title: Functional and pharmacodynamic evaluation of metronomic cyclophosphamide and docetaxel regimen in castration-resistant prostate cancer.
abstract: OBJECTIVE
  The aim of our study was to investigate the association of docetaxel and metronomic cyclophosphamide (CYC) in castration-resistant prostate cancer (CRPC).
  
  
  METHODS
  CRPC xenografts were established with PC3 cells. Mice were treated with a combination of CYC (50 mg/kg/day) and docetaxel (10-30 mg/kg/week) or with docetaxel alone. Docetaxel plasma levels were analyzed in patients receiving the drug alone or combined with CYC.
  
  
  RESULTS
  Metronomic CYC is an effective adjuvant in blocking tumor growth in vivo, with comparable efficacy and less toxic effects compared with docetaxel treatment. CYC acts by downregulating cell proliferation and inducing apoptosis thorough upregulation of p21 and inhibition of angiogenesis. Finally, CYC increases docetaxel plasma levels in patients.
  
  
  CONCLUSIONS
  Metronomic CYC exerts anti-tumoral effects in an in vivo model of prostate cancer and in patients with CRPC, and also increases the bioavailability of docetaxel. These results explain the favorable toxicity and activity profiles observed in patients treated with this regimen.
authors: SAFU Department, Regina Elena National Cancer Institute, Via E. Chianesi 53, Rome, Italy.
authors: Irene
authors: I
authors: Cardillo
authors: Enrico P
authors: EP
authors: Spugnini
authors: Paola
authors: P
authors: Galluzzo
authors: Michela
authors: M
authors: Contestabile
authors: Maria Lucia
authors: ML
authors: Dell'Anna
authors: Mauro
authors: M
authors: Picardo
authors: Stefania
authors: S
authors: Crispi
authors: Raffaele A
authors: RA
authors: Calogero
authors: Maria Teresa
authors: MT
authors: Piccolo
authors: Maddalena
authors: M
authors: Arigoni
authors: Daniela
authors: D
authors: Cantarella
authors: Mariarosaria
authors: M
authors: Boccellino
authors: Lucio
authors: L
authors: Quagliuolo
authors: Gianluigi
authors: G
authors: Ferretti
authors: Paolo
authors: P
authors: Carlini
authors: Alessandra
authors: A
authors: Felici
authors: Francesco
authors: F
authors: Boccardo
authors: Francesco
authors: F
authors: Cognetti
authors: Alfonso
authors: A
authors: Baldi
mesh_terms: D000368:Aged; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D003520:Cyclophosphamide / Q000008:administration & dosage; D000077143:Docetaxel; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008819:Mice, Nude; D020411:Oligonucleotide Array Sequence Analysis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043823:Taxoids / Q000008:administration & dosage; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D043823:Taxoids; D000077143:Docetaxel; D003520:Cyclophosphamide