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).

BACKGROUND: 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.
METHODS: 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/m(2) in Arm A and 1.3 mg/m(2) in Arm B. For the next patients (Step 2), doses were increased to 1.3 mg/m(2) and 1.6 mg/m(2) in Arms A and B, respectively. The primary endpoint was the rate of complete response (CR) and unconfirmed CR (CR/CRu) after 6 cycles.
RESULTS: 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.
CONCLUSIONS: 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. 2009 American Cancer Society.

RCT Entities:   Population Interventions Outcomes