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Two patients undergo chemotherapy for osteosarcoma of the right proximal tibia. The patients are the same age, were diagnosed within two years of one another, and received identical chemotherapy regimens consisting of cisplatin, doxorubicin and methotrexate. Treatment was successful – both patients are alive and well. However, after only two cycles of chemotherapy, one patient developed bilateral hearing loss with a progressive decline in audiological function, while the other patient’s hearing remained unimpaired. Ototoxicity is a well-characterized adverse drug reaction (ADR) to cisplatin, but why two patients who are so alike can experience profoundly different outcomes is perplexing. Heterogeneity of drug response is a common issue encountered in clinical practice.

Using pharmacogenetics to understand adverse drug reactions in children