EAL

ONC: Chemotherapy (2006)

Citation:

Sieja K, Talerczyk M. Selenium as an element in the treatment of ovarian cancer in women receiving chemotherapy. Gynecol Oncol. 2004 May;93(2):320-7.

PubMed ID: 15099940

Study Design:

Randomized Controlled Trial

Class:

A - Click here for explanation of classification scheme.

Quality Rating:

POSITIVE: See Quality Criteria Checklist below.

Research Purpose:

"...to examine how selenium supplementation infulences oxidative stress (malondialdehyde) and the gutathione peroxidase system in patients with ovarian cancer undergoing chemotherapy."

Inclusion Criteria:

Patients with diagnosis of ovarian cancer established by laparotomy and histopathological examination of tumor samples
No accompanying organic or systemic diseases
Provided verbal and written informed consent

Exclusion Criteria:

No additional factors noted

Description of Study Protocol:

Recruitment : Not described

Design : After randomization study patients received chemotherapy plus selenium supplementation during 3 months of chemotherapy cycles given in 21 day cycles. Control patients received the same chemotherapy protocol and a selenium-free placebo. No other vitamins or microelecments were given and granulocyte colony stimulator factor was not administered.

Blinding used (if applicable): Double blind

Intervention (if applicable):

Study group
- 2 capsules x 4/day/3 month of Protecton Zellactive (Smith Kline Beecham, Fink Naturaznei GmbH, Germany).
  - 2 capsules = Beta-carotene 15 mg; vitamin C 200 mg; vitamin E 36 mg, riboflavin 4.5 g, niacin 45 mg, selenium yeast 50 mg (= 50 micrograms selenium)
Control group received a placebo that contained all of the components of the study capsules except for selenium

Statistical Analysis

Outcome of teatment in time was analyzed by ANOVA for repeated measure desgin. Tukey's test (test post hoc) was used when significant interactions were found. Due to asymmetry of distrbution for marker CA-25, logarithmical conversicon was applied. For all comparisons, the level of significance was P < 0.05.

Data Collection Summary:

Timing of Measurements

Clinical status was checked 1x/month with
- standard gynecological examination
- ultrasound of the abdomen and small pelvis
- biochemistries
Before and after the chemotherapy cycle
- body weight was assessed
- systolic and diastolic blood pressure were measured
After each chemotherapy cycle
- hematology, platelet count, urea, creatinine, bilirubin, aminotransferases activities and cancer antigen, CA-125, were measured
- chemotherapy side effects assessed
These parameters were measured 4,8, and 12 weeks after the administration of chemotherapy and supplementation of selenium had begun
- hair and serum concentration of selenium
- activity of glutatione peroxidase system (GSH-P_x)
- concentration of malondialdehyde (MDA)

Dependent Variables

Oxidative stress via concentration of malondialdehyde (MDA)
Activity of glutatione peroxidase system (GSH-P_x)
Chemotherapy side effects:
- Semi-quantitative 4-point scale
- ECOG toxicity criteria

Independent Variables

Protecton Zellactive capsules

Control Variables

hair and serum concentration of selenium

Description of Actual Data Sample:

Initial N: Study and control groups both had 31 patients with ovarian cancer undergoing chemotherapy

Age: Study group 49.4 + 12.9 y, control group 52.7 + 12.6 y

Ethnicity: unknown

Other relevant demographics: All patients were treated to the accepted clinical protocol for ovarian cancer: surgery was followed by IV multi-grug tchemotherapy cycles in 21 day intervals. Chemotheapy was cysplatin 100 mg/m² and cyclophasphamide 600 mg/m²

Study group diagnoses were: mucinous cancer 15 cases; serous papillary cancer 15; dysgerminoma 1. 15 were stage I/II and 16 were III/IV.

Control group diagnoses were: mucinous cancer 11 cases; serous papillary cancer 17; clear cell carcinoma 2; endometrioid epithelial cell cancer 1. 16 were stage I/II and 15 were III/IV.

Anthropometrics: Study group average body weight was 66.0 +12/ kg, control group 65.5 + 12.7 kg.

Location: Pomeranian Medical Academy, Szxzecin, Poland.

Summary of Results:

Only statistically significant results are reported.

