PMID- 10531570
OWN - NLM
STAT- MEDLINE
DCOM- 19991123
LR  - 20220311
IS  - 0098-1532 (Print)
IS  - 0098-1532 (Linking)
VI  - 33
IP  - 5
DP  - 1999 Nov
TI  - Hepatotoxicity in patients treated according to the nephroblastoma trial and 
      study SIOP-9/GPOH.
PG  - 462-9
AB  - BACKGROUND: A major problem for children receiving Wilms tumor (WT) chemotherapy 
      is hepatotoxicity, which may even be life-threatening. Dactinomycin (AMD) has 
      been shown to be an important factor, as has abdominal irradiation. PROCEDURE: In 
      the nephroblastoma trial and study SIOP-9 (SIOP-9) two different regimens for the 
      application of AMD were used (standard dose over 3-5 days vs. double dose on a 
      single day). In children at increased risk for local relapse, postoperative 
      abdominal irradiation was given. We analyzed the influence of AMD and 
      radiotherapy on the development of hepatotoxicity in 481 children treated in 
      centers of the German Paediatric Oncology and Haematology Society (GPOH). A 
      special questionaire was sent out for all patients with reduced treatment or 
      delay of more than 1 week because of hepatotoxicity. Because SIOP and the 
      National Wilms Tumor Study (NWTS) used different criteria to asses 
      hepatotoxicity,we applied both definitions. RESULTS: All 72 cases of mild or 
      severe hepatotoxicity occurred during treatment with AMD over 3-5 days with the 
      standard dose (9.4-22.5 microgram/kg/week) compared to none in the group 
      receiving a double dose on 1 day (3.75-8 microgram/kg/week; P < 0.001). 
      Irradiation of the right abdomen, including parts of the liver, enhanced liver 
      toxicity significantly, with a relative risk (RR) of 2.6 (P < 0.003). 
      Preoperative liver toxicity was more frequent in smaller children (P = 0.02) and 
      especially if no dose reduction was done in children with body weight of less 
      than 12 kg (RR 5.3, P = 0.01). If severe liver toxicity was defined according to 
      NWTS criteria, 10% of all treated patients were affected compared to 4.8% if 
      McDonald's criteria for hepatic veno-occlusive disease (VOD) were applied. 
      CONCLUSIONS: To diminish the hepatotoxicity of WT treatment, AMD dose intensity 
      should be reduced (below 10 microgram/kg per week), especially in smaller 
      children or when the liver is irradiated.
CI  - Copyright 1999 Wiley-Liss, Inc.
FAU - Ludwig, R
AU  - Ludwig R
AD  - Children's Hospital, University of Heidelberg, Heidelberg, Germany. 
      r.ludwig@circular.de
FAU - Weirich, A
AU  - Weirich A
FAU - Abel, U
AU  - Abel U
FAU - Hofmann, W
AU  - Hofmann W
FAU - Graf, N
AU  - Graf N
FAU - Tournade, M F
AU  - Tournade MF
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Med Pediatr Oncol
JT  - Medical and pediatric oncology
JID - 7506654
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 1CC1JFE158 (Dactinomycin)
SB  - IM
MH  - Adolescent
MH  - Antibiotics, Antineoplastic/administration & dosage/*adverse effects
MH  - Child
MH  - Child, Preschool
MH  - Dactinomycin/administration & dosage/*adverse effects
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Infant
MH  - Kidney Neoplasms/*drug therapy/radiotherapy
MH  - Liver/*drug effects
MH  - Male
MH  - Wilms Tumor/*drug therapy/radiotherapy
EDAT- 1999/10/26 00:00
MHDA- 1999/10/26 00:01
CRDT- 1999/10/26 00:00
PHST- 1999/10/26 00:00 [pubmed]
PHST- 1999/10/26 00:01 [medline]
PHST- 1999/10/26 00:00 [entrez]
AID - 10.1002/(SICI)1096-911X(199911)33:5<462::AID-MPO5>3.0.CO;2-8 [pii]
AID - 10.1002/(sici)1096-911x(199911)33:5<462::aid-mpo5>3.0.co;2-8 [doi]
PST - ppublish
SO  - Med Pediatr Oncol. 1999 Nov;33(5):462-9. doi: 
      10.1002/(sici)1096-911x(199911)33:5<462::aid-mpo5>3.0.co;2-8.