Life-Threatening Irinotecan-Induced Toxicity inan Adult Patient with Alveolar Rhabdomyosarcoma:The Role of a UGT1A1 Polymorphism

Alveolar rhabdomyosarcoma (AR) in adult patients is an exceptional malignancy. Management of AR is based on (neo)adjuvantchemotherapy combining ifosfamide, vincristine, and actinomycin D and local curative-intent surgery/radiotherapy. In cases ofrelapsing AR, the combination of temozolomide/irinotecan is regarded as a possible option. Here we describe life-threatening long-lasting toxicity related to the 1st cycle of irinotecan-based chemotherapy in a 56-year-old woman suffering from locally advancedand metastatic head and neck AR. The patient experienced grade 4 vomiting and diarrheas resulting in acute functional renalfailure, associated with grade 4 neutropenia complicated by severe septic shock. The hospital stay duration was 40 days. The analysisof the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene revealed homozygous UGT1A1∗28 polymorphism withan associated homozygous mutation c.-3275T>G; the latter is associated with a decrease of about 80% of UGT1A1 transcriptionexplaining this irinotecan induced toxicity. Physician must be aware of the potential hematological (mainly neutropenia andinfectious disease) and digestive (mainly diarrhea) toxicities caused by irinotecan and especially when the patient presents aUGT1A1∗28 homozygous allele. UGT1A genotyping performed before initiating treatment is useful to anticipate severe toxicreaction to irinotecan and improve the benefit/risk ratio of its use