha=.005 level (equivalent to a 2-sided alpha=.01 level) there was 96% power to detect a 25% reduction in prostate cancer for either agent vs. Placebo.p-value: <0.0199% CI: [0.95, 1.35]Regression, Cox
Comparison: Per study design, with a sample size of 32,400 men, using a 1-sided alpha=.005 level (equivalent to a 2-sided alpha=.01 level) there was 96% power to detect a 25% reduction in prostate cancer for either agent vs. Placebo.p-value: <0.0199% CI: [0.87, 1.24]Regression, Cox
Comparison: Per study design, with a sample size of 32,400 men, using a 1-sided alpha=.005 level (equivalent to a 2-sided alpha=.01 level) there was 99% power to detect a 44% reduction in prostate cancer for combination vs. Placebo.p-value: <0.0199% CI: [0.88, 1.25]Regression, Cox
Secondary
Number of Participants With Any Diagnosis of Cancer
Participants are seen at the study site every six month for an update of medical events. Cancer diagnoses are based on participant report. Medical records for non-prostate cancers were collected but they were not pathologically confirmed. If the participant has been diagnosed with prostate cancer, study site visits are once a year. Follow-up was planned for seven to 12 years depending on when the participant was randomized.
Time frame: Participants are assessed for medical every six months for 7 to 12 years depending on when he was randomized . Upon diagnosis of prostate cancer, updates are annual.
Population: All randomized eligible participants excluding all men from 2 study sites that the DSMC said to exclude due to poor participant/data management and regulatory issues.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vitamin E | Number of Participants With Any Diagnosis of Cancer | 856 participants |
| Selenium | Number of Participants With Any Diagnosis of Cancer | 837 participants |
| Combination | Number of Participants With Any Diagnosis of Cancer | 846 participants |
| Placebo | Number of Participants With Any Diagnosis of Cancer | 824 participants |
Comparison: The power to look at all cancer incidence is greater than 90%.p-value: >0.0599% CI: [0.91, 1.17]Regression, Cox
Comparison: The power to look at all cancer incidence is greater than 90%.p-value: >0.0599% CI: [0.89, 1.15]Regression, Cox
Comparison: The power to look at all cancer incidence is greater than 90%.p-value: >0.0599% CI: [0.9, 1.16]Regression, Cox
Secondary
Number of Participants With Colorectal Cancer
Participants are seen at the study site every six month for an update of medical events. Cancer diagnoses are based on participant report. Medical records for non-prostate cancers were collected but they were not pathologically confirmed. If the participant has been diagnosed with prostate cancer, study site visits are once a year. Follow-up was planned for seven to 12 years depending on when the participant was randomized.
Time frame: Participants are assessed for medical every six months for 7 to 12 years depending on when he was randomized . Upon diagnosis of prostate cancer, updates are annual.
Population: All randomized eligible participants excluding all men from 2 study sites that the DSMC said to exclude due to poor participant/data management and regulatory issues.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vitamin E | Number of Participants With Colorectal Cancer | 66 participants |
| Selenium | Number of Participants With Colorectal Cancer | 63 participants |
| Combination | Number of Participants With Colorectal Cancer | 77 participants |
| Placebo | Number of Participants With Colorectal Cancer | 60 participants |
Comparison: The trial was designed to study prostate cancer and colorectal cancer has a lower incidence rate, there was limited power to look at colorectal cancer incidence.p-value: >0.0599% CI: [0.69, 1.73]Regression, Cox
Comparison: The trial was designed to study prostate cancer and colorectal cancer has a lower incidence rate, there was limited power to look at colorectal cancer incidence.p-value: >0.0599% CI: [0.66, 1.67]Regression, Cox
Comparison: The trial was designed to study prostate cancer and colorectal cancer has a lower incidence rate, there was limited power to look at colorectal cancer incidence.p-value: >0.0599% CI: [0.82, 2]Regression, Cox
Secondary
Number of Participants With Lung Cancer
Participants are seen at the study site every six month for an update of medical events. Cancer diagnoses are based on participant report. Medical records for non-prostate cancers were collected but they were not pathologically confirmed. If the participant has been diagnosed with prostate cancer, study site visits are once a year. Follow-up was planned for seven to 12 years depending on when the participant was randomized.
