title: Randomized phase II trial of docetaxel plus prednisone in combination with placebo or AT-101, an oral small molecule Bcl-2 family antagonist, as first-line therapy for metastatic castration-resistant prostate cancer.
abstract: BACKGROUND
  AT-101 (A), a small molecule oral inhibitor of the Bcl-2 family, has activity alone and in combination with docetaxel (Taxotere) and prednisone (DP) in metastatic castration-resistant prostate cancer (mCRPC). A randomized, double-blind, placebo-controlled phase II trial compared DP combined with either AT-101 (A) or placebo in chemonaive mCRPC.
  
  
  METHODS
  Men with progressive mCRPC despite androgen deprivation were eligible and randomized 1:1. Patients received docetaxel (75 mg/m2 day 1) and prednisone 5 mg orally twice daily every 21 days with either AT-101 (40 mg) or placebo twice daily orally on days 1-3. The primary end point was overall survival (OS).
  
  
  RESULTS
  Two hundred and twenty-one patients were randomly assigned. Median OS for AT-101 plus docetaxel-prednisone (ADP) and placebo-DP was 18.1 versus 17.8 months [hazard ratio (HR) 1.07, 95% confidence interval 0.72-1.55, P=0.63]. Secondary end points were also not statistically different. Grade 3/4 toxic effects for ADP versus placebo-DP were cardiac events (5% versus 2%), lymphopenia (23% versus 16%), neutropenia (47% versus 40%), ileus (2% versus 0%) and pulmonary embolism (6% versus 2%). In a subgroup of high-risk mCRPC (n=34), outcomes appeared to favor ADP (median OS 19 versus 14 months).
  
  
  CONCLUSIONS
  AT-101 was tolerable but did not extend OS when combined with DP in mCRPC; a potential benefit was observed in high-risk patients.
authors: Texas Oncology and US Oncology Research, Houston, TX, USA. guru.sonpavde@usoncology.com
authors: G
authors: G
authors: Sonpavde
authors: V
authors: V
authors: Matveev
authors: J M
authors: JM
authors: Burke
authors: J R
authors: JR
authors: Caton
authors: M T
authors: MT
authors: Fleming
authors: T E
authors: TE
authors: Hutson
authors: M D
authors: MD
authors: Galsky
authors: W R
authors: WR
authors: Berry
authors: P
authors: P
authors: Karlov
authors: J T
authors: JT
authors: Holmlund
authors: B A
authors: BA
authors: Wood
authors: M
authors: M
authors: Brookes
authors: L
authors: L
authors: Leopold
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000077143:Docetaxel; D006072:Gossypol / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating; D009919:Orchiectomy; D010919:Placebos / Q000008:administration & dosage; D011241:Prednisone / Q000008:administration & dosage; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D010919:Placebos; D019253:Proto-Oncogene Proteins c-bcl-2; D043823:Taxoids; D000077143:Docetaxel; D006072:Gossypol; C028178:gossypol acetic acid; D011241:Prednisone