Different anthracycline derivates for reducing cardiotoxicity in cancer patients.
BACKGROUND
The use of anthracyclines is limited by the occurrence of cardiotoxicity. In an effort to prevent this cardiotoxicity, different anthracycline derivates have been studied.


OBJECTIVE
To determine the occurrence of cardiotoxicity with the use of different anthracycline derivates in cancer patients.


METHODS
We searched The Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library, Issue 2, 2009), MEDLINE (1966 to 29 May 2009) and EMBASE (1980 to 2 June 2009). In addition, we searched reference lists of relevant articles, conference proceedings and ongoing-trials-databases.


METHODS
Randomised controlled trials (RCTs) in which different anthracycline derivates were compared in cancer patients (children and adults).


METHODS
Two authors independently performed study selection, assessment of risk of bias and data-extraction including adverse effects.


RESULTS
We identified five RCTs of varying quality addressing epirubicin versus doxorubicin (1036 patients) with the same dose. The meta-analysis showed no evidence for a significant difference in the occurrence of clinical heart failure between the treatment groups (RR = 0.36, 95% CI 0.12 to 1.11). However, there is some suggestion of a lower rate of clinical heart failure in patients treated with epirubicin.We identified two RCTs with varying quality addressing liposomal-encapsulated doxorubicin versus conventional doxorubicin (521 patients). The meta-analysis showed a significantly lower rate of both clinical heart failure and clinical and subclinical heart failure combined in patients treated with liposomal-encapsulated doxorubicin (RR = 0.20, 95% CI 0.05 to 0.75 and RR = 0.38, 95% CI 0.24 to 0.59 respectively). It should be noted that in one of the studies patients in the liposomal-encapsulated doxorubicin group received a higher cumulative anthracycline dose than patients in the doxorubicin group.For the other possible combinations of different anthracycline derivates only one RCT (epirubicin versus liposomal-encapsulated doxorubicin) or no RCT was identified.


CONCLUSIONS
We are not able to favour either epirubicin or doxorubicin when given with the same dose. Based on the currently available evidence on heart failure, we conclude that in adults with a solid tumour liposomal-encapsulated doxorubicin should be favoured over doxorubicin. For both epirubicin versus doxorubicin and liposomal-encapsulated doxorubicin versus conventional doxorubicin no conclusions can be made about the effects of treatment in children treated with anthracyclines and also not in patients diagnosed with leukaemia. More research is needed. For other combinations of anthracycline derivates not enough evidence was available to make definitive conclusions about the occurrence of cardiotoxicity in patients treated with anthracyclines.
van Dalen
Elvira C
EC
Paediatric Oncology, Emma Children's Hospital / Academic Medical Center, PO Box 22660 (room F8-257), Amsterdam, Netherlands, 1100 DD.
Michiels
Erna Mc
EM
Caron
Huib N
HN
Kremer
Leontien Cm
LC
D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D002303:Cardiac Output, Low / Q000139:chemically induced; D002648:Child; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects*; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects*; D006321:Heart / Q000187:drug effects*; D006801:Humans; D008081:Liposomes; D009369:Neoplasms / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic
D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D015251:Epirubicin; D004317:Doxorubicin
Ann Oncol. 2002 Jun;13(6):819-29
12123328
Eur J Cancer Clin Oncol. 1987 Oct;23(10):1477-83
3479329
Leuk Lymphoma. 1995 Oct;19(3-4):329-35
8535227
Stat Med. 1998 Dec 30;17(24):2815-34
9921604
Clin Breast Cancer. 2004 Dec;5(5):358-63
15585073
Cancer Treat Rep. 1986 Feb;70(2):261-6
3456271
Cochrane Database Syst Rev. 2006 Oct 18;(4):CD005006
17054231
Gan To Kagaku Ryoho. 1989 Aug;16(8 Pt 2):3011-4
2782905
Haematologica. 1997 May-Jun;82(3):309-13
9234577
Cancer. 1981 Jan 1;47(1):207-14
7459811
Cancer. 1973 Aug;32(2):302-14
4353012
J Clin Pharmacol. 1996 Jan;36(1):55-63
8932544
Heart. 2002 Jul;88(1):81-2
12067953
Eur J Cancer. 2000 Mar;36(4):503-7
10717527
J Clin Oncol. 1985 Jun;3(6):818-26
3859587
Anticancer Res. 2003 Jan-Feb;23(1B):765-71
12680181
Anticancer Drugs. 2003 Mar;14(3):239-46
12634619
Int J Gynaecol Obstet. 1988 Oct;27(2):199-204
2903085
Br J Cancer. 2002 Jun 5;86(11):1697-700
12087452
Acta Oncol. 1988;27(1):75-6
2835069
Ann Intern Med. 1996 Jul 1;125(1):47-58
8644988
Eur J Cancer Clin Oncol. 1986 Nov;22(11):1379-85
3470179
Cancer Treat Rep. 1978 Jun;62(6):865-72
667860
Sarcoma. 2000;4(1-2):31-5
18521432
Leuk Lymphoma. 1993 Oct;11(3-4):275-9
8260898
Br J Haematol. 2008 Dec;143(5):681-9
18950458
Ann Oncol. 2004 Oct;15(10):1527-34
15367414
Eur J Cancer. 2006 Dec;42(18):3191-8
16987655
Semin Oncol. 2006 Feb;33(1):2-14
16473642
Haematologica. 1998 Sep;83(9):800-11
9825577
Onkologie. 1986 Aug;9 Suppl 1:8-10
3528969
Clin Oncol (R Coll Radiol). 1993;5(2):80-4
8481365
J Clin Oncol. 1988 Apr;6(4):679-88
2895801
J Cancer Res Clin Oncol. 2006 Jan;132(1):35-40
16205946
Gan To Kagaku Ryoho. 1984 Oct;11(10):2170-6
6593004
Paediatr Drugs. 2005;7(3):187-202
15977964
Eur J Cancer Clin Oncol. 1987 Sep;23(9):1379-84
3315698
JAMA. 1995 Feb 1;273(5):408-12
7823387
J Clin Oncol. 2001 Mar 1;19(5):1444-54
11230490
Haematologica. 1993 Sep-Oct;78(5):306-12
8314160
Eur J Cancer. 2001 Jun;37(9):1132-40
11378344
Lancet. 1969 Apr 19;1(7599):837
4180385
Leuk Lymphoma. 2005 Jul;46(7):1023-8
16019553
Cancer Treat Rep. 1978 Jun;62(6):935-9
667871
Clin Lymphoma Myeloma. 2005 Sep;6(2):122-30
16231850
Eur J Haematol. 1991 May;46(5):301-5
2044726
Am J Clin Oncol. 1992 Apr;15(2):129-34
1553900
Cancer. 1998 Jun 1;82(11):2282-8
9610711
Med Oncol Tumor Pharmacother. 1989;6(2):163-9
2473364
Clin Cardiol. 1998 Sep;21(9):665-70
9755384
Med Pediatr Oncol. 1986;14(1):26-9
3512971
Br J Haematol. 2005 Aug;130(4):536-41
16098067
Cancer. 2002 Jan 1;94(1):25-36
11815957
Int J Cardiol. 2008 Aug 29;128(3):316-25
17707098
Am J Hematol. 2002 Dec;71(4):241-7
12447951
Am J Clin Oncol. 1991 Feb;14(1):38-44
1987737
Oncology. 1989;46(1):1-5
2915887
J Clin Oncol. 2001 May 15;19(10):2705-13
11352963
J Clin Oncol. 2005 Apr 20;23(12):2873; author reply 2873-4
15838014
Neoplasma. 1973;20(1):87-96
4573873
Eur J Cancer. 1991;27(6):750-5
1829918
Leukemia. 2001 Mar;15(3):348-54
11237056
Ann Oncol. 2002 Apr;13(4):503-12
12056699
Br J Cancer. 1998 Jun;77(12):2257-63
9649142
Blood. 1982 Aug;60(2):454-62
6953986
Ann Oncol. 2004 Mar;15(3):440-9
14998846
Br J Cancer. 1998 Dec;78(12):1634-9
9862576
Med Pediatr Oncol. 1995 Mar;24(3):171-5
7530801
Int J Cardiol. 2009 Jun 12;135(1):72-7
18572266
Am J Clin Oncol. 1989 Feb;12(1):57-62
2643296
Crit Rev Oncol Hematol. 1991;11(1):43-64
1831987
Klin Padiatr. 1988 May-Jun;200(3):190-9
3062255
Semin Oncol. 1995 Feb;22(1 Suppl 2):18-22
7846537
Cancer. 2006 Feb 15;106(4):848-58
16404741
Klin Padiatr. 2001 Jul-Aug;213(4):175-85
11528551
Int J Clin Pharmacol Ther Toxicol. 1989 May;27(5):217-21
2737789
J Clin Oncol. 1988 Jun;6(6):976-82
2897433
J Clin Oncol. 1991 Dec;9(12):2148-52
1960557
Onkologie. 1990 Feb;13(1):24-7
2186320
Gan To Kagaku Ryoho. 1983 Nov;10(11):2393-8
6639100