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Table 1 Heart failure and Cardiac Dysfunction incidence in contemporary trials with high cumulative doses of Doxorubicin

From: Dexrazoxane makes doxorubicin-induced heart failure a rare event in sarcoma patients receiving high cumulative doses

Trial

Population

Dexrazoxane Use (% use)

Cumulative Doxorubicin Dose (mg/m²)

Number of Patients

Age Range (years)

Heart Failure Incidence**

LVEF Decline ¶ (%)

LMS 04 Pautier et al. 2024 [22]

Leiomyosarcoma

No

360–450‡

149

30–86

5.4

NA

ANNOUNCE (< 450 mg/m²)

Jones et al. 2021 [27]

Soft-Tissue Sarcoma

Yes (38.6%)

< 450

153

NA*

2

16.2 (with dexrazoxane)

5.9 (without dexrazoxane)

ANNOUNCE (450–599 mg²)

Soft-Tissue Sarcoma

Yes (88.5%)

450–599

159

NA*

3

9.9 (with dexrazoxane)

23.5 (without dexrazoxane)

ANNOUNCE (≥ 600 mg²)

Soft-Tissue Sarcoma

Yes (90%)

≥ 600

89

NA*

1.1

12.5 (with dexrazoxane)

44.4 ( without dexrazoxane)

P 9754 Schwartz et al. 2016 [29]

Pediatric Osteosarcoma

Yes (100%)

450–600

242

3–30

0

2.1†

  1. ¶ LVEF (left ventricular ejection fraction) decline: LVEF decreased at least 10% and to < 50%
  2. *The median age for ANNOUNCE trial is 57 years, with a range of 29–82. No age information is available for each dose range
  3. ** For ANNOUNCE trial, CTCAE 4.0 grade 3 and 4 cardiac dysfunctions were considered heart failure in this context
  4. †Refers to CTCAE 4.0 Grade 1 or 2 cardiac dysfunction
  5. ‡LMS 04: 76% of patients received a cumulative doxorubicin dose of 360–450 mg/m²