Optimal Dosing for Targeted Therapies in Oncology
Optimal Dosing for Targeted Therapies in Oncology
Early-stage oncology trials have traditionally used the Maximum Tolerated Dose (MTD) to guide treatment. However, for many targeted therapies, dose-limiting toxicities (DLTs) often don’t appear even at much higher doses, leading to excessive dosing and unnecessary side effects.
A study by Sachs et al. (2016) emphasizes identifying the Biologically Effective Dose (BED) as a complementary strategy. Unlike MTD, BED relies on "effect markers" like target engagement or changes in tumor size to determine the optimal, effective dose that is also safe. For instance, the tyrosine kinase inhibitor cabozantinib was approved at a lower dose than its MTD because patients experienced dose reductions even at the approved level. This shift toward BED ensures that patients receive a dose that is effective without the added burden of unnecessary toxicity.
The study highlights that while MTD-based dosing can be effective for some drugs, many targeted therapies require a more individualized approach, such as using BED. This approach improves treatment outcomes by minimizing side effects, enhancing adherence, and benefiting patients, healthcare providers, and the biopharmaceutical industry. The authors advocate for a multifactorial decision-making process in dose selection to improve efficacy and safety in oncology treatments.
Reference: Sachs JR, Mayawala K, Gadamsetty S, Kang SP, de Alwis DP. Optimal Dosing for Targeted Therapies in Oncology: Drug Development Cases Leading by Example. Clin Cancer Res. 2016;22(6):1318-1324. https://doi.org/10.1158/1078-0432.CCR-15-1295
How True Dose Technology Enhances BED
True Dose technology adds significant value to the BED approach by offering real-time measurements of drug concentration levels in the blood. This monitoring provides a clearer understanding of how much of the drug's active metabolite is in the patient’s system and how it aligns with therapeutic effects. Here’s how True Dose enhances the BED approach:
1. Personalized Dosing: By continuously measuring drug concentrations, True Dose identifies the dose needed for optimal target engagement in each patient. This personalized approach reduces the risk of underdosing (ineffective treatment) or overdosing (increased side effects).
2. Better Understanding of Pharmacokinetics: True Dose provides precise data on how the drug is absorbed, distributed, metabolized, and eliminated. This insight helps find the effective concentration range needed for therapeutic effects without exceeding the BED.
3. Improved Treatment Adherence: With accurate drug level monitoring, clinicians can adjust doses in real-time to maintain optimal concentrations, ensuring patients remain within the therapeutic window. This reduces dose reductions or treatment discontinuation due to side effects, leading to better adherence and outcomes.
4. Enhanced Safety Profile: By keeping drug levels within the BED range, True Dose minimizes exposure to excessive doses, reducing the risk of toxicity and adverse events.
5. Optimizing Dose Adjustments: In cases where patients metabolize drugs differently, True Dose supports informed dose adjustments based on actual drug levels rather than relying on standard dosing, ensuring treatment remains effective and safe.
In summary, True Dose technology enables a more accurate, personalized, and dynamic dosing approach, making identifying and maintaining the Biologically Effective Dose easier. This ultimately improves treatment efficacy, safety, and patient outcomes in oncology.
