title: A Phase III trial of fludarabine, cyclophosphamide, and rituximab vs. pentostatin, cyclophosphamide, and rituximab in B-cell chronic lymphocytic leukemia.
abstract: BACKGROUND
  Uncontrolled studies comparing pentostatin (P), cyclophosphamide (C), and rituximab (R) (PCR) to fludarabine plus C+R (FCR) suggest similar efficacy with fewer infectious complications with PCR. We compared FCR and PCR in previously-untreated or minimally-treated B-cell chronic lymphocytic leukemia (CLL).
  
  
  METHODS
  FCR (F 20 mg/m(2) Days 1-5, C 600 mg/m(2) Day 1, R 375 mg/m(2) Day 1) (28-day cycles) or PCR (P 4 mg/m(2) Day 1, C 600 mg/m(2) Day 1, R 375 mg/m(2) Day 1) (21-day cycles). Dose 1 of R: 100 mg/m(2) was given on Day 8 Cycle 1 and the remainder on Day 9; in subsequent cycles the entire dose was given on Day 1.
  
  
  RESULTS
  Ninety-two patients were randomly assigned to each group (N = 184). Groups were balanced; ~20% had received prior chemotherapy. The infection rate (FCR/PCR) was 31%/36%, the infective event rate was 38%/45%; 30 (35%)/37 (44%) patients were hospitalized; total hospitalization days was 271/404. 12 (14%)/6 (7%) patients achieved complete remissions (CR); the overall response rate (ORR) including CR+nodular PR (nPR)+PR was 59%/49%. Grade 3-4 treatment related AEs: neutropenia (69%/57%), leukopenia (34%/17%), thrombocytopenia (13%/6%). Grade 3-4 infections: febrile neutropenia (8%/6%), fever (2%/6%), infection (1%/3%), urinary tract infection (1%/0%), pneumonia (3%/1%), and sepsis (1%/2%); 5 deaths (1 FCR/4 PCR) were treatment-related.
  
  
  CONCLUSIONS
  PCR and FCR have significant activity in CLL and can be given safely in the community setting despite significant toxicity. ORRs were lower than expected; the CR rate was higher (NS) with FCR. This trial did not demonstrate a lower infection rate with PCR.
authors.affiliation: US Oncology Research, LLC., The Woodlands, TX, USA. Craig.Reynolds@USOncology.com
authors.forename: Craig
authors.initials: C
authors.lastname: Reynolds
authors.forename: Nicholas
authors.initials: N
authors.lastname: Di Bella
authors.forename: Roger M
authors.initials: RM
authors.lastname: Lyons
authors.forename: William
authors.initials: W
authors.lastname: Hyman
authors.forename: Donald A
authors.initials: DA
authors.lastname: Richards
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Robbins
authors.forename: Mark
authors.initials: M
authors.lastname: Vellek
authors.forename: Kristi A
authors.initials: KA
authors.lastname: Boehm
authors.forename: Feng
authors.initials: F
authors.lastname: Zhan
authors.forename: Lina
authors.initials: L
authors.lastname: Asmar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015649:Pentostatin / Q000008:administration & dosage / Q000009:adverse effects; D000069283:Rituximab; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D015649:Pentostatin; D000069283:Rituximab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine