Metformin-Docetaxel Association in Metastatic Hormone-refractory Prostate Cancer
Status:
Completed
Trial end date:
2018-05-31
Target enrollment:
Participant gender:
Summary
Prostate cancer is the second leading cause of mortality in men, representing 10 deaths about
of 100 cancers (INVS 2009). Treatment for metastatic prostate cancer, when becoming resistant
to hormone-treatment, is mostly resumed to a relatively ineffective chemotherapy
(Docetaxel/TAXOTERE®) (1). Recently, numerous clinical and preclinical works showed that
Metformin could represent an excellent candidate for treatment of advanced prostate cancer.
This is a widely prescribed drug, for type 2 diabetes, with clinical advantage of exhibiting
very rare serious side effects. On the other hand, the use of this molecule in patients was
associated with a decrease of tumors incidence, in particular prostate cancer (2). Numerous
in vitro and in vivo studies support its role as an anti-cancer drug, in several cell lines
(3). These experimental results are consistent with a clinical trial pilot study, performed
in colorectal cancer, showing anti proliferative effect of Metformin (4). In the field of
prostate, F. Bost in J.F. Tanti's team (INSERM U895, Nice) demonstrated that Metformin
inhibits cell viability of human prostate cancer cells, via mTOR downregulation and decrease
tumor growth in a xenograft model (5). Furthermore, preclinical data performed by this team
showed that Metformin increased significantly apoptosis induced by TAXOTERE®. Therefore, by
targeting specifically cancer cell metabolism, Metformin offers new promising therapeutic
strategy.
The primary objective of this randomized study is to evaluate the biological efficacy of
Metformin combination with TAXOTERE® in patients with metastatic hormone-refractory prostate
cancer. To achieve this purpose, PSA response rate will be evaluated according to ASTRO
definitions (Bubley, Carducci et al. 1999). Concurrently, secondary endpoints will be under
investigation in order to evaluate the clinical response according to RECIST criteria, the
overall and free-progression survival and the quality of life. Toxicity assessment will also
be performed regarding to this drug combination.
Considering the well tolerability of Metformin and the first clinical and pre-clinical data
reports of it use in cancer treatment, combining Docetaxel (TAXOTERE®) with Metformin may
represent a promising strategy for treatment of hormone-refractory prostate cancer.