Analyze pharmacokinetics of doxorubicin in children with cancer. Furthermore investigate the predictive role of troponin and natriuretic peptides for anthracycline-induced cardiotoxicity .

• Paediatric patients up to the age of 17 years will be included. Number and time points of PK sampling will depend on age and tumour type.
• PK samples will be collected from two doxorubicin administrations. Analyzing samples from two doxorubicin administrations will allow distinguishing between interindividual, intraindividual and residual variability.
• Doxorubicin and its major metabolite doxorubicinol will be measured in plasma using HPLC
• In addition, the natriuretic peptide BNP and the precursors NT-pro ANP and NT-proBNP as well as troponin T will be measured in plasma up to 28 days after doxorubicin administration to evaluate their use as clinical markers for cardiotoxicity.
• A data set of max 5 samples (3 +2 (in the 1st + 2nd Doxorubicin sampling periods)) will be collected in the younger children (< 3 years) and a data set of max. 8 samples ( 5 + 3) will be collected in the older children. Samples will be taken at predefined time points/ time intervals.
• An additional DNA sample will be taken and analyzed for genetic polymorphisms. The influence of genotype on pharmacokinetics and metabolism will be investigated by appropriate statistical methods, including population pharmacokinetic analyses. Genes to study would include MDR1 and SLC22A16, both involved in the transport of doxorubicin and AKR1A1 and CBR1, both involved in the reduction of doxorubicin to doxorubicinol. Selected genotypes will be incorporated as covariates into the population pharmacokinetic models developed. The potential impact of genetic variation will be evaluated in the context of other sources of variability such as age, weight, gender etc

Inclusion Criteria:

• patients ≤ 17 years of age
• plan to receive at least two cycles of doxorubicin
• must be enrolled in a national or European protocol for treatment of Wilms Tumours, Neuroblastoma, Soft tissue sarcoma, Ewing Sarcoma or Acute lymphoblastic leukaemia and must be treated with doxorubicin according to that protocol Or Patients < 3 years enrolled or listed in any national or European study protocol for any paediatric malignancy. Treatment with doxorubicin has to be according to that protocol.
• Parents or legal representative(s) must provide written informed consent to participate in the trial according to national regulations. Patients that are able to understand should provide assent to participate in the trial.
• Life expectancy of at least 3 month
• Karnofsky performance status of ≥ 70%
• Additional blood withdrawal is acceptable for the patient. The decision is left to the investigator

Exclusion Criteria:

• prior cardiac problems