title: 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.affiliation: Department of Hematology and Oncology, Nagoya Daini Red Cross Hospital, Nagoya, Japan. mi-ogura@naa.att.ne.jp
authors.forename: Michinori
authors.initials: M
authors.lastname: Ogura
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ando
authors.forename: Masafumi
authors.initials: M
authors.lastname: Taniwaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Toshiki
authors.initials: T
authors.lastname: Uchida
authors.forename: Ken
authors.initials: K
authors.lastname: Ohmachi
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Kensei
authors.initials: K
authors.lastname: Tobinai
mesh_terms: D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069461:Bendamustine Hydrochloride; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009588:Nitrogen Mustard Compounds / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D012008:Recurrence; D012074:Remission Induction; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D009588:Nitrogen Mustard Compounds; D000069283:Rituximab; D000069461:Bendamustine Hydrochloride