ONC: Chemotherapy (2006)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
To study the effect of selenium in reducing the toxicity of cisplatin in cancer patients.
Inclusion Criteria:

Cancer diagnosed by pathology or cytology

Exclusion Criteria:
None noted
Description of Study Protocol:

Recruitment :Not described

 

Design:Subjects were randomized into group A with selenium administration in first chemotherapy cycle as study cases and without selenium in the second cycle of chemotherapy as control.  Subjects randomized to Group B had no selenium in the first chemotherapy cycle as control and received selenium in the second chemotherapy cycle as study cases.

 

Blinding used:Not described

 

Intervention: 4000 micrograms selenium/day as Seleno-Kappacarrageenan given from 4 before to 4 days after chemotherapy for study cases.

 

Data Collection Summary:

Timing of Measurements

  • Serum selenium: 4 days before and 4 days after selenium administration
  • Liver Function: SGPT, bilirubin, AKP measured on days 4 and 8 before and post selenium supplementation
  • Renal Toxicity:
    • BUN and creatinine on days 4 and 8 before and after selenium administration
    • Urine enzymes (NAG, GGT, LAP, AAP, ALP) 2, 24, 48, 72 hours before and after chemotherapy
  • Hematology: Peripheral WBC, platelet and RBC counts 7,10,14, 20 days before and after chemotherapy.

 

Dependent Variables

  • Selenium-associated side effects of cisplatin: liver and renal toxicity measures
  • Bone marrow suppression: peripheral WBC, blood transfusion and consumption of granulocyte colony stimulationg factors

Independent Variables

  • Selenium supplementation: serum selenium levels  
Description of Actual Data Sample:

 

Initial N: Selenium supplemented group = 41. Group A: 20, first cycle of chemotherapy with selenium administration.  Group B: 21, second cycle of chemotherapy.  Controls = 41.  Group A: 20, without selenium supplementation in second cycle of chemotherapy. Group B: 21, without selenium supplementation in first cycle of chemotherapy. 

  • Male: female 27:14

Age: 31-72 years

 

Other relevant demographics:

  • Lung cancer 27
  • Epidermoid carcinoma 10
  • Adenocarcinoma 10
  • Gastric carcinoma 2
  • Primary liver cancer 2
  • Esophagus carcinoma 2
  • Colon carcinoma 1

Karnofsy performance status scale for each patients was >60.

Chemotherapy: cisplatin was administered by IV in dosage of 60-80 mg/M2 on day 1 in combination chemotherapy.

 

Location: Beijing Hospital, Beijing China

 

Summary of Results:

 Only statistically significant differences are reported here.

Variables

Treatment Group

Measures and confidence intervals

Control group

Measures and confidence intervals

Statistical Significance of Group Difference

Renal toxicity

Urine NAG 2, 24, 48 hours after chemotherapy

Urine GGT 2,24,48 hours after chemotherapy

Urine AAP 2,24,48,72 hours after chemotherapy

 

9.56+8.71, 9.52+6.85,8.19+5.21

 

18.88+12.04, 17.18+8.42, 18.89+7.92

13.94+8.08, 14.65+11.79, 13.43+8.59,13.39+9.54

 

16.24+7.33, 13.59+6.58, 13.10+9.86

41.38+21.30, 27.24+12.72, 23.59+10.51

24.05+13.69, 24.25+14.52, 18.92+10.09,20.77+14.32

 

P<0.005, <0.05, <0.01

 

P<0.05, <0.001, <0.02

P<0.001, <0.01, <0.02, <0.05

Bone marrow suppression:

Peripheral WBC, day 14

Blood transfusion, average volume (mL)

Consumption of granulocyte colony stimulating factor (IU)

 

3.35+2.01

 

0

110+82

 

2.31+1.38

 

62 +38

723+192

 

P<0.05

 

P<0.05

P<0.05

 

 

Author Conclusion:
"Our study suggested that co-administration of selenium could reduce the nephrotoxicity and bone marrow suppression induced by cisplatin-contained chemotherapy, possiby resulting in a higher therapeutic index and indicating a potential increase in the utilization of cisplatin in clinical cancer chemotherapy. Of course, the optimal dosage of selenium as a chemoprotector of cisplatin and high dosage of cisplatin with selenium in treatement of cancer need to be further studied."
Funding Source:
Government: Ministry of Public Health (China)
Reviewer Comments:
Valuable study in that various cancer types were studied.  Change in Karnofsky index was not reported so that limits the ability to evaulate "therapeutic index". 
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
  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
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
 
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
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
  2.2. Were criteria applied equally to all study groups? 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? Yes
3. Were study groups comparable? N/A
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) No
  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
  3.4. 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
  3.6. 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
  4.1. 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
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? N/A
  4.4. Were reasons for withdrawals similar across groups? N/A
  4.5. 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? ???
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? ???
  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
  5.4. 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
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
  6.2. 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? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? Yes
  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
  6.8. 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
  7.1. Were primary and secondary endpoints described and relevant to the question? N/A
  7.2. Were nutrition measures appropriate to question and outcomes of concern? N/A
  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
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? ???
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. 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
  8.3. 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
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? N/A
  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
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? N/A
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes