Drug monitoring of sunitinib in patients with advanced solid tumors: a monocentric observational French study |
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Authors: | Luc Cabel Benoit Blanchet Audrey Thomas‐Schoemann Olivier Huillard Audrey Bellesoeur Anatole Cessot Julie Giroux Pascaline Boudou‐Rouquette Romain Coriat Michel Vidal Nathaniel E. B. Saidu Lisa Golmard Jérome Alexandre Francois Goldwasser |
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Affiliation: | 1. Department of Medical Oncology, Cochin Hospital, AP‐HP, Paris, France;2. Paris Descartes University, CARPEM, Paris, France;3. Department of Pharmacocokinetics and Pharmacochemistry, Groupe de Pharmacologie Clinique Oncologique, Cochin Hospital, Paris, France;4. UMR8638 CNRS, UFR de Pharmacie, Université Paris Descartes, PRES Sorbonne Paris Cité, Paris, France;5. U1016 INSERM, UMR 8104 CNRS, UMR‐S1016, Université Paris Descartes, Sorbonne Paris Cité, Paris, France;6. Department of Gastroenterology, Cochin Hospital, AP‐HP, Paris, France;7. Department of Biological pharmacology, Saint‐Louis Hospital, Paris, France |
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Abstract: | Therapeutic drug monitoring (TDM) could be helpful in oral targeted therapies. Data are sparse to evaluate its impact on treatment management. This study aimed to determine a threshold value of plasma drug exposure associated with the occurrence of grade 3–4 toxicity, then the potential impact of TDM on clinical decision. Consecutive outpatients treated with sunitinib were prospectively monitored between days 21 and 28 of the first cycle, then monthly until disease progression. At each consultation, the composite AUC?,ss (sunitinib + active metabolite SU12662) was assayed. The decisions taken during each consultation were matched with AUC?,ss and compared to the decisional algorithm based on TDM. A total of 105 cancer patients and 288 consultations were matched with the closest AUC?,ss measurement. The majority (60%) of the patients had metastatic renal clear‐cell carcinoma (mRCC). Fifty‐five (52%) patients experienced grade 3–4 toxicity. Multivariate analysis identified composite AUC?,ss as a parameter independently associated with grade 3–4 toxicity (P < 0.0001). Using the ROC curve, the threshold value of composite AUC?,ss predicting grade ≥3 toxicity was 2150 ng/mL/h (CI 95%, 0.6–0.79%; P < 0.0001). At disease progression in patients with mRCC, AUC?,ss tended to be lower than the one assayed during the first cycle (1678 vs. 2004 ng/mL/h, respectively, P = 0.072). TDM could have changed the medical decision for sunitinib dosing in 30% of patients at the first cycle of treatment, and in 46% of the patients over the whole treatment course. TDM is routinely feasible and may both contribute to improve toxicity management and to identify sunitinib underexposure at the time of disease progression. |
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Keywords: | oral anticancer agents PK/PD relationship renal‐cell carcinoma sunitinib therapeutic drug monitoring toxicity management |
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