Literature DB >> 21922186

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

Craig Reynolds1, Nicholas Di Bella, Roger M Lyons, William Hyman, Donald A Richards, Gerald J Robbins, Mark Vellek, Kristi A Boehm, Feng Zhan, Lina Asmar.   

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/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.

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Year:  2011        PMID: 21922186     DOI: 10.1007/s10637-011-9737-y

Source DB:  PubMed          Journal:  Invest New Drugs        ISSN: 0167-6997            Impact factor:   3.850


  14 in total

1.  Combination chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab shows significant clinical activity with low accompanying toxicity in previously untreated B chronic lymphocytic leukemia.

Authors:  Neil E Kay; Susan M Geyer; Timothy G Call; Tait D Shanafelt; Clive S Zent; Diane F Jelinek; Renee Tschumper; Nancy D Bone; Gordon W Dewald; Thomas S Lin; Nyla A Heerema; Lisa Smith; Michael R Grever; John C Byrd
Journal:  Blood       Date:  2006-09-28       Impact factor: 22.113

2.  Long-term results of the fludarabine, cyclophosphamide, and rituximab regimen as initial therapy of chronic lymphocytic leukemia.

Authors:  Constantine S Tam; Susan O'Brien; William Wierda; Hagop Kantarjian; Sijin Wen; Kim-Anh Do; Deborah A Thomas; Jorge Cortes; Susan Lerner; Michael J Keating
Journal:  Blood       Date:  2008-04-14       Impact factor: 22.113

3.  Pentostatin in chronic lymphocytic leukemia: a phase II trial of Cancer and Leukemia group B.

Authors:  R O Dillman; R Mick; O R McIntyre
Journal:  J Clin Oncol       Date:  1989-04       Impact factor: 44.544

4.  Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab for relapsed and refractory chronic lymphocytic leukemia.

Authors:  William Wierda; Susan O'Brien; Sijin Wen; Stefan Faderl; Guillermo Garcia-Manero; Deborah Thomas; Kim-Anh Do; Jorge Cortes; Charles Koller; Miloslav Beran; Alessandra Ferrajoli; Francis Giles; Susan Lerner; Maher Albitar; Hagop Kantarjian; Michael Keating
Journal:  J Clin Oncol       Date:  2005-03-14       Impact factor: 44.544

5.  Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia.

Authors:  Michael J Keating; Susan O'Brien; Maher Albitar; Susan Lerner; William Plunkett; Francis Giles; Michael Andreeff; Jorge Cortes; Stefan Faderl; Deborah Thomas; Charles Koller; William Wierda; Michelle A Detry; Alice Lynn; Hagop Kantarjian
Journal:  J Clin Oncol       Date:  2005-03-14       Impact factor: 44.544

6.  Rituximab therapy of patients with B-cell chronic lymphocytic leukemia.

Authors:  D Huhn; C von Schilling; M Wilhelm; A D Ho; M Hallek; R Kuse; W Knauf; U Riedel; A Hinke; S Srock; S Serke; C Peschel; B Emmerich
Journal:  Blood       Date:  2001-09-01       Impact factor: 22.113

7.  Pentostatin in refractory chronic lymphocytic leukemia: a phase II trial of the European Organization for Research and Treatment of Cancer.

Authors:  A D Ho; J Thaler; P Stryckmans; B Coiffier; M Luciani; P Sonneveld; K Lechner; S Rodenhuis; M E Peetermans; F deCataldo
Journal:  J Natl Cancer Inst       Date:  1990-09-05       Impact factor: 13.506

8.  Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia.

Authors:  K R Rai; B L Peterson; F R Appelbaum; J Kolitz; L Elias; L Shepherd; J Hines; G A Threatte; R A Larson; B D Cheson; C A Schiffer
Journal:  N Engl J Med       Date:  2000-12-14       Impact factor: 91.245

9.  Pentostatin and cyclophosphamide: an effective new regimen in previously treated patients with chronic lymphocytic leukemia.

