Aim: This study was undertaken to validate the first immunoassay for docetaxel (DTX) as a tool for therapeutic dose management. DTX is used in the treatment of many solid tumors and presents a high risk of dose-limiting toxicity. Both pharmacokinetic variability and the association of total exposure with major toxicity have been reported, suggesting therapeutic DTX dose management could benefit patients. The current physical methods for measuring DTX have limited application due to cost, availability and required operator expertise.

Methods: The DTX immunoassay (MyDocetaxel™) developed by Saladax uses a nanoparticle method with a highly selective antibody and can be run on a wide array of clinical chemistry analyzers. The Beckman AU400 and Roche COBAS c111 were used in this study. Performance was evaluated according to CLSI protocols in our laboratory. Precision, accuracy and linearity were validated at 3 external laboratories using the same protocols. Method comparison was performed versus a validated LC-MS/MS method using patient samples (n=89) collected in accordance with IRB approved protocols. These samples, taken at the end of infusion and/or 1 hour post-infusion, may be used to calculate drug exposure.

Results: Linearity was validated from 30ng/mL to 1000ng/mL. Internal studies established the lower limits of detection and quantitation as 21ng/mL and 29ng/mL, respectively. There was no clinically significant bias from co-administered drugs, related compounds or major metabolite. A Deming regression for the method comparison between the immunoassay and LC-MS/MS generated a slope of 0.978 with a y intercept of -1.18ng/mL and a correlation coefficient of 0.9980. For all control concentrations and three patient pools, repeatability was <4% and within-laboratory imprecision was <6%.

Conclusion: With the validation of an immunoassay method, docetaxel testing could gain wider acceptance for individualizing patient dosing with the goal of controlling toxic side effects associated with treatment.