A Phase III trial of fludarabine, cyclophosphamide, and rituximab vs. pentostatin, cyclophosphamide, and rituximab in B-cell chronic lymphocytic leukemia

Craig Reynolds, Nicholas Di Bella, Roger M. Lyons, William Hyman, Donald A. Richards, Gerald J. Robbins, Mark Vellek, Kristi A. Boehm, Feng Zhan, Lina Asmar

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39 Scopus citations


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). Treatment FCR (F 20 mg/m2 Days 1-5, C 600 mg/m2 Day 1, R 375 mg/m2 Day 1) (28-day cycles) or PCR (P 4 mg/m 2 Day 1, C 600 mg/m2 Day 1, R 375 mg/m2 Day 1) (21-day cycles). Dose 1 of R: 100 mg/m2 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.

Original languageEnglish (US)
Pages (from-to)1232-1240
Number of pages9
JournalInvestigational New Drugs
Issue number3
StatePublished - Jun 1 2012



  • Chemotherapy
  • Community-based
  • Comparative
  • Infection
  • Leukemia

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

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