In pediatric cancer patients, mitoxantrone appears to be at least ten times as cardiotoxic as doxorubicin therapy, while daunorubicin therapy may be less so, according to a large cohort study.
"With 5-year survival of childhood cancer now reaching nearly 85%, balancing the potential long-term adverse effects of otherwise effective cancer treatments is an important consideration," researchers write in JAMA Oncology, online January 31.
In children, "a doxorubicin to mitoxantrone substitution rule of 4:1 has been commonly accepted for both anti-tumor efficacy and toxicity," add Dr. Eric J. Chow of Fred Hutchinson Cancer Research Center, in Seattle, and colleagues.
To provide more robust evidence, the team studied more than 28,000 childhood cancer survivors (median age at diagnosis, 6.1 years), including 9,330 treated with doxorubicin, 4,433 with daunorubicin, 342 with epirubicin, 241 with idarubicin, and 265 with mitoxantrone.
After adjusting for factors including chest radiotherapy and age at cancer diagnosis, the risk of severe, life-threatening or fatal cardiomyopathy by age 40 was evaluated via agent-specific Cox proportional hazards models.
After a median follow-up of 20 years, there were 399 cases of cardiomyopathy. Relative to doxorubicin, the agent-specific cardiomyopathy equivalence ratio was 0.6 for daunorubicin, 0.8 for epirubicin and 10.5 for mitoxantrone.
"In contrast to the commonly used 4:1 (mitoxantrone to doxorubicin) and 1:1 (daunorubicin to doxorubicin) ratios for late cardiomyopathy, the ratios we found were more like 10+:1 and about 0.5:1, respectively,” Dr. Chow told Reuters Health by email.
"These findings may impact the choice of anthracyclines/anthraquinones in future treatment protocols," he said.
In particular, he and his colleagues conclude, "our findings may . . . allow for better personalization when regimens with equivalent anticancer efficacy may be evaluated more accurately with respect to their long-term cardiotoxicity risk."
SOURCE: https://bit.ly/2Dxj1Up
JAMA Oncol 2019.
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