Study Note
Brief summary
In this study, a large sample of 120 cancer patients who had received cisplatin chemotherapy was examined. Half of the patients received lycopene in addition to chemotherapy and standard treatment to prevent kidney damage. Neither the participants nor the study leaders knew who was also receiving lycopene. The values recorded to determine kidney toxicity tended to develop slightly better in the group of patients who also received lycopene than in the other group: urea values improved in the first week, but then rose again almost to the initial level. In the other group, the values continued to rise slightly directly from the initial level. There were no differences between the groups with regard to serum creatinine. And the glomerular filtration rate, the most accurate measure of kidney function, remained unchanged in the lycopene group, while it deteriorated in the other group. However, the effects are of a very small magnitude and are not significant in practice. A disadvantage of the study is that it is not described how many participants actually completed the study and how missing data was dealt with.
In dieser Studie wurde eine große Stichprobe von 120 Krebspatienten, die eine Cisplatin-Chemotherapie bekommen haben, untersucht. Die Hälfte der Patienten hat zusätzlich zur Chemotherapie und Standardbehandlung zur Prävention von Nierenschädigungen auch Lycopin bekommen. Weder die Teilnehmer noch die Studienleiter wussten, wer zusätzlich Lycopin bekommt. Die zur Bestimmung der Nierentoxizität erhobenen Werte entwickelten sich in der Gruppe der Patienten, die zusätzlich Lycopin bekommen haben, tendenziell etwas besser als in der anderen Gruppe: Werte des Harnstoffs verbesserten sich in der ersten Woche, stiegen dann aber fast aufs Ausgangsniveau wieder an. In der anderen Gruppe stiegen die Werte direkt vom Ausgangsniveau weiter leicht an. Hinsichtlich des Serumkreatinins gab es keine Unterschiede zwischen den Gruppen. Und die glomeruläre Filtrationsrate als genauestes Maß für die Nierenfunktion blieb in der Lycopin-Gruppe unverändert, während sie sich in der anderen Gruppe verschlechterte. Die Effekte sind allerdings in einer sehr geringen Größenordnung und sind in der Praxis nicht bedeutsam. Ein Nachteil der Studie ist, dass nicht beschrieben wird, wie viele Teilnehmer die Studie wirklich beendet haben und wie mit fehlenden Daten umgegangen wurde.
Study Design
| Prospective / Retrospective Prospective: forward-looking, examples include clinical trials, cohort studies, and long-term observational studies;</br>Retrospective: backward-looking, relying on existing data, examples include case-control studies and retrospective cohort studies
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Prospective
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| Monocentric / Multicentric Monocentric: conducted in one center/ hospital; </br>Multicentric: conducted in multiple centers/ hospitals
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Monocentric
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| Blinding No: Open, all parties are aware of group assignments;</br>Single: one party is unaware of group assignments (generally participants);</br>Double: two parties are unaware of group assignments (generally the participants and the researchers); </br>Triple: concealing group assignment from additional parties
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Double
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| Is randomized
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Yes
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| Cross-over Participants alternate between different treatment groups or conditions over a specified period, allowing each participant to serve as their own control
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No
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| Number of arms
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2
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Study characteristics
| Inclusion criteria
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Suffering cancer without primary involvement or renal metastasis; being candidate for administration of 70-100 mg/m2 cisplatin; 20-80 years old, creatinine (Cr)<1.5 mg/dL; normal hearing; no underlying nephropathy; performance status of 0-2 of Karnofsky
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| Exclusion criteria
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Allergy to lycopene; hearing loss; significant neuropathy; metastatic renal involvement
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| N randomized
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120
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| Analysis PP: Per Protocol analysis, i.e. only participants included who adhered to the study protocol.</br>ITT: Intention-to-treat analysis, i.e. all randomized participants included regardless of any drop-outs or changes in assignment.</br>mITT: modified Intention-to-treat analysis can refer to analyses in which participants with missing outcome data are excluded or it can refer to analyses in which only participants who received at least one treatment dose are included. In this case, participants dropped out of the study prematurely for reasons unrelated to the treatment.
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NI
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| Specifications on analyses
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The data were analyzed by SPSS 20 software. The quantitative variables were expressed as mean (standard deviation) or median (interquartile range) and qualitative variables as number (%). To compare quantitative variables, repeated measures analysis of variance (ANOVA) was used and to compare qualitative variables, chi-square
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| Countries of data collection
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Iran
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| LoE Level of evidence
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1b Oxford 2009
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| Outcome timeline Data collection times
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T1: start of the study
T2: day 7 of chemotherapy
T3: day 21 of chemotherapy
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Characteristics of participants
| Setting Refers to cancer therapy setting.</br>- Curative therapy: aims to completely eradicate a disease and achieve a full recovery; </br>- Neo-adjuvant therapy: form of curative therapy, given before the primary treatment for cancer (usually surgery); </br>- Adjuvant therapy: form of curative therapy, given after the primary treatment for cancer (usually surgery); </br>- Palliative therapy: focuses on providing relief from symptoms and improving the quality of life for patients, without necessarily targeting the underlying disease; </br>- Active surveillance: involves close monitoring of disease progression without any intervention (typically used for prostate cancer);</br>- No therapy setting: Patients who completed therapy/are currently not in cancer treatment, cancer survivors.
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NI
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| Types of cancer "Other Cancers" means that only a subpopulation was specified, but further unspecified cancer types were included
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NI
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| Cancer stages Early Stage: generally refers to cancer that is localized to the area where it started, mostly stages I and II;</br>Advanced Stage: cancer that has spread beyond its original site, mostly stages III and IV, with stage IV indicating distant metastasis
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NI
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| Specifications on cancer stages
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NA
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| Comorbidities
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NI
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| Current cancer therapies
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Chemotherapy
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| Specifications on cancer therapies
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Cisplatin-chemotherapy
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| Previous cancer therapies
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NI
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| Gender
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Mixed
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| Gender specifications
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Female n (%): 58 (48.3)
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| Age groups
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Adults (18+)
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| Age groups specification
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Age in years, mean (SD), range: 57.5 (12.65), 18-82
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Arms
| Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment
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Intervention
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| Number of participants (arm) N randomized
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60
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| Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date
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-999
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| Drop-out reasons
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NI
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| Intervention
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Lycopene
+ All participants received chemotherapy + standard treatment to prevent kidney damage (hydration + magnesium sulphate)
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| Dosage and regime
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Lycopene tablet (25 mg) each 12 hours from 24 hours before to 72 hours after chemotherapy (cisplatin administration)
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| One-time application
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No
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| Duration in days For long-term interventions, the number of days is an estimation.</br>A value of -999 indicates that the exact duration cannot be extracted from the study due to ambiguous or incomplete information. See Outcome timeline or Dosage and regime for further information.
|
4
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| Side effects / Interactions
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NI
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| Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment
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Passive control
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| Number of participants (arm) N randomized
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60
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| Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date
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-999
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| Drop-out reasons
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NI
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| Intervention
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+ All participants received chemotherapy + standard treatment to prevent kidney damage (hydration + magnesium sulphate)
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| Dosage and regime
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NA
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| One-time application
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No
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| Duration in days For long-term interventions, the number of days is an estimation.</br>A value of -999 indicates that the exact duration cannot be extracted from the study due to ambiguous or incomplete information. See Outcome timeline or Dosage and regime for further information.
|
4
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| Side effects / Interactions
|
NI
|
Outcomes
Toxicity
| Outcome type As specificed by the authors
|
NI
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| Outcome specification
|
Renal toxicity: urea mg/dL (start of the study, day 7 of chemotherapy, day 21 of chemotherapy)
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| Type of measurement
|
Blood Test
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| Results during intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".
|
NI
|
| Results after intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".
|
Mean (SD), p-value of the interaction between time and arm:
significantly different development of the arms; values in lycopene arm fall/improve considerably from start of the study to day 7, but then rise again almost to the initial level at day 21
Values in control arm tend to increase/decrease slightly
Lycopene arm start: 29.29 (9.25), day 7: 16.17 (8.97), day 21: 26.82 (9.27)
Control arm start: 26.62 (9.80), day 21: 25.55 (7.72), day 21: 30.74 (11.65), p<0.001, significant
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| Risk of Bias Assessment: Cochrane RoB tool 2.0
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| Bias arising from the randomization process
|
?
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| Bias due to deviation from intended intervention (assignment to intervention)
|
?
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| Bias due to deviation from intended intervention (adhering to intervention)
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NA
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| Bias due to missing outcome data
|
?
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| Bias in measurement of the outcome
|
?
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| Bias in selection of the reported result
|
?
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| Other sources of bias
|
?
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| Overall RoB judgment
|
?
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Toxicity
| Outcome type As specificed by the authors
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NI
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| Outcome specification
|
Renal toxicity: serum creatinine mg/dL (start of the study, day 7 of chemotherapy, day 21 of chemotherapy)
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| Type of measurement
|
Blood Test
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| Results during intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".
|
NI
|
| Results after intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".
|
Mean (SD), p-Wert of interaction between time and arm:
no significant differences in arms:
Lycopene arm start: 1.05 (0.23), day 7: 1.12 (0.65), day 21: 1.09 (0.42)
Control arm start: 1.00 (0.24), day 7: 1.00 (0.22), day 21: 1.17 (0.51), p=0.131, not significant
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| Risk of Bias Assessment: Cochrane RoB tool 2.0
|
| Bias arising from the randomization process
|
?
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| Bias due to deviation from intended intervention (assignment to intervention)
|
?
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| Bias due to deviation from intended intervention (adhering to intervention)
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NA
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| Bias due to missing outcome data
|
?
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| Bias in measurement of the outcome
|
?
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| Bias in selection of the reported result
|
?
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| Other sources of bias
|
?
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| Overall RoB judgment
|
?
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Toxicity
| Outcome type As specificed by the authors
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NI
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| Outcome specification
|
Renal toxicity: glomerular filtration rate cc/min (start of the study, day 7 of chemotherapy, day 21 of chemotherapy)
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| Type of measurement
|
Blood Test
|
| Results during intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".
|
NI
|
| Results after intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".
|
Mean (SD), p-Wert of interaction between time and arm:
significant different development in arms; values in lycopene arm tend to remain the same, values in control arm fall/get worse:
Lycopene arm start: 66.67 (18.75), day 7: 69.22 (20.28), day 21: 67.14 (20.10)
Control arm start: 72.06 (17.39), day 7: 71.92 (17.17), day 21: 65.01 (20.77), p=0.004, significant
|
| Risk of Bias Assessment: Cochrane RoB tool 2.0
|
| Bias arising from the randomization process
|
?
|
| Bias due to deviation from intended intervention (assignment to intervention)
|
?
|
| Bias due to deviation from intended intervention (adhering to intervention)
|
NA
|
| Bias due to missing outcome data
|
?
|
| Bias in measurement of the outcome
|
?
|
| Bias in selection of the reported result
|
?
|
| Other sources of bias
|
?
|
| Overall RoB judgment
|
?
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Funding and Conflicts of Interest
| Funding
|
Support from the Deputy of research and technology of Shahrekord University of Medical Sciences
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| Conflicts of Interest
|
According to authors no conflict of interest
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Further points for assessing the study
Sample
| Power analysis performed
|
?
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| - Sample size corresponds to power analysis
|
NI
|
| - Reasons for insufficient sample size based on power analysis
|
NI
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| If no power analysis performed: at least moderate sample size (n >= 30 per arm)
|
?
|
| Ethnicity mentioned
|
?
|
Alternative Explanation
| Other explanations for an effect besides the investigated intervention
|
NI
|
| - Possibility of attention effects
|
?
|
| - Possibility of placebo effects
|
?
|
| - Other reasons
|
?
|
Statistics
| Correct use of parametric and non-parametric tests Testing for normal distribution only necessary if parametric tests are used, NI: use of parametric tests without report of normal distribution testing
|
NI
|
| Correction for multiple testing
|
?
|
| Measurement of compliance
|
?
|
| Consistent reporting in numbers (figures, flowchart, abstract, results)
|
?
|
| Comprehensive and coherent reporting
|
?
|
| Cross-over
|
NI
|
| - Sufficient washout period
|
?
|
| - Tested for carry-over effects
|
?
|
| - Tested for sequence effects
|
?
|
Interpretation of results
| Effect sizes reported (clinical vs. statistical significance)
|
?
|
| Side effects systematically recorded
|
?
|
| Side effects considered in result interpretation
|
?
|
| Ethics votum
|
?
|
Additional Notes
Additional Notes
