title: Serum alkaline phosphatase changes predict survival independent of PSA changes in men with castration-resistant prostate cancer and bone metastasis receiving chemotherapy.
abstract: OBJECTIVE
  The association of a change in serum alkaline phosphatase (ALP) with overall survival OS in men with metastatic castration-resistant prostate cancer (CRPC) receiving chemotherapy is unknown. We evaluated the association of changes in ALP within 90 days with OS in men with CRPC and bone metastases treated with docetaxel or mitoxantrone in the TAX327 trial.
  
  
  METHODS
  Eligible patients included those with bony metastatic disease, baseline ALP ≥ 120 u/L (upper limit of normal) and ≥2 post-therapy measurements of ALP available. Survival was estimated using the Kaplan-Meier method and prognostic potential of change in ALP was evaluated using Cox proportional hazards regression. Surrogacy was calculated by the Likelihood Reduction Factor.
  
  
  RESULTS
  601 patients met the eligibility criteria. By day 90, 159 patients had ALP normalization (<120 u/L) and 442 patients did not normalize. Normalization of ALP remained prognostic for OS after adjusting for PSA decline ≥ 30% by day 90 (HR 0.79, 95% CI = 0.65-0.97, P = 0.022). Increase in ALP remained prognostic for OS when adjusting for PSA increase ≥ 50% by day 90 (HR 1.69, 95% CI = 1.33-2.14, P < 0.001). ALP changes did not meet criteria for surrogacy for OS.
  
  
  CONCLUSIONS
  For men with CRPC, bone metastasis and high baseline ALP receiving docetaxel or mitoxantrone chemotherapy, normalization of ALP by day 90 was predictive of better survival independent of ≥30% PSA declines. An increase in ALP by day 90 was also predictive of poor survival independent of ≥50% PSA increase. Given the ready availability of ALP, the validation of our data is warranted.
authors.affiliation: U.S. Oncology Research, Inc., Texas Oncology and Baylor College of Medicine, Webster, TX 77598, USA. guru.sonpavde@usoncology.com
authors.forename: Guru
authors.initials: G
authors.lastname: Sonpavde
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Pond
authors.forename: William R
authors.initials: WR
authors.lastname: Berry
authors.forename: Ronald
authors.initials: R
authors.lastname: de Wit
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Armstrong
authors.forename: Mario A
authors.initials: MA
authors.lastname: Eisenberger
authors.forename: Ian F
authors.initials: IF
authors.lastname: Tannock
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000556:secondary; D000077143:Docetaxel; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D009919:Orchiectomy; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data; D011379:Prognosis; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D012189:Retrospective Studies; D043823:Taxoids / Q000008:administration & dosage; D013997:Time Factors
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D008942:Mitoxantrone; D000469:Alkaline Phosphatase; D017430:Prostate-Specific Antigen