Time frame: Participants are assessed for medical every six months for 7 to 12 years depending on when he was randomized . Upon diagnosis of prostate cancer, updates are annual.
Population: All randomized eligible participants excluding all men from 2 study sites that the DSMC said to exclude due to poor participant/data management and regulatory issues.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vitamin E | Number of Participants With Lung Cancer | 67 participants |
| Selenium | Number of Participants With Lung Cancer | 75 participants |
| Combination | Number of Participants With Lung Cancer | 78 participants |
| Placebo | Number of Participants With Lung Cancer | 67 participants |
p-value: >0.0599% CI: [0.64, 1.55]Regression, Cox
p-value: >0.0199% CI: [0.73, 1.72]Regression, Cox
p-value: >0.0199% CI: [0.9, 1.16]Regression, Cox
Secondary
Number of Participants With Serious Cardiovascular Events
Participants are seen at the study site every six month for an update of medical events. If the participant has been diagnosed with prostate cancer, study site visits are once a year. Cardiovascular events are based on self-report and are not confirmed. Follow-up was planned for seven to 12 years depending on when the participant was randomized.
Time frame: Participants are assessed for medical every six months for 7 to 12 years depending on when he was randomized . Upon diagnosis of prostate cancer, updates are annual.
Population: All randomized eligible participants excluding all men from 2 study sites that the DSMC said to exclude due to poor participant/data management and regulatory issues.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vitamin E | Number of Participants With Serious Cardiovascular Events | 1034 participants |
| Selenium | Number of Participants With Serious Cardiovascular Events | 1080 participants |
| Combination | Number of Participants With Serious Cardiovascular Events | 1041 participants |
| Placebo | Number of Participants With Serious Cardiovascular Events | 1050 participants |
p-value: >0.0599% CI: [0.88, 1.09]Chi-squared
p-value: >0.0599% CI: [0.92, 1.13]Chi-squared
p-value: >0.0599% CI: [0.89, 1.1]Chi-squared
Secondary
Prostate Cancer Free Survival; Lung Cancer-free Survival, Colorectal Cancer-free Survival, Cancer-free Survival, Overall Survival
Participants are seen at the study site every six month for an update of medical events. If the participant has been diagnosed with prostate cancer, study site visits are once a year. Prostate cancer diagnosis is based on participant report followed by the submission of a pathologic sample to central pathology review for confirmation. Other cancer diagnoses are based on participant report. Medical records for non-prostate cancers were collected but they were not pathologically confirmed. Follow-up was planned for seven to 12 years depending on when the participant was randomized.
Time frame: Participants are assessed for medical every six months for 7 to 12 years depending on when he was randomized . Upon diagnosis of prostate cancer, updates are annual.