Authors:  Mark A Weiss; Peter G Maslak; Joseph G Jurcic; David A Scheinberg; Timothy B Aliff; Nicole Lamanna; Stanley R Frankel; Steven E Kossman; Denise Horgan
Journal:  J Clin Oncol       Date:  2003-04-01       Impact factor: 44.544

10.  Addition of rituximab to fludarabine may prolong progression-free survival and overall survival in patients with previously untreated chronic lymphocytic leukemia: an updated retrospective comparative analysis of CALGB 9712 and CALGB 9011.

Authors:  John C Byrd; Kanti Rai; Bercedis L Peterson; Frederick R Appelbaum; Vicki A Morrison; Jonathan E Kolitz; Lois Shepherd; John D Hines; Charles A Schiffer; Richard A Larson
Journal:  Blood       Date:  2004-05-11       Impact factor: 22.113

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  15 in total

Review 1.  Role of CD20 monoclonal antibodies in previously untreated chronic lymphocytic leukemia.

Authors:  Sameer A Parikh; William G Wierda
Journal:  Clin Lymphoma Myeloma Leuk       Date:  2010-06

2.  Efficacy and safety of front-line therapy with fludarabine-cyclophosphamide-rituximab regimen for chronic lymphocytic leukemia outside clinical trials: the Israeli CLL Study Group experience.

Authors:  Yair Herishanu; Neta Goldschmidt; Osnat Bairey; Rosa Ruchlemer; Riva Fineman; Naomi Rahimi-Levene; Lev Shvidel; Tamar Tadmor; Aviv Ariel; Andrea Braester; Mika Shapiro; Erel Joffe; Aaron Polliack
Journal:  Haematologica       Date:  2015-02-06       Impact factor: 9.941

Review 3.  Management of chronic lymphocytic leukemia.

Authors:  Paolo Ghia; Michael Hallek
Journal:  Haematologica       Date:  2014-06       Impact factor: 9.941

Review 4.  Chemoimmunotherapy of chronic lymphocytic leukemia.

Authors:  Constantine S Tam; Michael J Keating
Journal:  Nat Rev Clin Oncol       Date:  2010-07-06       Impact factor: 66.675

5.  Pentostatin, Cyclophosphamide and Rituximab (PCR) Regimen.

Authors:  Dominic A Solimando; J Aubrey Waddell
Journal:  Hosp Pharm       Date:  2016-12

6.  Interactions between comorbidity and treatment of chronic lymphocytic leukemia: results of German Chronic Lymphocytic Leukemia Study Group trials.

Authors:  Valentin Goede; Paula Cramer; Raymonde Busch; Manuela Bergmann; Martina Stauch; Georg Hopfinger; Stephan Stilgenbauer; Hartmut Döhner; Anne Westermann; Clemens M Wendtner; Barbara Eichhorst; Michael Hallek
Journal:  Haematologica       Date:  2014-02-28       Impact factor: 9.941

7.  Real-world results of ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia: data from 95 consecutive patients treated in a compassionate use program. A study from the Swedish Chronic Lymphocytic Leukemia Group.

Authors:  Maria Winqvist; Anna Asklid; P O Andersson; Karin Karlsson; Claes Karlsson; Birgitta Lauri; Jeanette Lundin; Mattias Mattsson; Stefan Norin; Anna Sandstedt; Lotta Hansson; Anders Österborg
Journal:  Haematologica       Date:  2016-05-19       Impact factor: 9.941

Review 8.  Chronic Lymphocytic Leukemia and the Side Effects of Therapy: 2017 Review.

Authors:  Asim Ahmad; Clint Daniel Kingsley
Journal:  Mo Med       Date:  2017 May-Jun

Review 9.  Novel CD20 monoclonal antibodies for lymphoma therapy.

Authors:  Shundong Cang; Nikhil Mukhi; Kemeng Wang; Delong Liu
Journal:  J Hematol Oncol       Date:  2012-10-11       Impact factor: 17.388

Review 10.  Update in the management of chronic lymphocytic leukemia.

Authors:  Kami J Maddocks; Thomas S Lin
Journal:  J Hematol Oncol       Date:  2009-07-20       Impact factor: 17.388

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