title: 5-year survival in patients with relapsed or refractory chronic lymphocytic leukemia in a randomized, phase III trial of fludarabine plus cyclophosphamide with or without oblimersen.
abstract: OBJECTIVE
  A randomized trial of oblimersen plus fludarabine/cyclophosphamide (OBL-FC; n = 120) versus FC (n = 121) was conducted in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). The primary end point was met: the complete response (CR) rate, defined as complete or nodular partial response, was significantly greater with OBL-FC than with FC (17% v 7%; P = .025). Among patients with CR, response duration was significantly longer with OBL-FC than with FC (median not reached; > 36 months v 22 months; P = .03). Maximum benefit with OBL-FC, including a four-fold increase in CR rate and a survival benefit with 3 years of follow-up (hazard ratio, 0.53; P = .05), was observed in patients with fludarabine-sensitive disease. We evaluated long-term survival and poststudy CLL therapy among all randomly assigned patients.
  
  
  METHODS
  Poststudy CLL treatment information was collected. Patients were observed for survival for up to 5 years from the date of random assignment.
  
  
  RESULTS
  Poststudy CLL treatment was balanced between arms. Intent-to-treat analysis of 5-year survival showed no significant between-treatment difference (hazard ratio, 0.87; P = .34). Among the greater than 40% of patients with complete or partial remission, a significant 5-year survival benefit was observed with OBL-FC (hazard ratio, 0.60; P = .038). Among patients with fludarabine-sensitive disease who had previously demonstrated maximum benefit with OBL-FC, the previously observed survival benefit improved: a 50% reduction in the risk of death was observed (P = .004).
  
  
  CONCLUSIONS
  In relapsed/refractory CLL, OBL combined with FC offers patients who achieve complete or partial remission, as well as those who have fludarabine-sensitive disease, a significant survival benefit.
authors.affiliation: Division of Hematology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. sobrien@mdanderson.org
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Joseph O
authors.initials: JO
authors.lastname: Moore
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Boyd
authors.forename: Loree M
authors.initials: LM
authors.lastname: Larratt
authors.forename: Aleksander B
authors.initials: AB
authors.lastname: Skotnicki
authors.forename: Benjamin
authors.initials: B
authors.lastname: Koziner
authors.forename: Asher A
authors.initials: AA
authors.lastname: Chanan-Khan
authors.forename: John F
authors.initials: JF
authors.lastname: Seymour
authors.forename: John
authors.initials: J
authors.lastname: Gribben
authors.forename: Loretta M
authors.initials: LM
authors.lastname: Itri
authors.forename: Kanti R
authors.initials: KR
authors.lastname: Rai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality*; D013873:Thionucleotides / Q000008:administration & dosage; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D013873:Thionucleotides; C408162:oblimersen; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine