Summary of findings 2. Dexrazoxane versus no cardioprotective intervention for preventing or reducing cardiotoxicity in children with cancer receiving anthracyclines.
| Dexrazoxane compared with no cardioprotective intervention for preventing or reducing cardiotoxicity in children with cancer receiving anthracyclines | ||||||
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Patient or population: children with cancer receiving anthracyclines Settings: hospital Intervention: dexrazoxane Comparison: no cardioprotective intervention | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect (95% CI) | No of participants (studies) | Quality of the evidence (GRADE) | Comments | |
| Assumed risk | Corresponding risk | |||||
| No cardioprotective intervention | Dexrazoxane | |||||
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Clinical heart failure Available‐case analysis Follow‐up ranged between 0.01 and 15 years (nm for 1 study) |
5 per 1000a | 1 per 1000 (0 to 19) | RR 0.20 (0.01 to 4.19) | 885 (3 studies) | ⊕⊕⊝⊝ Lowb,c |
In 2 studies, none of the participants developed clinical heart failure; the relative effect for those studies was not estimable. The available‐case, best‐case and worst‐case analyses showed identical results, including the GRADE assessment. |
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Cardiomyopathy/heart failure primary cause of death Available‐case analysis Follow‐up ranged between 0 and 15.5 years |
‐ | ‐ | Not estimable (see comments) | 1008 (3 studies) | ⊕⊕⊝⊝ Lowc,d |
In all studies, none of the participants had cardiomyopathy/heart failure as the primary cause of death; the relative effect was not estimable. The available‐case, best‐case and worst‐case analyses were identical, including the GRADE assessment. |
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Clinical heart failure and subclinical myocardial dysfunction combined Defined as (1) evidence of clinical congestive heart failure, (2) a reduction in LVEF as measured by MUGA to < 45% or (3) a decrease in LVEF as measured by MUGA of > 20 percentage points from baseline. Available‐case analysis Follow‐up nm for randomised participants |
667 per 1000a | 220 per 1000 (87 to 567) | RR 0.33 (0.13 to 0.85) | 33 (1 study) | ⊕⊕⊝⊝ Lowe,f |
The available‐case, best‐case and worst‐case analyses showed identical results, including the GRADE assessment. Study participants were aged between 4 and 24 years, so not all paediatric patients (< 21 years). |
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Clinical heart failure and subclinical myocardial dysfunction combined Defined as clinical heart failure (no definition provided) or subclinical myocardial dysfunction defined as decreased LVFS; however, it was stated that toxicity was graded according to NCI CTCAEv2 criteria, grade 3 or higher but LVFS is not included in that definition. Best‐case analysis Follow‐up ranged between 0.01 and 15 years |
‐ | ‐ | Not estimable (see comments) | 537 (1 study) | ⊕⊝⊝⊝ Very lowg,h |
For this outcome definition, only one study was available in which one of the treatment groups experienced no events. Thus, we were not able to calculate a RR and we used Fischer's exact test instead (P = 0.12). Only a best‐case analysis could be performed due to an unclear number of participants lost to follow‐up. |
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Overall mortality (Reported as number of participants who died) Follow‐up ranged between 0 and 15.5 years |
130 per 1000i | 131 per 1000 (95 to 179) | HR 1.01 (0.72 to 1.42) |
1008 (3 studies) | ⊕⊕⊝⊝ Lowc,d |
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| Progression‐free survival | No studies evaluated this outcome | |||||
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Tumour response rate Defined as number of complete remissions (no definition of complete remission provided). Best‐case analysis Follow‐up median 2.7 years |
950 per 1000a | 960 per 1000 (903 to 1000) | RR 1.01 (0.95 to 1.07) | 206 (1 study) | ⊕⊝⊝⊝ Very lowh,j |
Due to the nature of this outcome (number of participants with a complete remission), a high event rate is favourable. Only a best‐case analysis could be performed due to an unclear number of participants lost to follow‐up. |
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Tumour response rate Defined as number of complete responses (i.e. disappearance of active Hodgkin lymphoma (gallium negative, ≥ 70% decrease in the sum of the products of the perpendicular diameters of measurable lesions, and negative bone marrow or bone scan if initially positive)). Available‐case analysis Follow‐up nm (median follow‐up for participants without an event was 5.2 years). |
939 per 1000a | 864 per 1000 (789 to 949) | RR 0.92 (0.84 to 1.01) | 200 (1 study) | ⊕⊕⊝⊝ Lowh,k |
Due to the nature of this outcome (number of participants with a complete response), a high event rate is favourable. The available‐case, best‐case and worst‐case analyses showed identical results, including the GRADE assessment. |
| Quality of life | No studies evaluated this outcome | |||||
| Adverse effects other than cardiac damage | ||||||
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Secondary malignant neoplasms Available‐case analysis Follow‐up ranged between 0.01 and 15 years (nm for 1 study) |
10 per 1000a | 31 per 1000 (11 to 83) | RR 3.08 (1.13 to 8.38) | 1015 (3 studies) | ⊕⊕⊝⊝ Lowc,l |
The available‐case and worst‐case analyses were identical; the best‐case analysis showed the same direction of effect, but the result was not different between treatment groups (RR 2.51 (0.96 to 6.53). GRADE assessments were comparable for all analyses. |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence High quality: further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: we are very uncertain about the estimate. | ||||||
CI: confidence interval CTCAEv2: Common Terminology Criteria for Adverse Events, version 2 e.g.: for example HR: hazard ratio LVEF: left ventricular ejection fraction LVFS: left ventricular fractional shortening MUGA: multigated acquisition scan NCI: National Cancer institute nm: not mentioned P: P value RR: risk ratio
aThe assumed risk is based on the overall prevalence in the control group(s) of the included study/ies. bUnclear risk of selection and detection bias in 2 (67%) studies, high risk of performance bias in all studies, high risk of attrition bias and selective reporting in 1 (33%) study, unclear risk of other bias in all studies (downgraded 1 level). cAs these were relatively small studies with a total number of events fewer than 300 (the threshold rule‐of‐thumb value stated in the GRADEpro handbook (GRADEpro handbook), we downgraded one level. dUnclear risk of selection and other bias in all studies, high risk of performance bias in all studies (downgraded 1 level). eUnclear risk of selection, detection and other bias, and high risk of performance and attrition bias (downgraded 2 levels). fWe did not downgrade for imprecision; it was a small study but the effect was large, the 95% CI is small and below no effect. gUnclear risk of selection, detection and other bias, high risk of performance and attrition bias (downgraded 2 levels). hAs this was a small study with a total number of events fewer than 300 (the threshold rule‐of‐thumb value stated in the GRADEpro handbook (GRADEpro handbook), we downgraded 1 level. iThe assumed risk is based on the number of participants who died in the control groups of the included studies. jUnclear risk of attrition and other bias, high risk of performance bias and selective reporting (downgraded 2 levels). kUnclear risk of selection, detection and other bias; high risk of performance bias (downgraded 1 level). lUnclear risk of selection, detection and other bias in all studies; high risk of performance bias in all studies (downgraded 1 level).