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 different types of childhood cancer should be based on the available evidence on 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 2006, issue 4), MEDLINE (1966 to January 2007) and EMBASE (1980 to January 2007). 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, quality assessment and data-extraction.


RESULTS
We identified RCTs for 5 types of tumour: acute lymphoblastic leukaemia (ALL) (n=3; 912 children), Wilms' tumour (n=1; 316 children), rhabdomyosarcoma/undifferentiated sarcoma (n=1; 413 children), Ewing's sarcoma (n=1; 94 children), and non-Hodgkin lymphoma (n=1; 284 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 survival in favour of treatment with anthracyclines was identified. The hazard ratios for overall and event-free survival in Wilms' tumour were 1.85 (95% CI 1.09 to 3.15) and 2.21 (95% CI 1.44 to 3.40), respectively. For patients with Ewing's sarcoma only descriptive results were available (P = 0.02 for overall survival and P = 0.01 for event-free survival). For both rhabdomyosarcoma/undifferentiated sarcoma and non-Hodgkin lymphoma no difference in antitumour efficacy between the treatment groups was identified. Clinical cardiotoxicity was evaluated in 3 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, it should be noted that "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, and non-Hodgkin lymphoma only 1 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. More high quality research is needed.
van Dalen
Elvira C
EC
Paediatric Oncology, Emma Children's Hospital / Academic Medical Center, PO Box 22660 (room F8-257), Amsterdam, Netherlands, 1100 DD. e.c.vandalen@amc.uva.nl
Raphaël
Martine F
MF
Caron
Huib N
HN
Kremer
Leontien Cm
LC
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; D006331:Heart Diseases / Q000139:chemically induced; D006801:Humans; D007680:Kidney 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