Treatment including anthracyclines versus treatment not including anthracyclines for childhood cancer.
BACKGROUND
One of the most important adverse effects of anthracyclines is cardiotoxicity. A well-informed decision on the use of anthracyclines in the treatment of childhood cancers should be based on evidence regarding both antitumour efficacy and cardiotoxicity.


OBJECTIVE
To compare antitumour efficacy of treatment including or not including anthracyclines in children with childhood cancer.


METHODS
We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 2), MEDLINE (1966 to March 2010) and EMBASE (1980 to March 2010). In addition, we searched reference lists of relevant articles, conference proceedings and ongoing trials databases.


METHODS
Randomised controlled trials (RCTs) comparing treatment of any type of childhood cancer with and without anthracyclines and reporting outcomes concerning antitumour efficacy.


METHODS
Two reviewers independently performed the study selection, risk of bias assessment and data extraction.


RESULTS
We identified RCTs for six types of tumour: acute lymphoblastic leukaemia (ALL) (three trials; 912 children), Wilms' tumour (one trial; 316 children), rhabdomyosarcoma/undifferentiated sarcoma (one trial; 413 children), Ewing's sarcoma (one trial; 94 children), non-Hodgkin lymphoma (one trial; 284 children) and hepatoblastoma (one trial; 255 children). All studies had methodological limitations. For ALL no evidence of a significant difference in antitumour efficacy was identified in the meta-analyses, but in most individual studies there was a suggestion of better antitumour efficacy in patients treated with anthracyclines. For both Wilms' tumour and Ewing's sarcoma a significant difference in event-free and overall survival in favour of treatment with anthracyclines was identified, although for Wilms' tumour the significant difference in overall survival disappears with long-term follow-up. For rhabdomyosarcoma/undifferentiated sarcoma, non-Hodgkin lymphoma and hepatoblastoma no difference in antitumour efficacy between the treatment groups was identified. Clinical cardiotoxicity was evaluated in three RCTs: no significant difference between both treatment groups was identified, but in all individual studies there was a suggestion of a lower rate of clinical cardiotoxicity in patients who did not receive anthracyclines. None of the studies evaluated asymptomatic cardiac dysfunction. For other childhood cancers no RCTs were identified.


CONCLUSIONS
At the moment no evidence from RCTs is available which underscores the use of anthracyclines in ALL. However, "no evidence of effect", as identified in this review, is not the same as "evidence of no effect". For Wilms' tumour, rhabdomyosarcoma/undifferentiated sarcoma, Ewing's sarcoma, non-Hodgkin lymphoma and hepatoblastoma only one RCT was available and, therefore, no definitive conclusions can be made about the antitumour efficacy of treatment with or without anthracyclines in these tumours. For other childhood cancers no RCTs were identified and therefore, no conclusions can be made about the antitumour efficacy of treatment with or without anthracyclines in these tumours.
Paediatric Oncology, Emma Children's Hospital / Academic Medical Center, PO Box 22660 (room A3-273), Amsterdam, Netherlands, 1100 DD.
Elvira C
EC
van Dalen
Martine F
MF
Raphaël
Huib N
HN
Caron
Leontien Cm
LC
Kremer
D000293:Adolescent; D018943:Anthracyclines / Q000009:adverse effects / Q000627:therapeutic use*; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy; D002648:Child; D002675:Child, Preschool; D006331:Heart Diseases / Q000139:chemically induced; D018197:Hepatoblastoma / Q000188:drug therapy; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007680:Kidney Neoplasms / Q000188:drug therapy; D008113:Liver Neoplasms / Q000188:drug therapy; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic; D012509:Sarcoma / Q000188:drug therapy; D009396:Wilms Tumor / Q000188:drug therapy
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic