Feasibility and pharmacokinetic study of bendamustine hydrochloride in combination with rituximab in relapsed or refractory aggressive B cell non-Hodgkin's lymphoma.

Abstract

Although bendamustine plus rituximab has demonstrated efficacy in indolent B cell non-Hodgkin's lymphoma (B-NHL), data for this combination in aggressive B-NHL are extremely limited. The present dose-escalation study evaluated the safety, efficacy, and pharmacokinetics of bendamustine hydrochloride in combination with rituximab in patients with relapsed/refractory, CD20-positive, aggressive B-NHL. Patients received rituximab 375 mg/m(2) , i.v., on Day 1 and bendamustine at either 90 (Cohort 1) or 120 mg/m(2) (Cohort 2), i.v., on Days 2 and 3 of a 21-day cycle. The primary endpoint was the proportion of patients experiencing dose-limiting toxicity (DLT). Secondary endpoints were adverse events (AE), the overall response rate (ORR), and pharmacokinetic parameters. Nine patients received rituximab plus bendamustine: three in Cohort 1 and six in Cohort 2. Histologies included diffuse large B cell lymphoma (n = 5), mantle cell lymphoma (n = 2), and transformed lymphoma (n = 2). No DLT was observed at either dose level. Grade 3/4 hematologic AE included lymphocytopenia, leukocytopenia, and neutropenia (n = 9 each; 100%), and thrombocytopenia (n = 2; 22%). No Grade 3/4 gastrointestinal AE were reported. The ORR was 33% (one partial response) in Cohort 1 and 100% (five complete and one partial response) in Cohort 2. The maximum drug concentration and area under the blood concentration-time curve for bendamustine increased dose dependently, with time to maximum blood concentration = 1.0 h in both cohorts; these pharmacokinetic data were similar to those reported previously for single-agent bendamustine in patients with indolent B-NHL. In conclusion, bendamustine 120 mg/m(2) plus rituximab 375 mg/m(2) was feasible and generally well tolerated, with promising efficacy in relapsed or refractory aggressive B-NHL.

• Authors: Michinori Ogura, Kiyoshi Ando, Masafumi Taniwaki, Takashi Watanabe, Toshiki Uchida, Ken Ohmachi, Yosuke Matsumoto, Kensei Tobinai, Japanese Bendamustine Lymphoma Study Group
• Journal: Cancer science (Cancer Sci) Vol. 102 Issue 9 Pg. 1687-92 (Sep 2011) ISSN: 1349-7006 [Electronic] England
• PMID: 21624007 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 Japanese Cancer Association.

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• Nitrogen Mustard Compounds
• Rituximab
• Bendamustine Hydrochloride

Topics

• Aged
• Antibodies, Monoclonal, Murine-Derived (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Bendamustine Hydrochloride
• Drug Administration Schedule
• Feasibility Studies
• Female
• Humans
• Lymphoma, B-Cell (drug therapy, metabolism)
• Male
• Middle Aged
• Nitrogen Mustard Compounds (administration & dosage, adverse effects, pharmacokinetics)
• Recurrence
• Remission Induction
• Rituximab