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

详细信息    查看全文

• 作者：Craig Reynolds (12) Craig.Reynolds@USOncology.com
  Nicholas Di Bella (13)
  Roger M. Lyons (14)
  William Hyman (15)
  Donald A. Richards (15)
  Gerald J. Robbins (16)
  Mark Vellek (17)
  Kristi A. Boehm (1)
  Feng Zhan (1)
  Lina Asmar (1)
• 关键词：Chemotherapy &#8211 ; Community ; based &#8211 ; Comparative &#8211 ; Infection &#8211 ; Leukemia
• 刊名：Investigational New Drugs
• 出版年：2012
• 出版时间：June 2012
• 年：2012
• 卷：30
• 期：3
• 页码：1232-1240
• 全文大小：159.7 KB
• 参考文献：1. Keating MJ, Kantarjian H, O’Brien S, Koller C, Talpaz M, Schachner J et al (1991) Fludarabine: a new agent with marked cytoreductive activity in untreated chronic lymphocytic leukemia. J Clin Oncol 9(1):44–49
  2. Rai KR, Peterson BL, Appelbaum FR, Kolitz J, Elias L, Shepherd L et al (2000) Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med 343(24):1750–1757
  3. Rai KR, Peterson BL, Appelbaum FR, Tallman MS, Belch A, Morrison VA, et al (2000) Long-term survival analysis of the North American Intergroup Study C9011 comparing fludarabine (F) and chlorambucil (C) in previously untreated patients with chronic lymphocytic leukemia (CLL). Blood (ASH Annual Meeting Abstracts) 114:536
  4. O’Brien SM, Kantarjian H, Thomas DA, Giles FJ, Freireich EJ, Cortes J et al (2001) Rituximab dose-escalation trial in chronic lymphocytic leukemia. J Clin Oncol 19(8):2165–2170
  5. Huhn D, von Schilling C, Wilhelm M, Ho AD, Hallek M, Kuse R et al (2001) Rituximab therapy of patients with B-cell chronic lymphocytic leukemia. Blood 98(5):1326–1331
  6. Byrd JC, Rai K, Peterson BL, Appelbaum FR, Morrison VA, Kolitz JE et al (2005) 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. Blood 105(1):49–53
  7. Wierda W, O’Brien S, Wen S, Faderl S, Garcia-Manero G, Thomas D et al (2005) Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab for relapsed and refractory chronic lymphocytic leukemia. J Clin Oncol 23(18):4070–4078
  8. Keating MJ, O’Brien S, Albitar M, Lerner S, Plunkett W, Giles F et al (2005) Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia. J Clin Oncol 23(18):4079–4088
  9. Tam CS, O’Brien S, Wierda W, Kantarjian H, Wen S, Do KA et al (2008) Long-term results of the fludarabine, cyclophosphamide, and rituximab regimen as initial therapy of chronic lymphocytic leukemia. Blood 112(4):975–980
  10. Dillman RO, Mick R, McIntyre OR (1998) Pentostatin in chronic lymphocytic leukemia: a phase II trial of Cancer and Leukemia group B. J Clin Oncol 7(4):433–438
  11. Ho AD, Thaler J, Stryckmans P, Coiffier B, Luciani M, Sonneveld P et al (1990) Pentostatin in refractory chronic lymphocytic leukemia: a phase II trial of the European Organization for Research and Treatment of Cancer. Natl Cancer Inst 82(17):1416–1420
  12. Weiss MA, Maslak PG, Jurcic JG, Scheinberg DA, Aliff TB, Lamanna N et al (2003) Pentostatin and cyclophosphamide: an effective new regimen in previously treated patients with chronic lymphocytic leukemia. J Clin Oncol 21(7):1278–1284
  13. Kay NE, Geyer SM, Call TG, Shanafelt TD, Zent CS, Jelinek DF et al (2007) Combination chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab shows significant clinical activity with low accompanying toxicity in previously untreated B chronic lymphocytic leukemia. Blood 109(2):405–411
  14. Shanafelt TD, Lin T, Geyer SM, Zent CS, Leung N, Kabat B et al (2007) Pentostatin, cyclophosphamide, and rituximab regimen in older patients with chronic lymphocytic leukemia. Cancer 109(11):2291–2298
  15. Cheson BD, Bennett JM, Grever M, Kay N, Keating MJ, O’Brien S et al (1996) National Cancer Institute—sponsored working group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood 12:4990–4997
  16. National Cancer Institute’s Cancer Therapy Evaluation Program (NCI CTEP) Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0. URL: http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf (accessed August 8, 2009)
  17. Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. JASA 53:457–481
• 作者单位：1. US Oncology Research, LLC., The Woodlands, TX, USA2. Ocala Oncology, 433 SW 10th Street, Ocala, FL 34474, USA3. Rocky Mountain Cancer Centers, Aurora, CO, USA4. Cancer Care Centers of South Texas, San Antonio, TX, USA5. Texas Oncology, Tyler, TX, USA6. Florida Cancer Institute, New Port Richey, FL, USA7. Missouri Cancer Associates, Columbia, MO, USA
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  Pharmacology and Toxicology
  
• 出版者：Springer Netherlands
• ISSN：1573-0646

文摘

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/m2 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.