Hedgehog inhibitors for basal cell carcinoma cause significant side effects like dysgeusia and muscle cramps. To improve tolerability and long-term adherence, clinicians use practical strategies like scheduled treatment interruptions (e.g., weeks on, weeks off) rather than continuous daily dosing.

To manage Dasatinib's common side effect of pleural effusions, a randomized study showed that skipping doses on weekends is superior to dose reduction. This strategy leverages the drug's short half-life, maintaining peak levels for efficacy while providing a break from off-target effects that cause toxicity.

To improve long-term tolerability of amivantamab, some experts advocate for a "marathon, not a sprint" approach. This involves aggressive dose holds or reductions at the earliest signs of toxicity, even low-grade, to prevent side effects from escalating and ensure patients can remain on effective therapy longer.

In the REJOYCE ovarian-1 trial for RDXD, the 5.6 mg/kg dose was selected to move forward over a 6.4 mg/kg dose that showed a higher response rate (57%). The lower dose had significantly fewer serious adverse events and a lower rate of interstitial lung disease (ILD), demonstrating a crucial trade-off where safety and tolerability outweigh peak efficacy in late-stage development.

For patients who achieve a deep response to a PARP inhibitor but struggle with persistent hematologic toxicity despite dose reductions, a practical clinical strategy is to switch to a different agent within the same class (e.g., from olaparib to rucaparib). This may offer a chance for improved tolerability while maintaining therapeutic benefit.

When managing ocular toxicity from the ADC mirvetuximab, clinicians advocate for delaying the subsequent dose to allow the cornea to heal naturally. This approach is often preferred over an immediate dose reduction, which might unnecessarily compromise the treatment's efficacy.

The REJOICE trial for an ADC in ovarian cancer exemplifies a critical trend: embedding multi-arm dose optimization studies. This approach identified a dose that maintained high response rates (57%) while significantly lowering rates of serious adverse events like ILD (from 6% to 3%), prioritizing patient safety.

A majority of patients on the lenvatinib/pembrolizumab regimen require dose reductions due to toxicity. Crucially, clinical trial data shows no significant change in progression-free survival for patients on lower doses, an important point for patient reassurance.

Clinicians recommend starting lenvatinib at the full 20mg dose rather than escalating from a lower dose. This ensures therapeutic levels are reached. They then dose-reduce aggressively as needed. Starting low risks falsely concluding the drug is ineffective if the patient tolerates a suboptimal dose without response.