title: Phase I trial of weekly and twice-weekly bortezomib with rituximab, cyclophosphamide, and prednisone in relapsed or refractory non-Hodgkin lymphoma.
abstract: OBJECTIVE
  To determine the safety and efficacy of substituting weekly or twice-weekly bortezomib for vincristine in the R-CVP (rituximab, cyclophosphamide, vincristine, and prednisone) regimen in patients with relapsed/refractory indolent and mantle cell lymphoma (MCL).
  
  
  METHODS
  Of the 57 patients in this phase I trial, 55 participated in 1 of 2 dosing schedules that included rituximab (375 mg/m(2)) and cyclophosphamide (750 or 1,000 mg/m(2)) administered on day 1 of each 21-day cycle and prednisone (100 mg orally) days 2 to 6. In the once-weekly schedule, bortezomib was administered on days 2 and 8; on the twice-weekly schedule, bortezomib was given on days 2, 5, 9, and 12. Bortezomib and cyclophosphamide were alternately escalated. A separate cohort of 10 patients in the twice-weekly schedule received concurrent pegfilgrastim (PegG) on day 2.
  
  
  RESULTS
  Both schedules of R-CBorP (rituximab, cyclophosphamide, bortezomib, and prednisone) were well tolerated. Most toxicities across all dose levels and cycles were grade 1 or 2. The overall response rates for patients on the weekly (n = 13) and twice-weekly (n = 33) schedules were 46% [23% complete response/complete response unconfirmed (CR/CRu)] and 64% (36% CR/CRu), respectively. Concurrent PegG did not increase hematologic toxicities in this regimen. A randomized phase II study is under way to further compare toxicity and efficacy of the 2 dosing schedules.
  
  
  CONCLUSIONS
  R-CBorP is a safe and effective regimen in patients with relapsed/refractory indolent and MCLs. Most toxicities were grade 1 or 2, and a promising response rate was seen in this phase I study.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York 10065, USA. gerecitj@mskcc.org
authors.forename: John
authors.initials: J
authors.lastname: Gerecitano
authors.forename: Carol
authors.initials: C
authors.lastname: Portlock
authors.forename: Paul
authors.initials: P
authors.lastname: Hamlin
authors.forename: Craig H
authors.initials: CH
authors.lastname: Moskowitz
authors.forename: Ariela
authors.initials: A
authors.lastname: Noy
authors.forename: David
authors.initials: D
authors.lastname: Straus
authors.forename: Philip
authors.initials: P
authors.lastname: Schulman
authors.forename: Otilia
authors.initials: O
authors.lastname: Dumitrescu
authors.forename: Debra
authors.initials: D
authors.lastname: Sarasohn
authors.forename: Jennifer
authors.initials: J
authors.lastname: Pappanicholaou
authors.forename: Alexia
authors.initials: A
authors.lastname: Iasonos
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhang
authors.forename: Qianxing
authors.initials: Q
authors.lastname: Mo
authors.forename: Endri
authors.initials: E
authors.lastname: Horanlli
authors.forename: Celeste N
authors.initials: CN
authors.lastname: Rojas
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Zelenetz
authors.forename: Owen A
authors.initials: OA
authors.lastname: O'Connor
mesh_terms: D000740:Anemia / Q000139:chemically induced; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects; D000069286:Bortezomib; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005334:Fever / Q000139:chemically induced; D005500:Follow-Up Studies; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects; D012008:Recurrence; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D001897:Boronic Acids; D011719:Pyrazines; D000069283:Rituximab; D000069286:Bortezomib; D003520:Cyclophosphamide; D011241:Prednisone