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Efficacy and toxicity of 2 schedules of frontline rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone plus bortezomib in patients with B-cell lymphoma†
A randomized phase 2 trial from the French Adult Lymphoma Study Group (GELA)
Article first published online: 10 JUL 2009
Copyright © 2009 American Cancer Society
Volume 115, Issue 19, pages 4540–4546, 1 October 2009
How to Cite
Ribrag, V., Gisselbrecht, C., Haioun, C., Salles, G., Golfier, J.-B., Ertault, M., Ferme, C., Briere, J., Brice, P. and Mounier, N. (2009), Efficacy and toxicity of 2 schedules of frontline rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone plus bortezomib in patients with B-cell lymphoma. Cancer, 115: 4540–4546. doi: 10.1002/cncr.24518
Presented in part at the 43rd Annual Meeting of the American Society of Clinical Oncology, Chicago, Illinois, June 1-5, 2007; and at the 10th International Conference on Malignant Lymphoma, Lugano, Switzerland, June 4-7, 2008
- Issue published online: 17 SEP 2009
- Article first published online: 10 JUL 2009
- Manuscript Received: 30 OCT 2009
- Manuscript Accepted: 11 MAR 2009
- Manuscript Revised: 7 JAN 2009
- B-cell lymphoma;
- phase 2 trial
Bortezomib demonstrated promising activity in lymphomas. The authors conducted a randomized phase 2 trial of frontline rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with the addition of bortezomib in patients with B-cell lymphoma.
Patients were randomized between 2 schedules of bortezomib, Arm A (Days 1, 4, 8, and 11) and Arm B (Days 1 and 8), combined with 6 cycles of R-CHOP. For the first patients (Step 1), bortezomib was given at a dose of 1 mg/m2 in Arm A and 1.3 mg/m2 in Arm B. For the next patients (Step 2), doses were increased to 1.3 mg/m2 and 1.6 mg/m2 in Arms A and B, respectively. The primary endpoint was the rate of complete response (CR) and unconfirmed CR (CR/CRu) after 6 cycles.
Forty-nine patients were included in the study, and 41 patients (84%) achieved a CR/CRu, ie, 18 of 20 patients (90%) in Arm A and 23 of 29 patients (79%) in Arm B. There were 6 partial responses and 2 patients with progressive disease. Neurologic toxicity occurred in 21 patients (43%) and was grade 2 in 11 patients (7 patients in Step 2) and grade 3 in 10 patients (9 patients in Step 2). Other grade 3 and 4 toxicities included constipation (n = 1), infections (n = 3), and cardiac events (n = 2). Grade 3 and 4 thrombocytopenia and leucopenia occurred in 14% and 41% of cycles, respectively.
R-CHOP + bortezomib was an effective regimen and produced an 84% CR rate. However, the dose-limiting neurotoxicity should be kept in mind for further trials with vinca alkaloids or other potentially neurotoxic drugs combination therapies. Cancer 2009. © 2009 American Cancer Society.