title: Response to second-line chemotherapy in patients with hormone refractory prostate cancer receiving two sequences of mitoxantrone and taxanes.
abstract: OBJECTIVE
  Clinical trials have demonstrated a survival benefit with docetaxel chemotherapy, but limited data exist regarding the activity of second-line chemotherapy.
  
  
  METHODS
  We retrospectively identified all patients at one institution who received at least two chemotherapy regimens for hormone-refractory prostate cancer, one mitoxantrone-based and the other taxane-based, either including docetaxel or paclitaxel. Patients were evaluated using criteria modified from the Prostate-Specific Antigen Working Group.
  
  
  RESULTS
  A total of 68 patients were analyzed; 33 patients received mitoxantrone followed by taxane-based treatment, and 35 received taxane-based chemotherapy followed by mitoxantrone. The median patient age was 66 and 58 years and the median prostate-specific antigen at the start of treatment was 23 and 24 ng/mL in the mitoxantrone-first and taxane-first group, respectively. The response rates to taxane-based chemotherapy were greater whether it was used first or second (P <0.0001). Progression-free survival (PFS) was longer with taxanes than with mitoxantrone, whether used first or second (P <0.05). However, the corresponding total PFS from start of the first regimen to progression during the second regimen was similar at 39.9 and 38.7 weeks (P = 0.67). Overall survival was also not significantly different (15.2 and 17.1 months, P = 0.97). Neither age nor the interval from diagnosis to chemotherapy influenced the differences in PFS.
  
  
  CONCLUSIONS
  Taxane-based chemotherapy is active before or after mitoxantrone. Although PFS was longer with taxane-based chemotherapy, the total PFS and overall survival were equivalent for both sequences in this retrospective analysis, suggesting that taxane-based chemotherapy retains activity, even if delayed. Although responses were seen with mitoxantrone after taxanes, the median PFS was short, and new agents are needed after taxane-based chemotherapy.
authors.affiliation: Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. william_oh@dfci.harvard.edu
authors.forename: William K
authors.initials: WK
authors.lastname: Oh
authors.forename: Judith
authors.initials: J
authors.lastname: Manola
authors.forename: Vladana
authors.initials: V
authors.lastname: Babcic
authors.forename: Neesha
authors.initials: N
authors.lastname: Harnam
authors.forename: Philip W
authors.initials: PW
authors.lastname: Kantoff
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage*; D017239:Paclitaxel / Q000008:administration & dosage*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D012189:Retrospective Studies; D043823:Taxoids / Q000008:administration & dosage*
chemical_list: D000726:Androgen Antagonists; D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D008942:Mitoxantrone; D017239:Paclitaxel