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

MET could increase the cytotoxicity effect of DOCE against PC3 prostate cancer cells and reduce cancer-related mortality in retrospective study . TAXOMET study randomized 99 non-diabetic metastatic castration-resistant prostate cancers: 50 pts in docetaxel-metformin combination vs. 49 patients in docetaxel plus placebo. With a median follow-up of 86 months, MET addition failed to improve the standard DOCE regimen. Background: 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. Patients and Methods: Non-diabetic mCRPC patients were randomly assigned to receive DOCE 75 mg/m 2 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), toxicit y and qualit y of life (QoL). Results: 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. Conclusion: MET addition failed to improve the standard DOCE regimen in mCRPC. Further research targeting tumor cell metabolism should be performed. [ABSTRACT FROM AUTHOR]