Applying Pharmacogenomics Can Help Reduce Toxicity in Pediatric Oncology

(Pharmacy Practice News) – Because pharmacogenetic factors influence the effects of pediatric oncologic therapies, genetic information is increasingly being used to help minimize toxicities in pediatric patients with cancer, but some experts urge a cautious approach.

“The goal is to identify markers of clinical, diagnostic utility that will prevent severe, adverse events in children,” said Shahrad Rod Rassekh, MD, MHSc, a pediatric oncologist and a clinical assistant professor at British Columbia Children’s Hospital, in Vancouver, British Columbia.

During a presentation at the 2014 Congress of the International Society of Pediatric Oncology, Dr. Rassekh said that factors such as a child’s size, diet and the presence of concomitant diseases influence how a drug is dosed, and genetic information is yet another factor to consider when making any dose adjustments in pediatric oncology.

Dr. Rassekh gave the example of the gene coding for thiopurine S-methyltransferase (TPMT) and its relationship to the treatment of acute lymphoblastic leukemia (ALL) with 6-mercaptopurine. The vast majority of patients with ALL are cured, but about 10% do not achieve a cure, he said. Research suggests that TPMT genotype affects the efficacy of ALL treatment. One study found that patients who were heterozygous for allelic variants of TPMT that conferred reduced enzyme activity had a significantly reduced rate of minimal residual disease positivity compared with patients who carried homozygous wild-type alleles (JAMA 2005;293[12]:1485-1489, PMID: 15784872).

In another example, Dr. Rassekh and his co-investigators have validated genetic variants in two genes that are predictive of anthracycline-induced cardiotoxicity. They have put forth a prediction model, taking into account clinical risk factors, to detect patients who are at low versus high risk for developing cardiotoxicity (Pediatr Blood Cancer 2013;60[8]:1375-1381, PMID: 23441093).

 

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