title: Metronomic oral cyclophosphamide chemotherapy possibly contributes to stabilization of disease in patients with metastatic castration-resistant prostate cancer: a prospective analysis of consecutive cases.
abstract: BACKGROUND
  Castration-resistant prostate cancer remains a therapeutic challenge, even after establishing the survival benefits of docetaxel chemotherapy. Metronomic chemotherapy stabilizes various cancers through antiangiogenic and immunomodulatory effects. We evaluate the activity of metronomic oral cyclophosphamide chemotherapy in metastatic CRPC patients, and assess predictive factors for clinical outcomes.
  
  
  METHODS
  Twenty-four patients with metastatic CRPC received an oral cyclophosphamide and dexamethasone regimen. Of those, 11 patients (45.8%) had been exposed and resistant to previous docetaxel chemotherapy. Six patients had refused to receive docetaxel chemotherapy, and 7 patients could not receive the therapy because of deteriorated performance status. All patients had already shown resistance to continuous dexamethasone therapy. Demographic and clinical data were collected prospectively.
  
  
  RESULTS
  A total of 16 patients (66.7%) experienced a reduction in PSA levels, and PSA decrease ≥ 50% was observed in 8 patients (33.3%). The median PSA progression-free and overall survival were 5.0 months and 19.0 months, respectively. The favorable PSA decrease had no associations with the progression-free and overall survival, but 7 patients (29.2%) in whom response had exceeded 8 months achieved long overall survival of 28 months in median. None of the patients discontinued therapy because of the presence of toxicities.
  
  
  CONCLUSIONS
  Metronomic cyclophosphamide is an active and well tolerated chemotherapy and can be an option for metastatic CRPC patients. The benefit of this regimen could not always be evaluated according to a favorable PSA decrease; thus, we must identify the predictive factors of response other than known clinical factors.
authors.affiliation: Department of Urology, Dokkyo Medical University, Tochigi, Japan. Electronic address: yashima@dokkyomed.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yashi
authors.affiliation: Department of Urology, Dokkyo Medical University, Tochigi, Japan.
authors.forename: Daisaku
authors.initials: D
authors.lastname: Nishihara
authors.affiliation: Department of Urology, Dokkyo Medical University, Tochigi, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Mizuno
authors.affiliation: Department of Urology, Dokkyo Medical University, Tochigi, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Yuki
authors.affiliation: Department of Urology, Dokkyo Medical University, Tochigi, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Masuda
authors.affiliation: Department of Urology, Dokkyo Medical University, Tochigi, Japan.
authors.forename: Tsunehito
authors.initials: T
authors.lastname: Kambara
authors.affiliation: Department of Urology, Dokkyo Medical University, Tochigi, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Betsunoh
authors.affiliation: Department of Urology, Dokkyo Medical University, Tochigi, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Abe
authors.affiliation: Department of Urology, Dokkyo Medical University, Tochigi, Japan.
authors.forename: Yoshitatsu
authors.initials: Y
authors.lastname: Fukabori
authors.affiliation: Department of Urology, St Luke's International Hospital, Tokyo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Muraishi
authors.affiliation: Department of Urology, Dokkyo Medical University, Tochigi, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Kamai
mesh_terms: D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use*; D003907:Dexamethasone / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D043823:Taxoids / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D018931:Antineoplastic Agents, Hormonal; D043823:Taxoids; D000077143:Docetaxel; D003907:Dexamethasone; D003520:Cyclophosphamide; D017430:Prostate-Specific Antigen
keywords: Clinical outcome; Dexamethasone; Metronomic chemotherapy; Predictive factor; Stabilizing