Precision Dosing of Anti-Cancer Medicines for patients undergoing Oncology, Blood Transplant and Cellular Therapies.

This is a prospective, observational study designed to evaluate the pharmacokinetics (PK) of selected precision medicine drugs administered to patients undergoing cancer treatment or conditioning for blood and marrow transplant (BTCT) therapy. The primary aim is to characterize inter-individual variability in drug exposure and explore associations with clinical outcomes, including toxicity and therapeutic response. The observational arm involves the collection of PK, pharmacogenomic, and clinical outcome data across a range of medications used in BTCT and oncology. Clinical data will also be collected from date of enrolment to up to 5 years post treatment to support pharmacokinetic–pharmacodynamic (PK–PD) modelling and to explore exposure–response relationships, using existing records from patients enrolled in prior studies conducted between 2005 and 2025 (listed in Section 4.3). The dataset will encompass patient demographic data, treatment details, PK measurements, toxicity profiles, therapeutic outcomes and relevant laboratory values. For selected agents—such as treosulfan and fludarabine in high-risk patients—therapeutic drug monitoring (TDM) will be used to guide real-time dose adjustments in clinical practice. These interventional components are embedded within routine care and aim to achieve target drug exposures associated with improved efficacy and reduced toxicity, based on emerging evidence and prior research. All dose modifications will be implemented by treating clinicians using validated TDM protocols, with the study team collecting relevant data to evaluate outcomes and inform future precision dosing strategies. Participants will be recruited from oncology and BTCT units at participating institutions. Eligible patients will be those scheduled to receive one or more of the targeted precision medicine drugs as part of their standard clinical care. No changes will be made to the prescribed treatment regimen by the study team. Drug infusion rates are guided by drug-specific prescribing information, clinical guidelines, and may also be protocol-driven. Dose adjustments consider patient factors such as age, body weight, comorbidities, venous access, and fluid status. Dosage is typically based on body surface area or adjusted ideal body weight, with renal and hepatic function also informing modifications. For agents such as busulfan, protocol-specific PK monitoring guides dose, with some protocols requiring attainment of a defined target AUC. All dose modifications will be made solely at the discretion of the treating clinician, in accordance with routine practice and institutional protocols. Blood samples will be collected at predefined time points relative to drug administration to measure plasma concentrations. These samples will be analyzed using validated methods to determine PK parameters such as peak concentration (Cmax), time to peak concentration (Tmax), and area under the curve (AUC). Clinical data—including demographics, organ function, concomitant medications, dose adjustments, and treatment outcomes—will be collected to support PK interpretation. The study will document any dose modifications made during the treatment course, noting the rationale provided by clinicians. These observations will be used to assess whether PK variability may contribute to clinical decision-making and to inform future research on dose optimization strategies.