title: Oral estramustine and cyclophosphamide in patients with metastatic hormone refractory prostate carcinoma: a phase II study.
abstract: BACKGROUND
  Nearly all cases of metastatic prostate carcinoma progress, after hormonal ablation, to a hormone refractory status. To the authors' knowledge no standard chemotherapy for patients with hormone refractory prostate carcinoma (HRPC) exists. In a prospective study, the efficacy and toxicity of an oral combination of estramustine and cyclophosphamide were evaluated.
  
  
  METHODS
  Between March 1996 and April 1998, 32 consecutive patients (median age 74 years; range, 53-84 years) with metastatic HRPC were treated with oral estramustine (10 mg/kg/day) and oral cyclophosphamide (2 mg/kg/day) for 14 days every 28 days. Inclusion criteria were previous complete androgen blockade, antiandrogen withdrawal evaluation, and clinical or biochemical disease progression. Response assessment was based on a decrease > or =50% in the prostate specific antigen (PSA) level associated with improvement (or no worsening) in Eastern Cooperative Oncology Group (ECOG) performance status (PS) and relief of bone pain (if present).
  
  
  RESULTS
  All patients were evaluable for efficacy and toxicity. PSA levels decreased by at least 50% in 14 patients (43.7%) (95% confidence interval, 26.5-60.9), remained stable in 12 patients (37.5%), and rose in 6 patients (18.8%). ECOG PS was 0 in 5 of 14 patients, improved from 1 to 0 in 7 patients, and remained unchanged in 2 patients. Bone pain, present in 8 of 14 patients, disappeared in 7 and was partially relieved in 1. The median duration of response was 30 weeks (range, 8-88+ weeks). An objective partial response was obtained in two cases. Toxicity was mild and mainly gastrointestinal (World Health Organization [WHO] Grade 1). No cases of WHO Grade 3-4 hematologic toxicity occurred.
  
  
  CONCLUSIONS
  The oral combination of estramustine and cyclophosphamide appears to be safe and effective in patients with HRPC. In responding patients its use shows a clinical benefit in terms of improvement of ECOG PS and pain control.
authors.affiliation: Department of Urology, Policlinico Hospital, Perugia, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Bracarda
authors.forename: M
authors.initials: M
authors.lastname: Tonato
authors.forename: P
authors.initials: P
authors.lastname: Rosi
authors.forename: V
authors.initials: V
authors.lastname: De Angelis
authors.forename: E
authors.initials: E
authors.lastname: Mearini
authors.forename: S
authors.initials: S
authors.lastname: Cesaroni
authors.forename: P
authors.initials: P
authors.lastname: Fornetti
authors.forename: M
authors.initials: M
authors.lastname: Porena
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D002277:Carcinoma / Q000188:drug therapy* / Q000556:secondary; D016009:Chi-Square Distribution; D016001:Confidence Intervals; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D018450:Disease Progression; D004961:Estramustine / Q000008:administration & dosage* / Q000009:adverse effects; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000188:drug therapy; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000032:analysis; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D012074:Remission Induction; D012449:Safety
chemical_list: D000726:Androgen Antagonists; D018906:Antineoplastic Agents, Alkylating; D018931:Antineoplastic Agents, Hormonal; D004961:Estramustine; D003520:Cyclophosphamide; D017430:Prostate-Specific Antigen