Variables

Treatment Group

Measures and confidence intervals

Control group

Measures and confidence intervals

Statistical Significance of Group Difference

Oxidative stress (MDA)

--MDA in serum nmol/mL² [nmol MDA/10^-9 platelets]

Month 1

Month 2

Month 3

3.91+1.73 [5.48+4.8]

4.43+1.56 [6.84+4.37]

4.81+1.59 [6.04+4.01]

5.29+2.27 [6.22+5.17]

5.78+2.36 [5.77+4.02]

4.94+2.95 [4.77+3.25]

ANOVA P=0.0542; tukey's t-test P=0.0363; 0.0489

[ANOVA P=0.0168; tukey's t- test P=0.0477;0.2516]

Activity of glutatione peroxidase system GSH-P_x in erythrocytes (micromoles oxidized NADPH/min/g Hb)

Month 1

Month 2

Month 3

6.4+2.95

8.14+3.59

10.11+4.30

6.57+2.27

6.88+2.45

6.71+3.65

ANOVA P=0.0014; tukey's t-test P=0.0015; 0.0038

Side effects of chemotherapy

nausea

vomiting

diarrhea

stomatitis

hair loss

flatulence

abdominal pain

weakness

malaise

loss of appetite

Significant decrease in all cited side effects ecept diarrhea (p<0.5). Selenium supplementation reduced frequency of complaints after 2 and 3 months

nausea (p<0.000 after 2 months,p<0.0000 after 3 months)

vomiting (p<0.000 after 3 months)

stomatitis (p<0.0292 after 3 months)

hair loss (p<0.000 after 2 months, p<0.0392 after 3 months)

flatulence (p<0.0003 after 2 months, p<0.0000 after 3 months)

abdominal pain (p<0.006 after 2 months, p<0.0202 after 3 months)

weakness (p<0.0001 after 2 months, p<0.0000 after 3 months)

ill-being (p<0.0017 after 2 months, p<0.0000 after 3 months)

loss of appetite (p<0.0000 after 2 months and 3 months respectively)

Other Findings

Selenium supplementation sirgnificantly increased serum concentration (p<0.05) and hair (p<0.05)

Author Conclusion:

"1. Supplementation with selenium in the form of selenium-enriched yeast in patients with ovarian cancer undergoing chemotherapy leads to an increase in the concentration of this microelement in the organism, which activates selenium-dependent enzymes.

2. It has been stated that the effect of selenium on the decrease of adverse effects of ovarian cancer chemotherapy depends on the duration of the application of this microelement. Administering of selenium for 2 months reduces significantly the side effects of chemotherapy.

3. As a result of this clinical trial, we conclude that there are beneficial effects caused by ingesting selenium as a supportive element in chemotherapy."

Funding Source:

University/Hospital:

Pomeranian Academy of Medicine (Poland)

Reviewer Comments:

These very hopeful results cannot be generalized beyond this cancer and chemotherapy type. Nonetheless the results are exciting and research into other cancer types ands antineoplastic regimens are needed.

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
	1.	Was the research question clearly stated?	Yes
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
	1.3.	Were the target population and setting specified?	Yes
	2.	Was the selection of study subjects/patients free from bias?	???
2.	Was the selection of study subjects/patients free from bias?		???
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
	3.	Were study groups comparable?	Yes
3.	Were study groups comparable?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	Yes
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
	4.	Was method of handling withdrawals described?	N/A
4.	Was method of handling withdrawals described?		N/A
	4.1.	Were follow-up methods described and the same for all groups?	N/A
	4.1.	Were follow-up methods described and the same for all groups?	N/A
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	N/A
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	N/A
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	N/A
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	N/A
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
	5.	Was blinding used to prevent introduction of bias?	Yes
5.	Was blinding used to prevent introduction of bias?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	Yes
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	???
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	???
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
	6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?	Yes
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	N/A
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	N/A
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	N/A
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	N/A
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	N/A
	6.6.	Were extra or unplanned treatments described?	N/A
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	N/A
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
	7.	Were outcomes clearly defined and the measurements valid and reliable?	Yes
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	???
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	???
	7.7.	Were the measurements conducted consistently across groups?	Yes
	7.7.	Were the measurements conducted consistently across groups?	Yes
	8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	N/A
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	N/A
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	Yes
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	Yes
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
	9.	Are conclusions supported by results with biases and limitations taken into consideration?	Yes
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
	10.	Is bias due to study's funding or sponsorship unlikely?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes