Optimizing intermittent dosing of oral small molecule inhibitors.

In 30 seconds

This systematic review assessed evidence on intermittent or alternative dosing of oral small molecule inhibitors, including guidance for dose optimization and treatment personalization. The review included 55 trials identified through a PubMed search; 33 were phase 1 trials. Most studies involved agents for solid tumours, particularly renal cell carcinoma, and sunitinib was the most frequently examined drug. Twenty-eight trials compared dosing strategies, with 26 assessing efficacy and 27 assessing safety. The authors concluded that available evidence provides limited guidance for clinicians seeking to optimize intermittent dosing.

Key findings

• The review included 55 trials, of which 33 were phase 1 trials.
• Twenty-eight trials compared dosing strategies; 26 examined efficacy outcomes and 27 examined safety outcomes.
• Most trials concerned solid tumours, particularly renal cell carcinoma, and sunitinib was the most frequently studied agent.
• The review found limited guidance for optimizing intermittent dosing of oral small molecule inhibitors.

Why it matters

Oral small molecule inhibitors have varied mechanisms and pharmacokinetic considerations, making dose selection more complex than for traditional chemotherapy. This review indicates that evidence comparing alternative schedules exists, but remains insufficient to provide broad guidance for dose optimization or personalization when treatment toxicities arise.

What to keep in mind

The review reports limited guidance in the available literature; its evidence base comprised trials with varied agents and dosing comparisons, and most trials were phase 1.