Background: Docetaxel is used as first line chemotherapy for metastatic castrate resistant prostate cancer (mCRPC). It has been reported that castrated men have substantially increased docetaxel clearance (CL) compared to uncastrated men treated for mCRPC (Franke et al, J Clin Oncol 28: 4562−7, 2010). These results were obtained from 20 castrated men, with 10 non-castrated men serving as controls. In this study, we aimed to validate these findings in a larger and independent cohort of patients. Material and Methods: All male patients treated within the context of a pharmacokinetic study (Dutch Trial Registry; NTR2311) with docetaxel for solid tumors were included in this analysis (n = 74). As chemotherapy alone does not result in alterations in testosterone levels, out of these 74 patients, all men with non-prostate tumors served as controls (n = 36) of the castrated mCRPC patients (n = 38). Five of these control patients received docetaxel in combination with SU014813 in a clinical phase I study, all other patients received monotherapy. SU014813 has no clinically relevant pharmacokinetic (PK) interaction with docetaxel (de Jonge et al, Eur J Cancer 47: 1328−35, 2011). Dosage ranged from 30mg/m to 100mg/m, given in different schedules. Plasma docetaxel levels were determined by HPLC or LC-MS/MS. Individual PK parameters were estimated from previously developed population PK models by non-linear mixed effects modelling using NONMEM software. P-values were calculated using an independent samples T-test, while linear regression analysis was used to adjust for age, ethnicity, body surface area, concomitant use of other anticancer drugs, and dose when analysing haematological toxicity. Results: In the castrated patients, there was an increased docetaxel CL compared to the CL of uncastrated men (48.4 L/h versus 42.1 L/h, P = 0.051). In addition, both absolute neutrophil count nadir (n = 66) and white blood cell count nadir (n = 68) were significantly higher in castrated patients during chemotherapy with docetaxel (4.1 versus 1.7 ×109/L, P = 0.003 and 5.3 versus 3.1×109/L, P = 0.016, respectively). Conclusions: Androgen deprived prostate cancer patients in this study show an increased CL. In addition, castrated patients show less pronounced haematological toxicity compared to the control group of uncastrated men treated with docetaxel. Adding these results to the existing knowledge provides a solid foundation for further investigations regarding the increase in clearance related to castration-status and also for the individualization of docetaxel treatment in male patients.