Feasibility of a Chemotherapy With Docetaxel-Prednisone for Castration-resistant Metastatic Prostate Cancer Elderly Patients (GERICO10)

• Feasibility of 2 different protocols of Docetaxel chemotherapy [ Time Frame: Up to 18 weeks (6 cycles of chemotherapy) ] [ Designated as safety issue: Yes ]

  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)
  
  

• Overall Survival [ Time Frame: From randomization until death for any cause or last follow-up news (censored data) ] [ Designated as safety issue: Yes ]
  Overall Survival is defined as the time from randomization until death for any cause or last follow-up news (censored data).
  
  
• Geriatric evaluation [ Time Frame: At baseline, D1 of Cycle 1 and Cycle 4, at the end of treatment and at follow-up visits ] [ Designated as safety issue: No ]

  The impact of the chemotherapy will be evaluated on Comprehensive Geriatric Assessment :

  • Test de screening G8
  • Cumulative Illness Rating Scale(CIRSG)
  • Folstein Mini Mental State (MMS)
  • Activity of Daily Living (ADL)
  • Instrumental Activity of Daily Living (IADL)
  • Geriatric Depression Scale (GDS)
  • Mini Nutritionnal Assessment (MNA)
  
  
• Number of patients with Adverse Events [ Time Frame: At baseline, D1 of each cycle , at the end of treatment and at the follow-up visits ] [ Designated as safety issue: Yes ]
  Tolerance and safety will be assessed through recording of adverse events using NCI-CTCAE toxicity classification V4.0.
  
  
• Quality of Life [ Time Frame: At baseline, D1 of the Cycle 4, at the end of the treatment and at the follow-up visits ] [ Designated as safety issue: No ]
  The impact of the chemotherapy is evaluated on the European Organisation for Research and Treatment of Cancer (EORTC) Quality Of Life - Questionnaire - QLQ-C30
  
  
• Vital signs measurement [ Time Frame: At baseline, D1 of each cycle , at the end of treatment and at the follow-up visits ] [ Designated as safety issue: Yes ]
  Tolerance and safety will be assessed through vital signs measurement.
  
  
• Prostate-specific antigen (PSA) measurements [ Time Frame: At baseline, D1 of each cycle , at the end of treatment and at the follow-up visits ] [ Designated as safety issue: No ]
  Efficacy will be assessed through monitoring PSA values
  
  

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 the followings:

• 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.