title: Sequential mitoxantrone/prednisone followed by docetaxel/estramustine in patients with hormone refractory metastatic prostate cancer: results of a phase II study.
abstract: BACKGROUND
  Mitoxantrone/prednisone ameliorates symptoms in hormone refractory prostate cancer (HRPC) but has no effect on survival. Docetaxel (Taxotere)/estramustine improves response but with significant toxicity. We reasoned that a sequential administration of the two regimens could be a viable alternative for delivering full doses of chemotherapy, avoiding overlapping toxicity and preserving dose intensity.
  
  
  METHODS
  Thirty HRPC patients were treated with mitoxantrone 10 mg/m(2), day 1, every 3 weeks, plus prednisone 5 mg twice daily, for three cycles, followed by estramustine phosphate, 280 mg three times daily, days 1 to 5, plus docetaxel 75 mg/m(2), day 2, every 3 weeks for a maximum of 10 cycles.
  
  
  RESULTS
  All patients were assessable for response and toxicity. After mitoxantrone/prednisone treatment, the prostate-specific antigen (PSA) response rate was 23%, which increased to 63% after completion of sequential mitoxantrone/prednisone and docetaxel/estramustine treatment (12 partial and 7 complete responses). With a median follow-up of 18 months, median survival for all patients was 18 months, and median progression-free survival was 10 months. The mitoxantrone/prednisone regimen was well tolerated, and the only grade 3-4 toxicity was grade 3 neutropenia in four (13%) patients. Twenty-nine patients received a total of 173 cycles of docetaxel/estramustine (median, 6 cycles/patient). Six (20%) patients had grade 3-4 neutropenia and two (6%) patients had febrile neutropenia episodes. The most frequent non-hematological toxic effects were asthenia, nausea and vomiting, edemas and onycholysis. Two (6%) patients had deep venous thrombosis.
  
  
  CONCLUSIONS
  Mitoxantrone/prednisone followed by docetaxel/estramustine is a well-tolerated and active regimen in HRPC. Sequential therapy is feasible and can be used to integrate novel, more active regimens.
authors.affiliation: Medical Oncology Service, Institut Català d'Oncologia, Hospital Germans Trias i Pujol, Carretera del Canyet, s/n, 08916 Badalona, Barcelona, Spain. afont@ns.hugtip.scs.es
authors.forename: A
authors.initials: A
authors.lastname: Font
authors.forename: A
authors.initials: A
authors.lastname: Murias
authors.forename: F R García
authors.initials: FR
authors.lastname: Arroyo
authors.forename: C
authors.initials: C
authors.lastname: Martin
authors.forename: J
authors.initials: J
authors.lastname: Areal
authors.forename: J J
authors.initials: JJ
authors.lastname: Sanchez
authors.forename: J A
authors.initials: JA
authors.lastname: Santiago
authors.forename: M
authors.initials: M
authors.lastname: Constenla
authors.forename: J M
authors.initials: JM
authors.lastname: Saladie
authors.forename: R
authors.initials: R
authors.lastname: Rosell
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000077143:Docetaxel; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D004961:Estramustine / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D011241:Prednisone / Q000008:administration & dosage; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D004961:Estramustine; D008942:Mitoxantrone; D017430:Prostate-Specific Antigen; D011241:Prednisone