Lean Body Mass as a Determinant of Docetaxel Pharmacokinetics and Toxicity

Completed

Conditions: Breast Cancer
Metastatic Castration-resistant Prostate Carcinoma

Interventions: Other: Lean body mass
Other: Total body weight
Other: bloodsampling

Brief Summary: Docetaxel is used as a first line anti-cancer drug in the treatment of several cancers, mainly breast- and metastatic castration-resistant prostate carcinoma.

Anti-cancer drugs are being dosed based on patients estimated Body Surface Area in order to equalize total drug exposure. Nevertheless, docetaxel treatment is characterized by highly interindividual pharmacokinetic variation leading to toxicity and under-treatment.

The investigators will determine which anthropometric parameters, LBM, total body weight (TBW) or BSA correlate best to docetaxel exposure (AUC) for both males and females.

Detailed Description: Docetaxel is used as a first line anti-cancer drug in the treatment of several cancers, mainly breast- and metastatic castration-resistant prostate carcinoma.

Anti-cancer drugs are being dosed based on patients estimated Body Surface Area in order to equalize total drug exposure. Nevertheless, docetaxel treatment is characterized by highly interindividual pharmacokinetic variation leading to toxicity and under-treatment.

For most anti-cancer drugs, including docetaxel, other anthropometric parameters, such as Lean Body Mass (LBM), have been suggested to be superior to Body Surface Are (BSA) as a determinant for dosing but this has not been implemented in clinical practice.

The investigators will determine which anthropometric parameters, LBM, total body weight (TBW) or BSA correlate best to docetaxel exposure (AUC) for both males and females.

The investigators will determine if occurrence of docetaxel toxicity can be related to dose/LBM.

The investigators will determine which methods to measure LBM: DEXA, Bioelectrical Impedance Assessments (BIA) or formula estimates are accurate enough for dosing calculations to be used for dosing docetaxel.

Recruitment & Eligibility

Inclusion Criteria

Subject is at least 18
Subject is able and willing to sign the Informed Consent Form prior to screening evaluations
Female subject diagnosed with breast carcinoma and will receive docetaxel treatment according to standard hospital protocol (TAC regimen) or male subject diagnosed with metastatic castration-resistant prostate carcinoma and will receive docetaxel treatment according to standard hospital protocol (PRODOC regimen)
Subject has a live expectancy of 12 weeks or greater
Absolute neutrophile count (ANC) > 1.5 x 10E9/L
Platelet count > 100 x 10E9/L
Serum creatinine ≤ 2 x ULN
Total bilirubin level < 1.5 x ULN

Exclusion Criteria

Docetaxel treatment within the last year
Moderate or severe liver impairment; [ALAT and/or ASAT ≥ 1.5 ULN] and [AF ≥ 2.5 ULN]
Current therapy with any drug, dietary supplements, or other compounds, or have been used in the last 2 weeks prior to the first docetaxel administration, known to inhibit or induce CYP3A4.
Inability to understand the nature and extent of the study and the procedures required

Arm && Interventions

Group	Intervention	Description
PRODOC regimen	Total body weight	male subject diagnosed with metastatic castration-resistant prostate carcinoma and will receive docetaxel treatment according to standard hospital protocol
PRODOC regimen	bloodsampling	male subject diagnosed with metastatic castration-resistant prostate carcinoma and will receive docetaxel treatment according to standard hospital protocol
TAC regimen	Total body weight	Female subject diagnosed with breast carcinoma and will receive docetaxel treatment according to standard hospital protocol
PRODOC regimen	Lean body mass	male subject diagnosed with metastatic castration-resistant prostate carcinoma and will receive docetaxel treatment according to standard hospital protocol
TAC regimen	Lean body mass	Female subject diagnosed with breast carcinoma and will receive docetaxel treatment according to standard hospital protocol
TAC regimen	bloodsampling	Female subject diagnosed with breast carcinoma and will receive docetaxel treatment according to standard hospital protocol

Primary Outcome Measures

Name	Time	Method
anthropometric parameters related to exposure	within one week prior to first docetaxel dose	To determine which anthropometric parameters, LBM, total body weight (TBW) or BSA correlates best to docetaxel exposure (AUC) for both males and females

Secondary Outcome Measures

Name	Time	Method
relation between docetaxel toxicity and dose/LBM	1 cycle (21 days)	can docetaxel toxicity be related to dose/LBM? docetaxel toxicity is defined as: number of rates of grade 3/4 toxicity, dose delay, dose reduction, treatment termination and combinations of all four as Dose-Limiting Toxicity (DLT)
determine the best method to measure lean body mass	within one week prior to first docetaxel dose	To determine which methods to measure LBM: Bioelectrical Impedance As-sessments (BIA) or formula estimates are accurate enough for dosing calculations to be used for dosing docetaxel. These methods will be compared to the LBM derived from the DEXA scan as the general accepted, accurate and validated method for determining LBM.

Locations (2): Radboud University Nijmegen Medical Centre
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Nijmegen, Netherlands
Deventer Hospital
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Deventer, Netherlands