title: A Phase I/II study of strontium-89 combined with gemcitabine in the treatment of patients with androgen independent prostate carcinoma and bone metastases.
abstract: BACKGROUND
  The objectives of the current study were to determine the maximum tolerated dose and to evaluate the efficacy of gemcitabine given in combination with strontium-89 to patients with androgen independent prostate carcinoma.
  
  
  METHODS
  Patients with androgen-independent prostate carcinoma and painful osteoblastic bone metastases were eligible. On a 12-week course, patients received gemcitabine (600 mg/m(2) or 800 mg/m(2)) on Days 1, 8, 15, 43, 50, and 57. A single dose of strontium-89 (55 microCi/kg) was administered on Day 8.
  
  
  RESULTS
  Fifteen patients were registered, and all were assessable for response and toxicity. Four patients were treated at Dose Level 1 (gemcitabine 600 mg/m(2)) without dose-limiting toxicity. Eleven patients received a total of 13 courses at Dose Level 2 (gemcitabine 800 mg/m(2)). Platelet nadirs of 25000-50000 platelets per microL were common at Dose Level 2, and 1 patient had Grade 4 thrombocytopenia that was dose-limiting. Granulocyte nadirs up to < 500 granulocytes per microL occurred in 4 patients at Dose Level 2 and were reversible. There were no responses, as measured by prostate specific antigen concentration, although 6 patients (40%) had stable disease.
  
  
  CONCLUSIONS
  The authors concluded that 800 mg/m(2) gemcitabine was the maximum tolerated dose for the combination. The study was terminated on the basis that an overall response rate > than 10% was unlikely. Further study at this dose level and schedule is not warranted. .
authors.affiliation: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. lpagliar@mdanderson.org
authors.forename: Lance C
authors.initials: LC
authors.lastname: Pagliaro
authors.forename: Ebrahim S
authors.initials: ES
authors.lastname: Delpassand
authors.forename: Dallas
authors.initials: D
authors.lastname: Williams
authors.forename: Randall E
authors.initials: RE
authors.lastname: Millikan
authors.forename: Shi-Ming
authors.initials: SM
authors.lastname: Tu
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Logothetis
mesh_terms: D000368:Aged; D001859:Bone Neoplasms / Q000556:secondary* / Q000628:therapy*; D002277:Carcinoma / Q000628:therapy; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use* / Q000633:toxicity; D004334:Drug Administration Schedule; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000628:therapy; D017430:Prostate-Specific Antigen / Q000032:analysis; D011471:Prostatic Neoplasms / Q000628:therapy*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use; D013324:Strontium / Q000627:therapeutic use*; D013326:Strontium Radioisotopes / Q000627:therapeutic use*; D013739:Testosterone / Q000494:pharmacology; D000093542:Gemcitabine
chemical_list: D011838:Radiation-Sensitizing Agents; D013326:Strontium Radioisotopes; D003841:Deoxycytidine; D013739:Testosterone; D017430:Prostate-Specific Antigen; C025700:strontium chloride; D013324:Strontium; D000093542:Gemcitabine