Gartrell J, Panetta JC, Baker SD, Chen YL, Hawkins DS, Ostrenga A, Scharschmidt TJ, Spunt SL, Wang D, Weiss AR. The effects of pazopanib on doxorubicin pharmacokinetics in children and adults with non-rhabdomyosarcoma soft tissue sarcoma: a report from Children’s Oncology Group and NRG Oncology study ARST1321. Cancer Chemother Pharmacol. 2022 Apr;89(4):551-557. doi: 10.1007/s00280-022-04397-4. Epub 2022 Jan 27. PubMed PMID: 35083502; PubMed Central PMCID: PMC8958317.
Study ID Citation
Abstract
The use of tyrosine kinase inhibitors for the treatment for soft tissue sarcomas is increasing given promising signals of activity in a variety of tumor types. The recently completed study in non-rhabdomyosarcoma soft tissue sarcomas, ARST1321, demonstrated that the addition of pazopanib to neoadjuvant ifosfamide, doxorubicin, and radiation improved the pathological near complete response rate compared with chemoradiotherapy alone. Pharmacokinetic (PK) evaluation of doxorubicin with pazopanib has not been previously reported. As an exploratory aim, doxorubicin PK data was collected during the dose-finding phase of the study in patients receiving chemotherapy and pazopanib to assess the effect of pazopanib on doxorubicin PK parameters. Blood samples were collected during cycle 2 (week 4) of chemotherapy at the following time points from doxorubicin administration: predose, 5 minutes, 30 minutes, 60 minutes, 2, 4, 8, 24 ± 3, and 48 ± 3 hours after dosing. The population pharmacokinetic and individual post-hoc estimates of doxorubicin and doxorubicinol were determined by nonlinear mixed-effects modeling.