Therapeutic Drug Monitoring-Guided Antifungal Therapy Under Tyrosine Kinase Inhibitor Treatment in an Advanced Osteosarcoma Patient with Invasive Pulmonary Aspergillosis

Antifungal therapy for invasive pulmonary aspergillosis (IPA) can be challenging in cancer patients due to interpatient variability in pharmacokinetic properties of antifungals and potential drug-drug interactions (DDIs). This case report describes a 14-year-old boy with advanced osteosarcoma diagnosed with invasive pulmonary aspergillosis (IPA) after chemotherapy. Initial treatment of voriconazole showed poor improvement, as therapeutic drug monitoring (TDM) revealed exceptionally low trough concentration (0.28 μg/mL) even after dose increase. When voriconazole was switched to isavuconazole, favorable antifungal response was observed with isavuconazole trough concentrations ranging from 2.43 μg/mL to 4.12 μg/mL. Moreover, TDM also detected no obvious pharmacokinetic DDI between isavuconazole and apatinib but potential DDI between voriconazole and anlotinib in this patient. This case highlights the importance of individualized pharmacokinetic considerations in antifungal therapy in cancer patients. TDM may be a useful aid for therapeutic regimen decision and optimization.