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

Research output: Contribution to journalArticle

39 Scopus citations

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). 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
Volume30
Issue number3
DOIs
StatePublished - Jun 1 2012
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

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