Swain 1997a(088006).

Methods	Block randomisation according to a prospectively prepared randomisation list (a separate list was prepared for each investigational site and within each site, the assignments were stratified relative to the presence or absence of cardiac risk factors and on the basis of measurable versus nonmeasurable disease).
Participants	185 patients (aged 23‐79 years; all females) with breast cancer (stage IIIB or IV) treated with doxorubicin (cumulative dose <100‐1750 mg/m2; peak dose (i.e. maximal dose received in 1 week) 50 mg/m2; infusion duration nm), fluorouracil and cyclophosphamide. No prior anthracycline therapy. Prior cardiac radiotherapy in 3 patients in the dexrazoxane group and 9 patients in the control group (dose nm). No prior cardiac dysfunction.
Interventions	Dexrazoxane (10:1 ratio of study drug to doxorubicin; slow IV push or rapid‐drip IV infusion between 15 and 30 minutes before doxorubicin) (n=81) versus placebo (n=104).
Outcomes	Heart failure (i.e. clinical heart failure defined as 2 or more of the following: cardiomegaly established by radiography, basilar rales, S3 gallop or paroxysmal nocturnal dyspnoea, orthopnoea, or significant dyspnoea on exertion; subclinical heart failure defined as 1) decline in LVEF as measured by MUGA from baseline of ≥10% below the institution's LLN, 2) a decline in LVEF as measured by MUGA of at least 20% from baseline or 3) decline in LVEF as measured by MUGA to at least 5% below the institution's LLN). Response rate (according to ECOG criteria; see notes). Survival. Adverse effects (according to ECOG criteria).
Notes	Length of follow up: in the intervention group 397 days (6‐1393); in the control group 517 days (range 29‐1429). Median age in intervention group: 56 years; median age in control group: 59.5 years. Cumulative anthracycline dose in intervention and control group nm.