title: A phase II trial of androgen deprivation therapy (ADT) plus chemotherapy as initial treatment for local failures or advanced prostate cancer.
abstract: OBJECTIVE
  Long-term hormonal ablation in prostate cancer is associated with decreased overall health and quality of life. Few reports emphasized the role of chemotherapy in the management of early stage prostate cancer. This study analyzed the safety and efficacy of androgen deprivation therapy (ADT) plus chemotherapy as initial treatment for patients identified as local failures or not eligible for prostatectomy or radiation therapy due to advanced disease presentation.
  
  
  METHODS
  Enrolled patients received ADT in the form of leuprolide every 12 weeks for 24 months with bicalutamide initiating after the completion of chemotherapy. Chemotherapy consisted of ketoconazole and doxorubicin for weeks 1, 3, and 5 and estramustine and docetaxel and for weeks 2, 4 and 6. During weeks 7 and 8, no treatment was received.
  
  
  RESULTS
  Forty-six patients were enrolled, and forty-five patients were evaluable. Median progression-free survival (PFS) was 23.4 months. Median overall survival (OS) was 53.7 months. Out of 45 patients with measurable disease, 22 patients had an objective response: 9 patients achieved a complete response; 2 patients achieved a partial response; 10 patients achieved stable disease. Frequent grade 3 adverse events included elevated ALT (17 %), hypokalemia (13 %), and hypophosphatemia (13 %). Grade 4 adverse events were rare and included low bicarbonate (2 %), hypokalemia (2 %), leukocytopenia (2 %), and neutropenia (2 %).
  
  
  CONCLUSIONS
  The treatment demonstrated clinical benefit in all patient subsets with minimal reversible treatment-related adverse events. Subgroup analysis suggests that having prior local therapy resulted in greater PFS and OS.
authors.affiliation: Division of Oncology, Department of Internal Medicine, University of Texas Health Science Center at Houston (Medical School)/Memorial Hermann Cancer Center, 6410 Fannin St., Suite 830, Houston, TX 77030, USA. robert.amato@uth.tmc.edu
authors.forename: Robert
authors.initials: R
authors.lastname: Amato
authors.forename: Mika
authors.initials: M
authors.lastname: Stepankiw
authors.forename: Patricia
authors.initials: P
authors.lastname: Gonzales
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000813:Anilides / Q000008:administration & dosage / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D018572:Disease-Free Survival; D006801:Humans; D007610:Kallikreins / Q000097:blood; D016729:Leuprolide / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009570:Nitriles / Q000008:administration & dosage / Q000627:therapeutic use; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011878:Radiotherapy; D014105:Tosyl Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D017211:Treatment Failure
chemical_list: D000726:Androgen Antagonists; D000813:Anilides; D018931:Antineoplastic Agents, Hormonal; D009570:Nitriles; D014105:Tosyl Compounds; C053541:bicalutamide; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen; D016729:Leuprolide