Randomized Phase II Study Evaluating the Feasibility of a Chemotherapy With Docetaxel-Prednisone in a Weekly Schedule or Every 3 Weeks, for Castration-resistant Metastatic Prostate Cancer Elderly Patients (>=75), "Vulnerable" or "Frail" , as Defined by the Criteria of the International Society of Geriatric Oncology (SIOG)
Standard management of castration-resistant metastatic prostate cancer is represented by
chemotherapy with Docetaxel 75 mg/m² every 3 weeks combined with Prednisone since a
symptomatic and overall survival benefit was demonstrated.
Although this benefit is independent of age in the study by Tannock (cut-off:69), it does
not seem possible to extrapolate these results, obtained in a selected population, to the
majority of patients we encounter in daily practice, >= 75 years old and / or unfit.
Retrospective studies have shown that chemotherapy was feasible, at standard or adapted
doses in an unselected elderly population with good results in terms of tolerance and
efficacy over symptoms.
Our study aims to evaluate prospectively the feasibility of a chemotherapy with
Docetaxel/Prednisone administered every 3 weeks (60 mg / m² at D1C1 then 70 mg / m² at D1
for subsequent cycles if tolerance is good) or weekly (35mg / m² at D1 and D8 with Day 1 =
Day 21) to patients >= 75 years old, evaluated by comprehensive geriatric assessment,
belonging to group 2 "vulnerable" or to group 3 "frail" of the classification proposed by
the International Society of Geriatric Oncology (SIOG).
Feasibility is defined as the possibility for a patient to receive 6 cycles of chemotherapy
without withdrawal. Reasons for study withdrawal were defined by the GERICO Group and are
- stop or delay of chemotherapy > 2 weeks
- Necessity to reduce the dose of chemotherapy > 25 %
- febrile neutropenia or non-haematological grade 3 toxicity (except alopecia) according
to NCI-CTCAE V4.0.
- Geriatric criterion (Activity of Daily Living (ADL) decrease >= 2 points)
The statistical methodology used is a double randomized phase II after stratification
according to the SIOG criteria, based on a Simon Optimum plan.
A pharmacokinetic / pharmacodynamic study is associated to our project, based on a method of
population pharmacokinetic. The aim is to highlight predictors of the haematological
tolerance of this chemotherapy by evaluating clinical, geriatric and biological parameters.
The results of this study will support the terms of prescription of chemotherapy, in
patients aged 75 and over, classified as "vulnerable" or "frail" regarding SIOG criteria,
with defined geriatric assessment.
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Feasibility of 2 different protocols of Docetaxel chemotherapy
Main criteria is the rate of patients receiving 6 cycles of treatment without experiencing any of the following criteria: Stop or delay of chemotherapy > 2 weeks Necessity to reduce the dose of chemotherapy > 25 % Febrile neutropenia or non-haematological grade 3 toxicity (except alopecia)according to NCI-CTCAE V4.0 Geriatric criterion ( ADL decrease >= 2 points)
Up to 18 weeks (6 cycles of chemotherapy)
Institut Claudius Regaud
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)