Population: All randomized eligible participants excluding all men from 2 study sites that the DSMC said to exclude due to poor participant/data management and regulatory issues. Deaths include those reported as SAEs as well as non-SAE deaths as this was a prevention trial with older generally healthy men at baseline who were followed for a long time.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vitamin E | Prostate Cancer Free Survival; Lung Cancer-free Survival, Colorectal Cancer-free Survival, Cancer-free Survival, Overall Survival | Lung cancer deaths | 38 participants |
| Vitamin E | Prostate Cancer Free Survival; Lung Cancer-free Survival, Colorectal Cancer-free Survival, Cancer-free Survival, Overall Survival | All cancer deaths | 106 participants |
| Vitamin E | Prostate Cancer Free Survival; Lung Cancer-free Survival, Colorectal Cancer-free Survival, Cancer-free Survival, Overall Survival | Colorectal cancer deaths | 13 participants |
| Vitamin E | Prostate Cancer Free Survival; Lung Cancer-free Survival, Colorectal Cancer-free Survival, Cancer-free Survival, Overall Survival | Prostate cancer deaths | 0 participants |
| Vitamin E | Prostate Cancer Free Survival; Lung Cancer-free Survival, Colorectal Cancer-free Survival, Cancer-free Survival, Overall Survival | All deaths | 358 participants |
| Selenium | Prostate Cancer Free Survival; Lung Cancer-free Survival, Colorectal Cancer-free Survival, Cancer-free Survival, Overall Survival | Prostate cancer deaths | 1 participants |
| Selenium | Prostate Cancer Free Survival; Lung Cancer-free Survival, Colorectal Cancer-free Survival, Cancer-free Survival, Overall Survival | Lung cancer deaths | 45 participants |
| Selenium | Prostate Cancer Free Survival; Lung Cancer-free Survival, Colorectal Cancer-free Survival, Cancer-free Survival, Overall Survival | Colorectal cancer deaths | 10 participants |
| Selenium | Prostate Cancer Free Survival; Lung Cancer-free Survival, Colorectal Cancer-free Survival, Cancer-free Survival, Overall Survival | All cancer deaths | 128 participants |
| Selenium | Prostate Cancer Free Survival; Lung Cancer-free Survival, Colorectal Cancer-free Survival, Cancer-free Survival, Overall Survival | All deaths | 378 participants |
| Combination | Prostate Cancer Free Survival; Lung Cancer-free Survival, Colorectal Cancer-free Survival, Cancer-free Survival, Overall Survival | Prostate cancer deaths | 0 participants |
| Combination | Prostate Cancer Free Survival; Lung Cancer-free Survival, Colorectal Cancer-free Survival, Cancer-free Survival, Overall Survival | All deaths | 359 participants |
| Combination | Prostate Cancer Free Survival; Lung Cancer-free Survival, Colorectal Cancer-free Survival, Cancer-free Survival, Overall Survival | All cancer deaths | 117 participants |
| Combination | Prostate Cancer Free Survival; Lung Cancer-free Survival, Colorectal Cancer-free Survival, Cancer-free Survival, Overall Survival | Lung cancer deaths | 39 participants |
| Combination | Prostate Cancer Free Survival; Lung Cancer-free Survival, Colorectal Cancer-free Survival, Cancer-free Survival, Overall Survival | Colorectal cancer deaths | 15 participants |
| Placebo | Prostate Cancer Free Survival; Lung Cancer-free Survival, Colorectal Cancer-free Survival, Cancer-free Survival, Overall Survival | Lung cancer deaths | 41 participants |
| Placebo | Prostate Cancer Free Survival; Lung Cancer-free Survival, Colorectal Cancer-free Survival, Cancer-free Survival, Overall Survival | All cancer deaths | 125 participants |
| Placebo | Prostate Cancer Free Survival; Lung Cancer-free Survival, Colorectal Cancer-free Survival, Cancer-free Survival, Overall Survival | All deaths | 382 participants |
| Placebo | Prostate Cancer Free Survival; Lung Cancer-free Survival, Colorectal Cancer-free Survival, Cancer-free Survival, Overall Survival | Prostate cancer deaths | 0 participants |
| Placebo | Prostate Cancer Free Survival; Lung Cancer-free Survival, Colorectal Cancer-free Survival, Cancer-free Survival, Overall Survival | Colorectal cancer deaths | 10 participants |
Comparison: Only results from overall survival are presented as the number of cancer-specific deaths is too few to be meaningful.p-value: >0.0599% CI: [0.77, 1.13]Regression, Cox
Comparison: Only results from overall survival are presented as the number of cancer-specific deaths is too few to be meaningful.p-value: >0.0599% CI: [0.82, 1.19]Regression, Cox
Comparison: Only results from overall survival are presented as the number of cancer-specific deaths is too few to be meaningful.p-value: >0.0599% CI: [0.77, 1.13]Regression, Cox