Agema Bram C, Koch Birgit C P, Mathijssen Ron H J, Koolen Stijn L W
Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands.
Rotterdam Clinical Pharmacometrics Group, Rotterdam, The Netherlands.
Drugs. 2025 Apr;85(4):487-503. doi: 10.1007/s40265-025-02152-6. Epub 2025 Feb 12.
One dose does not fit all, especially in oncolytic drugs, where side effects and therapy failures highlight the need for personalized dosing approaches. In recent years, the quest to apply model-informed precision dosing to oncology drugs has gained significant momentum, reflecting its potential to revolutionize patient care by tailoring treatments to individual pharmacokinetic profiles. Despite this progress, model-informed precision dosing has not (yet) become widely integrated into routine clinical care. We aimed to explain model-informed precision dosing from a clinical viewpoint while addressing all prospective model-informed precision dosing implementation and validation studies in the field of oncology. We identified 16 different drugs for which prospective model-informed precision dosing validation/implementation has been performed. Although these studies are mostly focused on attaining adequate drug exposures and reducing inter-individual variability, improved clinical outcomes after performing model-informed precision dosing were shown for busulfan, and high-dose methotrexate. Toxicities were significantly reduced for busulfan and cyclophosphamide treatment. In contrast, for carboplatin, for which model-informed precision dosing has been used in the Calvert formula, no prospective validation on outcomes was deemed necessary as the therapeutic window had been extensively validated. Model-informed precision dosing has shown to be of added value in oncology and is expected to significantly change dosing regimens in the future.
一种剂量并不适用于所有人,尤其是在溶瘤药物方面,其副作用和治疗失败凸显了个性化给药方法的必要性。近年来,将模型指导的精准给药应用于肿瘤药物的探索已取得显著进展,这反映出其通过根据个体药代动力学特征定制治疗方案,有可能给患者护理带来变革。尽管取得了这一进展,但模型指导的精准给药尚未广泛纳入常规临床护理。我们旨在从临床角度解释模型指导的精准给药,同时探讨肿瘤学领域所有前瞻性模型指导的精准给药实施和验证研究。我们确定了16种已进行前瞻性模型指导的精准给药验证/实施的不同药物。尽管这些研究大多侧重于实现足够的药物暴露和减少个体间差异,但对于白消安和大剂量甲氨蝶呤,模型指导的精准给药后显示出改善的临床结果。白消安和环磷酰胺治疗的毒性显著降低。相比之下,对于已在卡尔弗特公式中使用模型指导的精准给药的卡铂,由于其治疗窗口已得到广泛验证,因此认为无需对结果进行前瞻性验证。模型指导的精准给药已显示在肿瘤学中具有附加价值,预计未来将显著改变给药方案。