Why pediatrics oncologists are still administering doxorubicine over long infusions rather than bolus, despite the results of multiple studies that shows the non significant difference between both methods of administration in the cardiotoxicity outcome. I am asking the question putting in consideration the fact that long infusions of doxorubine subject the patient to more sever toxicities of doxorubine and higher risk of extravastion of this vesicant drug.
In survivors of childhood high-risk ALL, continuous-infusion doxorubicin, compared with bolus-infusion, provided no long-term cardioprotection or improvement in ALL event-free survival, hence provided no benefit over bolus-infusion.
Link;
Pediatrics. 2012 Dec; 130(6): 1003–1011.
doi: 10.1542/peds.2012-0727
PMCID: PMC3507254
Continuous Versus Bolus Infusion of Doxorubicin in Children With ALL: Long-term Cardiac Outcomes
www.ncbi.nlm.nih.gov/...
National Center for Biotechnology Information
by SE Lipshultz - 2012
Dr.graymer, clinical trials on adults have actually shown that long infusions indeed reduces the cardiotoxixity; however, as dr. Khaleque shared, the pediatric studies, unlike adult studies, have shown that they offered them no benifits. But till now, pediatric oncologists are still using chemotherapy protocols that administer doxorubicin over long infusions (48-6hrs), so why they still using these protocols despite the proves of no benefits to justify the accociated risks
Hi
Because children,s heart is more sensitive to antracyclines cardiotoxicity than adult.
age,drug administration include infusion time and female sex are effective in antracyclines cardiotoxicity. Therefore long time infusion decreases cardiotoxicity.
Dear dr.abdolkarim,
Thank you for reply. As as dr. Khaleque shared a study comparing the long term outcome, showed no significant difference between infusion and bolus adminstration of doxorubicin. Still long infusion subject the patient to other side effects, and subject the patient to a higher risk of extravasation of this vesicant drug. So, I was searching for another reason that might make oncologists stick to this long infusion despite its risk compared of no documented benefits in pediatrics ( there are documen benefits for adults; though some institutes still administering it as bolus)
Dear Dr Elkadi
The greatest majority of doxorubicin administrations are done as bolus administrations.
The one solid tumour where 24 hour infusions are utilized is in osteosarcoma. The reason for this is the inhibitory effect of doxorubicin in primary osteosarcoma cells appeared to correlate with slow cell growth rate and absence of chemotherapy-induced G2 cell cycle arrest.
Thus your answer lies in the replication rate of the tumour cells you want to treat. Osteosarcoma slow vs heamatological malignancies faster.
At mean of 7 years after end of therapy, diminished cardiac function was seen in 20% of the patient who had received bolus anthracycline compared to 11% of patients who had received it via infusion. This difference did not prove to be statistically significant. Med Pediatr Oncol 2003;40:343–347
Dear Dr. Jawass,
As mentioned in the above answers, long infusion did't provide significant benefits over bolus administration in pediatric population (unlike adults). The question is why pediatric oncologists are still administrating doxorubicin by long infusions, in protocols such as LMB, where the long infusion was only justified in the protocol to avoid cardiotoxicity, despite the other side effects and risks associated with long infusions
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