title: Metronomic cyclophosphamide therapy in hormone-naive patients with non-metastatic biochemical recurrent prostate cancer: a phase II trial.
abstract: After curative local therapy, biochemical recurrence is a mode of relapse among patient with prostate cancer (PC). Deferring androgen deprivation therapy (ADT) or offering non-hormonal therapies may be an appropriate option for these non-symptomatic patients with no proven metastases. Metronomic cyclophosphamide (MC) has shown activity in metastatic PC setting and was chosen to be assessed in biochemical relapse. This prospective single-arm open-label phase II study was conducted to evaluate MC regimen in patients with biochemical recurrent PC. MC was planned to be administered orally at a daily dose of 50 mg for 6 months. Primary endpoint was PSA response. Thirty-eight patients were included and treated. Median follow-up was 45.5 months (range 17-100). Among them, 14 patients (37 %) achieved PSA stabilisation and 22 patients (58 %) experienced PSA progression. Response rate was 5 % with one complete response (2.6 %), and 1 partial response with PSA decrease >50 % (2.6 %). The median time until androgen deprivation therapy initiation was around 15 months. The treatment was well tolerated. Neither grade 3-4 toxicity nor serious adverse events were observed. This first prospective clinical trial with MC therapy in patients with non-metastatic biochemical recurrence of PC displayed modest efficacy when measured with PSA response rate, without significant toxicity. It might offer a new safe and non-expensive option to delay initiation of ADT. These results would need to be confirmed with larger prospective randomised trials.
authors.affiliation: Department of Medical Oncology, CHRU Minjoz, Besançon, France. fabien.calcagno@gmail.com.|UMR1098, SFR IBCT, University of Franche-Comté, Besançon, France. fabien.calcagno@gmail.com.|Clinical Investigation Center, Inserm CIC1431, Besançon, France. fabien.calcagno@gmail.com.
authors.forename: Fabien
authors.identifier: http://orcid.org/0000-0003-1455-3776
authors.initials: F
authors.lastname: Calcagno
authors.affiliation: Department of Medical Oncology, CHRU Minjoz, Besançon, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Mouillet
authors.affiliation: Department of Medical Oncology, CHRU Minjoz, Besançon, France.|INSERM, UMR1098, Besançon, France.|UMR1098, SFR IBCT, University of Franche-Comté, Besançon, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Adotevi
authors.affiliation: Department of Medical Oncology, CHRU Minjoz, Besançon, France.
authors.forename: Tristan
authors.initials: T
authors.lastname: Maurina
authors.affiliation: Department of Medical Oncology, CHRU Minjoz, Besançon, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Nguyen
authors.affiliation: Department of Medical Oncology, CHRU Minjoz, Besançon, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Montcuquet
authors.affiliation: Department of Medical Oncology, CHRU Minjoz, Besançon, France.|INSERM, UMR1098, Besançon, France.|UMR1098, SFR IBCT, University of Franche-Comté, Besançon, France.
authors.forename: E
authors.initials: E
authors.lastname: Curtit
authors.affiliation: INSERM, UMR1098, Besançon, France.|UMR1098, SFR IBCT, University of Franche-Comté, Besançon, France.|Department of Urology, CHRU Minjoz, Besançon, France.
authors.forename: F
authors.initials: F
authors.lastname: Kleinclauss
authors.affiliation: Department of Medical Oncology, CHRU Minjoz, Besançon, France.|INSERM, UMR1098, Besançon, France.|UMR1098, SFR IBCT, University of Franche-Comté, Besançon, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Pivot
authors.affiliation: Department of Medical Oncology, CHRU Minjoz, Besançon, France.|INSERM, UMR1098, Besançon, France.|UMR1098, SFR IBCT, University of Franche-Comté, Besançon, France.|Clinical Investigation Center, Inserm CIC1431, Besançon, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Borg
authors.affiliation: Department of Medical Oncology, CHRU Minjoz, Besançon, France.|INSERM, UMR1098, Besançon, France.|UMR1098, SFR IBCT, University of Franche-Comté, Besançon, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Thiery-Vuillemin
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality; D059250:Administration, Metronomic; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage*; D018572:Disease-Free Survival; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality
chemical_list: D000970:Antineoplastic Agents; D003520:Cyclophosphamide; D017430:Prostate-Specific Antigen
keywords: Biochemical recurrence; Cyclophosphamide; Hormone-naive; Metronomic chemotherapy; Non-metastatic; Prostate cancer