HHE Sponsored handbook: Cardioprotection in clinical | Page 5

HHE 2019 5
Cardioprotection in children/adolescents
Adding dexrazoxane to doxorubicin significantly
reduced cardiac outcome measures compared
with doxorubicin alone in children/adolescents
with T-cell acute lymphoblastic leukaemia or
lymphoblastic-non-Hodgkin lymphoma 3 years
after doxorubicin treatment (Figure 1C). 17
FIGURE 1C
Cardioprotective effects of
dexrazoxane in † children/adolescents
p=0.053
† p=0.005
0.37
0.34
receiving
doxorubicin
for treatment
1.00
(n=158) (n=149)
† p=0.053
† p=0.005
of ALL/NHL
-0.05
0.37
0.34
Cardioxane® mode of action
Anthracycline-induced cardiotoxicity is a
multifactorial process involving direct reaction
with ferric ions (Fe3+), leading to the formation
of free radicals that disrupt cellular constituents,
causing cellular dysfunction and cell death. 18,19
Cardioxane ® binds ferric ions, preventing the
formation of complexes with anthracyclines. 20
By chelating ferric ions, Cardioxane ® abrogates
anthracycline-induced damage in mitochondrial
function, preventing the impaired cardiac
function (Figure 2). 21
0.50
1.00
LV
-0.50
0.00
(n=158)
0.00
0.50
fractional
1.00
-1.00
-0.50
shortening
0.37
(n=158)
0.34
(n=149)
0.50
-1.50
-1.00
-1.68
(n=61)
-0.05 Normal
(n=83)
-0.77
(n=84)
Baseline End of DOX
treatment
(‡p=0.42)
(‡n=38 v n=51) 3 years
(‡p=0.43)
(‡n=55 v n=56)
† p=0.007 † p=0.346 † p=0.014
0.80 (n=156)
† p=0.007 † p=0.346 † p=0.014
0.80
0.40 0.32
(n=156)
Baseline
Baseline
(‡p=0.42)
(‡n=38 v n=51)
-2.00
-2.50
LV wall thickness
0.32
-0.05
(n=83)
-0.77
† p=0.005
(n=84)
Normal
3 years
Normal
(‡p=0.43)
(‡n=55
v
n=56)
3 years
-1.50
† p=0.053 -0.90
-1.68
(n=82)
(n=61)
-0.77
(n=84)
-1.68
End of DOX
(n=61)
treatment
(‡p=0.42)
End of DOX
(‡n=38 v n=51)
treatment
-1.00
-2.50
Safety profile of Cardioxane ®
The most common adverse reactions are
haematological and gastroenterological, primarily
anaemia, leukopenia, nausea, vomiting and
stomatitis, as well as asthenia and alopecia nail
disorders. Overall, studies show that Cardioxane ®
might lead to a slight increase in the incidence
of haematological toxicities, although the routine
administration of chemotherapy treatment is not
impacted. 12,16
Myelosuppressive effects of Cardioxane ®
may be additive to those of chemotherapy.
Haematological monitoring is necessary.
Cardioxane ® is administered together with
anthracycline chemotherapy and, consequently,
the relative contributions of anthracycline and >
-0.90
(n=82)
-0.90
(n=82)
0.00
-2.00
-1.50
-0.50
-2.50
-2.00
(n=83)
(n=149)
0.40
0.00
0.80
0.00
-0.40
† p=0.007 -0.16
(n=145)
0.32
(n=156)
0.40
-0.40
-0.80
0.00
-0.80
-1.20
-0.40
-1.20
-0.16
(n=145)
-0.16
(n=145)
Baseline
Baseline
-0.35
(n=81)
-0.55
† p=0.346
(n=60)
-0.35
(n=81)
-0.55
(n=60)
-0.35
(n=81)
-0.55
(n=60)
End of DOX
treatment
(‡p=0.013)
End of DOX
(‡n=38
v n=49)
treatment
(‡p=0.43)
(‡n=55 v n=56)
-0.13
(n=79)
-0.13 Normal
† p=0.014 (n=79)
-0.69
(n=79)
Normal
-0.69
(n=79)
-0.13
(n=79)
Normal
-0.69
3 years
(n=79)
(‡p=0.206)
3 years
(‡p=0.206)
(‡p=0.013)
(‡n=38 v n=49)
-0.80
-1.20
Before treatment After treatment P-value
102 ± 8.8 105 ± 7.2 NS
12.7 ± 2.2 13.7 ± 7.8 NS
78.6 ± 6.3 83.1 ± 7.6 NS
64.1 ± 6.3 59.6 ± 4.7 NS
5.0 ± 1.4 3.1 ± 1.3 <0.05
Epirubicin plus dexrazoxane (n=61)
Baseline
End of ratio
DOX (LV remodelling)
3 years
LV thickness-to-dimension
0.40
0.40
0.00
0.00
-0.40
0.40
-0.40
-0.80
0.00
-0.80
-1.20
-0.40
-1.20
0.16
(n=157)
0.16
(n=157)
0.16
(n=157)
-0.11
(n=145)
-0.11
(n=145)
-0.11
(n=145)
Baseline
Baseline
-0.80
treatment
† p=0.091
(‡p=0.013)
(‡n=38 v n=49)
† p=0.091
(‡p=0.206)
† p=0.006
† p=0.006
-0.09
(n=82)
-0.38
(n=82)
-0.73
† p=0.091
(n=61)
-0.38
(n=82)
-0.73
(n=61)
-0.38
(n=82)
-0.73
(n=61)
End of DOX
treatment
(‡p=0.039)
End of DOX
(‡n=38
v n=50)
treatment
-0.09
Normal
(n=82)
† p=0.006
Normal
-0.75
(n=83)
-0.09
-0.75
(n=82)
(n=83)
Normal
3 years
-0.75
(‡p=0.217)
(n=83)
3 years
(‡p=0.217)
(‡p=0.039)
(‡n=38 v n=50)
† Comparison between groups
‡ Comparison of change in mean z score
End of
DOX groups 3 years
between
treatment
(‡p=0.217)
(‡p=0.039)
ALL, acute lymphoblastic leukaemia;
DOX, doxorubicin; LV, left ventrcular;
(‡n=38
v
n=50)
NHL, non-Hodgkin lymphoma
Doxorubicin only
Dexrazoxane
+ Doxorubicin
-1.20
Baseline