Phase II trial of consolidation docetaxel and samarium-153 in patients with bone metastases from castration-resistant prostate cancer

J Clin Oncol. 2009 May 20;27(15):2429-35. doi: 10.1200/JCO.2008.18.9811. Epub 2009 Apr 13.

Abstract

Purpose: To assess docetaxel combined with samarium-153-ethylene diamine tetramethylene phosphonic acid (EDTMP), a radiopharmaceutical with a high affinity for bone, in patients with castration-resistant prostate cancer (CRPC).

Patients and methods: Patients with bone metastases from CRPC who achieved a response or stabilization after four cycles of docetaxel and estramustine were given consolidation docetaxel 20 mg/m(2)/wk for 6 weeks and samarium-153-EDTMP (37 MBq/kg) during week 1. Prostate-specific antigen (PSA) response was assessed by using consensus criteria, and pain was assessed by using a visual analog scale (VAS). This study used a Simon two-step design with PSA-progression-free survival (PFS) as the primary end point.

Results: Forty-three patients were included in the trial. A PSA response was obtained in 77% (95% CI, 61% to 82%). The pain response rate was 69% (95% CI, 49% to 85%). At least five of the six planned weekly injections of docetaxel were administered to 34 patients (81%). The consolidation docetaxel-samarium-153-EDTMP regimen was well tolerated; there was no febrile neutropenia, and only two episodes (5%) of rapidly reversible grade 3 thrombocytopenia occurred. Although a serum PSA relapse eventually occurred in all patient cases, this regimen resulted in pain control in the long-term. The median PSA-PFS was 6.4 months (95% CI, 6 to 7 months). The median survival was 29 months (95% CI, 22 to 31); the 1-year survival rate was 77% (62% to 87%); and the 2-year survival rate was 56% (41% to 70%).

Conclusion: Combining docetaxel and samarium-153-EDTMP in patients with bone metastases from CRPC is well tolerated, and it yields major pain relief that persists long after treatment. Overall survival compares favorably with that expected in this population of patients, most of whom exhibit symptoms.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Aged
  • Analgesics, Non-Narcotic / administration & dosage
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / secondary*
  • Disease-Free Survival
  • Docetaxel
  • Humans
  • Male
  • Middle Aged
  • Organometallic Compounds / administration & dosage
  • Organophosphorus Compounds / administration & dosage
  • Pain / drug therapy
  • Pain / etiology
  • Pain Measurement
  • Prostate-Specific Antigen / blood
  • Prostate-Specific Antigen / drug effects
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology*
  • Radiopharmaceuticals / administration & dosage
  • Taxoids / administration & dosage

Substances

  • Analgesics, Non-Narcotic
  • Antineoplastic Agents
  • Organometallic Compounds
  • Organophosphorus Compounds
  • Radiopharmaceuticals
  • Taxoids
  • Docetaxel
  • samarium Sm-153 lexidronam
  • Prostate-Specific Antigen