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

PURPOSE:

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.

PATIENTS AND 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.

CONCLUSION:

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: Takashi Watanabe, Kensei Tobinai, Taro Shibata, Kunihiro Tsukasaki, Yasuo Morishima, Nobuo Maseki, Tomohiro Kinoshita, Takayo Suzuki, Motoko Yamaguchi, Kiyoshi Ando, Michinori Ogura, Masafumi Taniwaki, Naokuni Uike, Kengo Takeuchi, Shigeru Nawano, Takashi Terauchi, Tomomitsu Hotta
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 29 Issue 30 Pg. 3990-8 (Oct 20 2011) ISSN: 1527-7755 [Electronic] United States
• PMID: 21931035 (Publication Type: Clinical Trial, Phase II, Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• Granulocyte Colony-Stimulating Factor
• Rituximab
• Vincristine
• Doxorubicin
• Cyclophosphamide
• Prednisone

Topics

• Adult
• Aged
• Antibodies, Monoclonal, Murine-Derived (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Cyclophosphamide (administration & dosage, adverse effects)
• Disease-Free Survival
• Doxorubicin (administration & dosage, adverse effects)
• Drug Administration Schedule
• Granulocyte Colony-Stimulating Factor (administration & dosage)
• Humans
• Lymphoma, B-Cell (drug therapy, pathology)
• Middle Aged
• Neoplasm Staging
• Prednisone (administration & dosage, adverse effects)
• Rituximab
• Survival Rate
• Vincristine (administration & dosage, adverse effects)