TAXOMET: A French Prospective Multicentric Randomized Phase II Study of Docetaxel Plus Metformin Versus Docetaxel Plus Placebo in Metastatic Castration-Resistant Prostate Cancer.

Docetaxel (DOCE) is a standard of care in metastatic castration-resistant prostate cancer (mCRPC). Several retrospective studies suggested a decrease in Prostate Cancer incidence and mortality with metformin (MET). MET has also demonstrated anti-tumor activity in Prostate Cancer preclinical models, with increased apoptosis when added to DOCE. We aimed at exploring the role of MET in combination with DOCE in mCRPC.

Non-diabetic mCRPC patients were randomly assigned to receive DOCE 75 mg/m2 every 21 days + prednisone (5 mg. BID) with either MET 850 mg BID (D+M) or placebo (D+P) up to 10 cycles. Prostate-Specific Antigen (PSA) response ≥50% from baseline was the primary end point. Secondary end points included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), toxicity and quality of life (QoL).

Out of 99 patients were randomized (D+M = 50; D+P = 49) in 10 French centers. The median follow-up was 86 (IQR 73-88) months. The PSA-response rate reached 66% in the D+M arm, but was not different from that observed in the D+P arm (63%, P = 0,94). In the D+M and D+P arms, the ORR was 28% and 24%, the median PFS was 7.8 and 6.0 months and the median OS was 27 and 20 months (ns), respectively. Diarrhea grade I to II was more frequent in the MET arm (66% vs. 43%). No impairment of QoL was observed.

MET addition failed to improve the standard DOCE regimen in mCRPC. Further research targeting tumor cell metabolism should be performed.

Clinical genitourinary cancer. 2021 Sep 17 [Epub ahead of print]

Marc Pujalte Martin, Delphine Borchiellini, Brice Thamphya, Aline Guillot, Jean-Baptiste Paoli, Dominique Besson, Werner Hilgers, Frank Priou, Claude El Kouri, Benjamin Hoch, Jean-Laurent Deville, Renaud Schiappa, Sandrine Cheli, Gérard Milano, Jean-François Tanti, Frédéric Bost, Jean-Marc Ferrero

Department of Medical Oncology, Centre Antoine Lacassagne, Université Côte d'Azur, Nice, France. Electronic address: ., Department of Medical Oncology, Centre Antoine Lacassagne, Université Côte d'Azur, Nice, France., Research Departement, Epidemiology and Bioinformatics Unit, Centre Antoine Lacassagne, Université Côte d'Azur, Nice, France., Department of Medical Oncology, Lucien Neuwirth Cancer Institute, Saint Priest en Jarez, France., Department of Radiotherapy, Hôpital privé de Clairval, Marseille, France., Department of Medical Oncology, Centre Cario-HPCA, Plérin, France., Department of Medical Oncology, Sainte Catherine Cancer Institute, Avignon Provence, France., Department of Medical Oncology, CHD Vendée, La Roche sur Yon, France., Department of Medical Oncology, Centre Catherine de Sienne, Nantes, France., Department of Medical Oncology, Centre Azuréen de Cancérologie, Mougins., Department of Medical Oncology, APHM - CHU Timone, Marseille, France., Clinical Research and Innovation Department, Centre Antoine Lacassagne, Université Côte d'Azur, Nice, France., Oncopharmacology Unit, EA3836, Centre Antoine Lacassagne, Université Côte d'Azur, Nice, France., Inserm U1065, C3M, Université Côte d'Azur, Nice, France.

email news signup