title: Phase II/III study of R-CHOP-21 versus R-CHOP-14 for untreated indolent B-cell non-Hodgkin's lymphoma: JCOG 0203 trial.
abstract: OBJECTIVE
  Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is one of the most effective front-line therapies to treat indolent B-cell lymphoma. Granulocyte colony-stimulating factor (G-CSF), which potentiates antibody-dependent rituximab cytotoxicity, is used to shorten CHOP intervals. To improve progression-free survival (PFS) in patients treated with R-CHOP as the primary end point, we conducted a phase III study.
  
  
  METHODS
  Patients with untreated stages III to IV indolent B-cell lymphoma were randomly assigned to six cycles of R-CHOP every 3 weeks (R-CHOP-21) or every 2 weeks (R-CHOP-14) with G-CSF. Maintenance rituximab was not allowed.
  
  
  RESULTS
  Three hundred patients were enrolled. At the median follow-up time of 5.2 years, there was no significant difference in PFS between arms for the 299 eligible patients; the median was 3.7 (R-CHOP-21) v 4.7 (R-CHOP-14) years, 57% v 58% at 3 years, and 41% v 43% at 6 years, respectively (hazard ratio [HR], 0.92; 95% CI, 0.68 to 1.25; one-sided P = .30). The median overall survival (OS) time was not reached in either arm, and there was no significant difference (6-year OS: 87% [R-CHOP-21] v 88% [R-CHOP-14]; HR, 1.15; 95% CI, 0.57 to 2.30; one-sided P = .65). Although grade 4 neutropenia and grade 3 infections were more frequent in the R-CHOP-21 group, R-CHOP was feasible in both arms.
  
  
  CONCLUSIONS
  The R-CHOP dose-dense strategy failed to improve PFS of patients with untreated indolent B-cell lymphoma. Further improvement of first-line treatment or investigations on postremission therapy following R-CHOP should be explored.
authors.affiliation: Hematology and Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan. takawata@ncc.go.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Kensei
authors.initials: K
authors.lastname: Tobinai
authors.forename: Taro
authors.initials: T
authors.lastname: Shibata
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Tsukasaki
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morishima
authors.forename: Nobuo
authors.initials: N
authors.lastname: Maseki
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Takayo
authors.initials: T
authors.lastname: Suzuki
authors.forename: Motoko
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ando
authors.forename: Michinori
authors.initials: M
authors.lastname: Ogura
authors.forename: Masafumi
authors.initials: M
authors.lastname: Taniwaki
authors.forename: Naokuni
authors.initials: N
authors.lastname: Uike
authors.forename: Kengo
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Nawano
authors.forename: Takashi
authors.initials: T
authors.lastname: Terauchi
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Hotta
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D000069283:Rituximab; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D016179:Granulocyte Colony-Stimulating Factor; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone