SOCRA 2024 Annual Conference Program Book - Flipbook - Page 55
The Modern Sophistry
Most new
oncology drugs
now are
targeted
The wisemen who used rhetoric to
persuade crowds rather than to pursue the
truth…
Premise #1: Anticancer drugs work best at
MTD
Premise #2: MTA are anticancer drugs
Fallacy: MTA work best at MTD
Protagoras
Thrasymachus
Gorgias
MTD maximum tolerated dose
MTA molecularly targeted agents
Cytoxic paradigms don’t apply to MTA
Cytotoxics (IV)
MTA (Oral)
Narrow
Wider
Finding the right balance: efficacy/toxicity
PK variability
Therapeutic range
Shorter
Longer
Dose‐response curve
Length of therapy
Steep/Linear
Flatter/Non‐linear
Dose
Close to MTD
Dose range
Only ≥ G3 toxicities
Short DLT window
G2 diarrhea?
Longer DLT window?
Delta for efficacy
DLT definition/window
Delta for toxicity
Drug activity across dose levels
Comprehensive PK/PD
Hallmarks of
variability in
PK exposure of
oral targeted
agents in
oncology
Dose‐response and Exposure‐
response relations
Dose optimization
What studies aiming at
MTD are often missing
Low grade toxicities: dose
interruptions, modifications…
*MTD Maximum Tolerated Dose
Groenland ASCO Educat Book 2021
- 55 -
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