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Which chemotherapy drugs have the highest cardiotoxicity risk in pediatric cancer?

A recent study published in JAMA Oncology analyzed data generated from over 28,000 childhood cancer survivors and compared the lifetime cardiotoxicity risk in different chemotherapeutic drugs used for treatment.

 

One out of every five Canadian kids who are diagnosed with childhood cancer will not survive. Childhood or pediatric cancer can affect any organ and in Canada is one of the leading cause of childhood mortality. Chemotherapy drugs are frontline therapies used to treat pediatric cancers. Even though chemotherapy treatment can increase survival, it usually comes with a heavy price.

Almost 30,000 childhood cancer survivors living in Canada battle many toxic, long-term and undesirable side effects. Almost 75% of childhood cancer develop one or more chronic conditions that significantly reduces the overall quality of life. For this reason, there is an impetus to devise less harsh chemotherapy regimens and accurately evaluate the extent of chronic side effects that are caused by these drugs.

Anthracyclines are the mainstay of chemotherapy regimens for pediatric cancers

Anthracyclines such as doxorubicin, danorubicin, epirubicin and mitoxantrone form the mainstay of chemotherapy regimens used to treat pediatric cancers. However, an accurate estimate of their overall toxicity is debatable. Most of these drugs cause cardiotoxicity to varying extent – a condition which can lead to abnormalities in heart muscle and compromise heart function.

Given that these drugs can cause a range of other toxic side effects, and are often used at different doses for treating many different pediatric cancer subtypes, it is very difficult to compare and estimate the overall life-time risk of cardiotoxicity from these drugs.

U.S.-based investigators from Fred Hutchinson Cancer Research Center in Seattle, St. Jude Children’s Research Hospital in Memphis, the Duke University School of Medicine in Raleigh-Durham, and the University of Washington, Seattle and various other investigators from Netherland teamed up to conduct a study aimed at evaluating the overall cardiotoxicity risk of different anthracycline chemotherapy drugs. They published their results in JAMA Oncology.

Mitoxantron had higher overall cardiotoxicity

The investigators pooled data from over 28,000 childhood cancer survivors that have battled leukemia, lymphomas, brain tumors, neuroblastoma, kidney tumors, bone tumors, soft tissue sarcomas, and other forms of malignancies. The study revealed that in comparison to doxorubicin, danorubicin was associated with a lower risk of cardiotoxicity. In contrast Mitoxantron had a higher overall cardiotoxicity in comparison to doxorubicin. The toxicity of epirubicin was comparable to doxorubicin. The authors suggested that it is important to consider long-term cardiotoxicity risk of chemotherapy drugs when designing drug-regimens for treatment of pediatric cancers to improve the overall long term quality of life for survivors.

Written by Vinayak Khattar, Ph.D., M.B.A

References:

  1. Feijen, E. A. M., Leisenring, W. M., Stratton, K. L., Ness, K. K., van der Pal, H. J. H., van Dalen, E. C., . . . Chow, E. J. (2019). Derivation of Anthracycline and Anthraquinone Equivalence Ratios to Doxorubicin for Late-Onset Cardiotoxicity. JAMA Oncol. doi:10.1001/jamaoncol.2018.6634
  2. https://www.kidscancercare.ab.ca/childhood-cancer/stats
  3. https://www.eurekalert.org/pub_releases/2019-01/uoth-dac013119.php
Vinayak Khattar PhD MBA
Vinayak Khattar PhD MBA
Vinayak Khattar completed his Master of Biotechnology at D.Y. Patil University in India. He received his Ph.D. in Cancer Biology at the University of Alabama at Birmingham (UAB) and then completed his M.B.A from the UAB Collat School of Business. His research interests lie in identifying mechanisms that dictate protein stability in cancer cells, immuno-oncology, and bone biology. He has seven peer-reviewed publications, over 40 citations, and three awards. He likes to watch Netflix documentaries with his family during his free time.
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