Heidenreich 2004.

Study characteristics
Methods	Method of randomisation not clear
Participants	48 men (aged 58 to 79 years) with metastatic hormone‐refractory prostate carcinoma treated with liposomal doxorubicin (Caelyx). No prior anthracycline therapy; prior cardiac radiotherapy nm; no prior cardiac dysfunction
Interventions	Liposomal doxorubicin (Caelyx; 1‐hour infusion) with a peak dose of either 25 mg/m2 (N = 22; cumulative anthracycline dose 323.5 mg per man; range 50 to 600 mg per man) or 50 mg/m2 (N = 26; cumulative anthracycline dose 416.13 mg per man; range 100 to 1200 mg per man)
Outcomes	Heart failure (i.e. clinical heart failure defined as congestive heart failure; subclinical heart failure defined as LVEF < 40% on echocardiography). Response rate (i.e. objective palliative response rate defined as a reduction in serum PSA levels by >= 50% relative to baseline, with this reduction persisting for >= 4 weeks and accompanied by stabilisation or improvement in the man's performance status). Quality of life (according to the 30‐item European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire). Adverse effects other than cardiac damage (according to the National Cancer Institute of Canada/CALGB grading system).
Notes	Mean length of follow‐up 42 months. Anthracycline doses were not available as mg/m2. Some of the information provided in this table was not included in the article, but was provided by the author upon our request. No funding documented.
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): adverse effects other than cardiac damage	Unclear risk	No information on blinding of outcome assessors was provided for adverse effects other than cardiac damage
Blinding of outcome assessment (detection bias): quality of life	Unclear risk	No information on blinding of outcome assessors was provided for quality of life
Incomplete outcome data (attrition bias): clinical heart failure	Low risk	All men were included in the analysis
Incomplete outcome data (attrition bias): subclinical heart failure (dichotomous and/or continuous)	Low risk	All men were included in the analysis
Incomplete outcome data (attrition bias): tumour response	Low risk	Almost all men (96%) were included in the analysis of clinical heart failure
Incomplete outcome data (attrition bias): adverse effects other than cardiac damage	Low risk	All men were included in the analysis
Incomplete outcome data (attrition bias): quality of life	Unclear risk	It was not documented in how many men quality of life was assessed
Selective reporting (reporting bias)	High risk	There was no reference to a protocol provided in the manuscript (and we did not search for it), but not all expected outcomes were reported in a useful manner
Other bias	Unclear risk	Baseline imbalance between treatment arms related to outcome (prior cardiotoxic treatment, age, sex, and/or prior cardiac dysfunction): unclear (unclear if prior cardiotoxic treatment was balanced between treatment groups; the other items were balanced between treatment groups) Difference in length of follow‐up between treatment arms: unclear (not reported)