Abstract 2588: Antiangiogenic and immunomodulatory effects of metronomic cyclophosphamide (CPM) treatment in prostate cancer patients with PSA failure
Authors: Adotevi Olivier , Calcagno Fabien , Maurina Tristan , Kim Stefano , Thiery-Vuillemin Antoine , Borg Christophe , Godet Yann , Laheurte Caroline 
Published: May 2015

Background: After curative local therapy, patients (pts) will experience rising PSA as an early indicator of recurrent prostate cancer and no standard of care exists. Previous studies demonstrated the clinical interest of cyclophosphamide metronomic chemotherapy (CMC) in several cancers. Multifactorial modes of action including immunological and anti-angiogenic effects have been well described by Kerbel et al and Ghiringhelli et al (Cancer Research 2006 and European Journal of immunology 2004, respectively). In the current study, we investigated the safety and immuno-modulatory effects of CMC in prostate cancer patients with PSA failure (biochemical relapse).

Methods: We conducted a prospective phase II study to characterize the clinical and immunological interest of CMC in histologically proven prostate cancer patients previously treated by prostatectomy and with biochemical relapse (defined as PSA &gt; 1 and &lt; 20ng/mL and progressive PSA level on 3 different measures). CMC was administered per os, at daily dose of 50 mg during 6 months. PSA level, serum VEGF and immune parameters were monitored every month in blood samples.

Results: Thirty-four consecutive pts were enrolled in this study and all received CMC. The median age was 68,3 (range, 56,9-82,1) and all pts had good performance status (ECOG-PS = 0). Gleason Score was 7 in 58%, ≤6 in 13%, and ≥ 8 in 13%. No serious adverse events (grade 3-5) were observed. The most common drug-related adverse event was grade 1 lymphopenia. Baseline PSA was 2,92 ng/mL (range, 1,1-9,35). Twenty-two pts presented stable PSA (64.7%), one patient had partial response defined by &gt;50% decline in the serum PSA (3%), and 11 pts (32%) had PSA progression before 6 months. The immuno-monitoring performed in all pts who completed 6 months CMC. A decrease of immunosuppressive regulatory T cells (Treg) was observed in 56% (10/18). In addition, high rate of activated HLA-DR+ cytotoxic CD8 T cells was also detected in these pts. Furthermore, serum VEGF level decreased at month 1 but it returned to baseline level at the end of treatment in 9/17 pts evaluated (52%). In some patients the correlation was observed between the control of PSA level, the decrease of Treg and VEGF parameters.

Conclusions: This study demonstrated the clinical benefit and the ability of CMC to promote the blockage of angiogenesis and immuno-modulatory effect in prostate cancer patients treated for a biochemical relapse. It will be of interest to combine CMC to vaccination in these patients.

Citation Format: Olivier Adotevi, Fabien Calcagno, Tristan Maurina, Stefano Kim, Antoine Thiery-Vuillemin, Christophe Borg, Yann Godet, Caroline Laheurte. Antiangiogenic and immunomodulatory effects of metronomic cyclophosphamide (CPM) treatment in prostate cancer patients with PSA failure. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2588. doi:10.1158/1538-7445.AM2014-2588