Phase III of Study of R-CHOP-21 vs R-CHOP-14 for Untreated Stage III and IV B-cell Non-Hodgkin's Lymphoma: a Report from Iran

  • Payandeh, Mehrdad ;
  • Najafi, Safa ;
  • Shojaiyan, Fateme-Zahra ;
  • Sadeghi, Masoud
  • Published : 2016.04.11


Background: A combination of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is one of the most effective front-line therapies to treat B-cell non-Hodgkin's lymphoma (NHL). The aim of this trial was to evaluate overall survival (OS), progression free survival (PFS) and toxicity of R-CHOP-14 compared to R-CHOP-21 in untreated stage III and IV B-cell NHL patients with Iranian ethnicity. Materials and Methods: In phase III trial, patients with previously untreated stage III and IV indolent and aggressive B-cell NHL were randomly assigned by using a minimization method to receive six to eight cycles of either R-CHOP-21 (administered every 21 days) or R-CHOP-14 (administered every 14 days with granulocyte colony-stimulating factor). Results: A total of 143 patients were randomly enrolled in our study (66 patients in R-CHOP-14 group and 77 patients in R-CHOP-21), between 2011 and 2014. The mean follow-up was 45 months at the time of treatment analysis. The 2-year and 5-year PFS rates for the R-CHOP-14 group were 83.6% vs 73.6% and for R-CHOP-21 group were 75% vs 54%. The 2-year and 5-year OS rates for R-CHOP-14 group were 98% vs 89% and for R-CHOP-21 group were 84.4% vs 67.5%. There was a significant correlation for PFS and OS in the two arms. There was no significant difference between adverse events with the two regimens. Conclusions: In our research improved survival was found with CHOP-14 as compared to CHOP-21. It is possible that drug metabolism in different races/ethnicities may be one important factor.


Non-hodgkin's lymphoma;phase III trial;R-CHOP;overall survival;progression-free survival


  1. Armitage JO (2012). My treatment approach to patients with diffuse large B-cell lymphoma. Mayo Clin Proc, 87, 161-71.
  2. Bernard M, Cartron G, Rachieru P, et al (2005). Long-term outcome of localized high-grade non-Hodgkin's lymphoma treated with high dose CHOP regimen and involved field radiotherapy: results of a GOELAMS study. Haematologica, 90, 802-9.
  3. Cunningham D, Hawkes EA, Jack A, et al (2013). Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet, 381, 1817-26.
  4. Delarue R, Tilly H, Mounier N, et al (2013). Dose-dense rituximab-CHOP compared with standard rituximab-CHOP in elderly patients with diffuse large B-cell lymphoma (the LNH03-6B study): a randomised phase 3 trial. Lancet Onco, 14, 525-33.
  5. Delarue R, Tilly H, Mounier N, et al (2009). R-CHOP14 compared to R-CHOP21 in elderly patients with diffuse large B-cell lymphoma: results of the interim analysis of the LNH03-6B GELA study. Blood, 114, 52.
  6. Gisselbrecht C (2011). Current approaches to the treatment of non-Hodgkin’s lymphoma. Hematol Rep, 28, 3.
  7. Haioun C, Salar A, Pettengell R, et al (2011). Anemia and erythropoiesis-stimulating agent administration in patients with non-Hodgkin lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisolone ${\pm}$ rituximab chemotherapy: results from an observational study. Leuk Lymphoma, 52, 796-803.
  8. Halaas JL, Moskowitz CH, Horwitz S, et al (2005). R-CHOP-14 in patients with diffuse large B-cell lymphoma: feasibility and preliminary efficacy. Leuk Lymphoma, 46, 541-7.
  9. Hiddemann W, Kneba M, Dreyling M, et al (2005). Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: Results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood, 106, 3725-32.
  10. Itoh K, Ohtsu T, Fukuda H, et al (2002). Randomized phase II study of biweekly CHOP and dose-escalated CHOP with prophylactic use of lenograstim (glycosylated G-CSF) in aggressive non-Hodgkin's lymphoma: Japan Clinical Oncology Group Study 9505. Ann Oncol, 13, 1347-55.
  11. Jaffe ES, Harris NL, Stein H, et al (2001). World Health Organisation Classifi cation of Tumours. Pathology and genetics of tumours of haematopoietic and lymphoid tissues. Lyon: IARC Press.
  12. Kikuchi M, Nakasone H, Akahoshi Y, et al (2015). Reduced-dose (two-thirds) R-CHOP chemotherapy for elderly patients with non-Hodgkin lymphoma. J Chemother, 27, 99-105.
  13. Levi I, Feuchtwanger M, Rabinovich A, et al (2013). Clinical and epidemiologic characteristics of non Hodgkin's lymphoma in Bedouins in the south of Israel. Springerplus, 2, 672.
  14. Lin TY, Zhang HY, Huang Y, et al (2005). [Comparison between R-CHOP regimen and CHOP regimen in treating naive diffuse large B-cell lymphoma in China--a multi-center randomized trial]. Ai Zheng, 24, 1421-6.
  15. Ohmachi K, Tobinai K, Kobayashi Y, et al (2011). Phase III trial of CHOP-21 versus CHOP-14 for aggressive non-Hodgkin's lymphoma: final results of the Japan clinical oncology group study, JCOG 9809. Ann Oncol, 22, 1382-91.
  16. Pfreundschuh M, Trumper L, Kloess M, et al (2004). Twoweekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood, 104, 634-41.
  17. Pfreundschuh M, Trumper L, Osterborg A, et al (2006). CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol, 7, 379-91.
  18. Salles G, Seymour JF, Offner F, et al (2011). Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): A phase 3, randomised controlled trial. Lancet, 377, 42-51.
  19. Sawada KI, Sato N, Kohno M, et al (1995). Efficacy of delayed granulocyte colony-stimulating factor after full dose CHOP therapy in non-Hodgkin's lymphoma: a pilot study for a leukocyte count oriented regimen. Leuk Lymphoma, 20, 103-9.
  20. Vidal L, Shpilberg O, Gurion R, et al (2015). CHOP-like-14 compared to CHOP-like-21 for patients with aggressive lymphoma - a meta-analysis of randomized controlled trials. Acta Oncol, 1-8.
  21. Wang M, Burau KD, Fang S, et al (2008). Ethnic variations in diagnosis, treatment, socioeconomic status, and survival in a large population-based cohort of elderly patients with non-Hodgkin lymphoma. Cancer, 113, 3231-41.
  22. Watanabe T, Tobinai K, Shibata T, et al (2011). Phase II/III study of R-CHOP-21 versus R-CHOP-14 for untreated indolent B-cell non-Hodgkin's lymphoma: JCOG 0203 trial. J Clin Oncol, 29, 3990-8.


Supported by : Roche Company