Pharmacokinetically guided sunitinib dosing: a feasibility study in patients with advanced solid tumours

Area of Science:

• Pharmacology
• Oncology
• Clinical Pharmacy

Background:

• Sunitinib plasma exposure exhibits significant inter-individual variability.
• This variability necessitates personalized dosing strategies for optimal therapeutic outcomes.

Purpose of the Study:

• To assess the safety and feasibility of adjusting sunitinib dosage based on pharmacokinetic (PK) levels.
• To determine if PK-guided dosing can achieve target plasma concentrations without increasing toxicity.

Main Methods:

• A prospective study involving patients treated with sunitinib 37.5 mg daily.
• Plasma trough levels of sunitinib and N-desethyl sunitinib were measured on days 15 and 29.
• Dose adjustments were made based on total trough levels (TTL) and toxicity: dose increased by 12.5 mg if TTL < 50 ng/mL and no grade ≥3 toxicity, or decreased if grade ≥3 toxicity occurred.

Main Results:

• Twenty-nine of 43 patients were evaluable for PK.
• Grade ≥3 adverse events occurred in 24% at the starting dose and 31% after dose escalation.
• 15 patients (52%) had below-target TTL at the start; 5 of these (17% of total) reached target TTL after dose escalation without increased toxicity.

Conclusions:

• Dose escalation based on PK levels is feasible in a subset of patients.
• A PK-guided dosing strategy may improve sunitinib exposure and potentially clinical outcomes.
• This approach could form the basis for future clinical practice implementation.