Development and validation of a pharmacokinetically based fixed dosing scheme for suramin

Area of Science:

• Pharmacokinetics and Pharmacodynamics
• Oncology
• Drug Development

Background:

• Suramin is an investigational drug with potential in various cancers.
• Optimizing suramin dosing is crucial for maximizing efficacy and minimizing toxicity.
• Population pharmacokinetic data can inform fixed dosing schedules.

Purpose of the Study:

• To design and evaluate a fixed dosing schedule for suramin.
• To maintain plasma suramin concentrations within a target range (100-300 µg/mL).
• To assess the safety and efficacy of this dosing schedule in patients.

Main Methods:

• A fixed dosing schedule was designed based on population pharmacokinetic estimates.
• Patients received a test dose, loading dose, and subsequent intermittent infusions over 78 days.
• Dosing adjustments were planned based on toxicity and plasma concentrations.

Main Results:

• The fixed dosing schedule was precise, unbiased, and well-tolerated in 42 patients (40 with hormone-refractory prostate cancer).
• No patients discontinued treatment due to excessive suramin concentrations.
• Significant reductions in prostate-specific antigen (PSA) levels were observed in 24/36 assessable patients, with 18 achieving >75% reduction.
• Median survival time was 18.8 months and median time to progression was 10.1 months for HRPC patients.

Conclusions:

• The implemented schedule enabled safe administration of suramin as intermittent bolus injections.
• Suramin toxicity was manageable and reversible.
• The fixed dosing schedule is easily implemented and supports further investigation of suramin in cancer therapy.