Single arm open label phase II pilot study of carboplatin in patients with metastatic castration-resistant prostate cancer (CRPC) and PTEN-loss and/or DNA repair defects. PRO-PLAT

Automatisch geschlossen · 2016 bis 2019

Klinische Forschung
Multizentrisch, KSSG als Hauptzentrum
Automatisch geschlossen

Clinical studies in unselected prostate cancer patients strongly support the hypothesis that platinums have anti-tumour activity in some patients with CRPC. For patients progressing after docetaxel based chemotherapy and a novel androgen receptor targeting treatment such as abi-raterone or enzalutamide no standard treatment is available apart from second line chemotherapy with cabazitaxel, which is associated with significant side effects and costs. Additionally it has not formally been tested prospectively in patients after abiraterone/enzalutamide. Carboplatin is a well-known, inexpensive drug that can be easily adminis-tered as weekly short infusion (30min) adapted to renal function and haematological toxicity. The very recently published phase II clinical trial of the PARP inhibitor olaparib in CRPC patients confirms the value of targeting DNA repair defects in a subpopulation of patients. In heavi-ly pre-treated patients with evidence of DNA repair defects by next-generation sequencing techniques the response rate of olaparib reached 88%. The authors concluded that the DNA repair defects reported in the olaparib trial may be associated with platinum sensitivity because platinum compounds exert their antitumour activity through covalent adducts with cellular DNA resulting in DNA damage (G2 phase). The frequency of DNA repair defects was about 33% in the TOPARP trial. {Mateo, 2015 #1061}