Hortobagyi 1989.
| Study characteristics | ||
| Methods | Method of randomisation not clear (stratified according to performance status, number of organ sites involved by metastases, cumulative dose of prior anthracyclines, and whether prior anthracycline therapy had been given as postoperative adjuvant or as palliative treatment for metastatic disease) | |
| Participants | 52 women (aged 28 to 74 years) with progressive metastatic breast cancer treated with epirubicin. Prior anthracycline therapy in 21 women in the continuous infusion group and 12 women in the bolus infusion group; for 2 women in the bolus infusion group it was unclear; cumulative dose of prior anthracycline therapy nm. Prior cardiac radiotherapy nm; prior cardiac dysfunction possible (number of participants nm) | |
| Interventions | Epirubicin (peak dose 90 mg/m2) with either bolus (15 minutes) infusion (N = 25; median cumulative anthracycline dose including previous therapy 540 mg/m2; range 90 to 1055 mg/m2) or continuous (48 hours) infusion (N = 27; median cumulative anthracycline dose including previous therapy 630 mg/m2; range 110 to 1420 mg/m2) | |
| Outcomes | Heart failure (i.e. clinical heart failure defined as congestive heart failure; subclinical heart failure defined as a 15% or more decrease in LVEF as measured by cardiac scan or echocardiography). Tumour response (i.e. CR defined as disappearance of all clinical evidence of active tumour including symptoms and signs for a minimum of 4 weeks; PR defined as a greater than 50% decrease in the sum of the products of the longest perpendicular diameters of measurable lesions for at least 4 weeks. Simultaneous increase in the size of any lesion or the appearance of any new lesions was not permitted). Survival (OS was defined as survival from the initiation of present drug therapy). |
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| Notes | Length of follow‐up nm. The study was supported in part by a grant‐in‐aid from Farmitalia, but no information on the influence of funders was provided. |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | It was stated that this was a randomised study, but no further information on the methods of randomisation was provided |
| Allocation concealment (selection bias) | Unclear risk | It was stated that this was a randomised study, but no further information on the methods of randomisation was provided |
| Blinding of participants and personnel (performance bias) | Unclear risk | No information on blinding of participants and personnel was provided, although, due to the nature of the interventions, this was most likely not the case |
| Blinding of outcome assessment (detection bias): clinical heart failure | Unclear risk | No information on blinding of outcome assessors was provided for clinical heart failure |
| Blinding of outcome assessment (detection bias): subclinical heart failure (dichotomous and/or continuous) | Unclear risk | No information on blinding of outcome assessors was provided for subclinical heart failure |
| Blinding of outcome assessment (detection bias): tumour response | Unclear risk | No information on blinding of outcome assessors was provided for tumour response |
| Blinding of outcome assessment (detection bias): overall survival | Low risk | No information on blinding of outcome assessors was provided, but since this is not applicable for overall survival we judged this as a low risk of bias |
| Incomplete outcome data (attrition bias): clinical heart failure | Low risk | Almost all participants (96.2%) were included in the analysis |
| Incomplete outcome data (attrition bias): subclinical heart failure (dichotomous and/or continuous) | Low risk | Almost all participants (96.2%) were included in the analysis |
| Incomplete outcome data (attrition bias): tumour response | Low risk | Almost all participants (96.2%) were included in the analysis |
| Incomplete outcome data (attrition bias): overall survival | Low risk | Almost all participants (96.2%) were included in the analysis |
| Selective reporting (reporting bias) | Low risk | There was no reference to a protocol provided in the manuscript (and we did not search for it), but all expected outcomes were reported |
| Other bias | High risk |
Baseline imbalance between treatment arms related to outcome (prior cardiotoxic treatment, age, sex, and/or prior cardiac dysfunction): high (prior anthracycline use was not balanced between treatment arms; unclear if prior cardiac radiotherapy and prior cardiac dysfunction were balanced between treatment groups; all other items were balanced between treatment groups) Difference in length of follow‐up between treatment arms: no |