title: Phase I trial of bortezomib in combination with rituximab-HyperCVAD alternating with rituximab, methotrexate and cytarabine for untreated aggressive mantle cell lymphoma.
abstract: Mantle cell lymphoma (MCL) outcomes have improved over the last two decades; however, late relapses occur. Bortezomib has shown single agent activity of 33% in relapsed MCL and has an additive/synergistic effect in vitro when combined with drugs currently used to treat MCL. We hypothesized that a combination of bortezomib with current intense non-transplant chemoimmunotherapy might prevent late relapses. The toxicity of bortezomib when combined with methotrexate and cytarabine is unknown. Patients aged 18-79 years with untreated aggressive MCL were treated with R-HyperCVAD (rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone) alternating with rituximab-methotrexate/cytarabine (R-M/A). Bortezomib was added to the R-Hyper-CVAD combination as a fixed dose of 1·3 mg/m(2) IV on days 2 and 5 and was added to the R-M/A regimen after rituximab, in increasing doses of 0·7, 1, and 1·3 mg/m(2) in cohorts of three patients. Twenty patients were assessed for toxicity of the regimen. The principal toxicity was haematological and did not differ from that observed with a similar regimen without the bortezomib. In particular, there was no pulmonary or neurological dose-limiting toxicity, showing that bortezomib can be safely combined with R-HyperCVAD and R-M/A.
authors.affiliation: Department of Lymphoma/Myeloma, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd. #429, Houston, TX 77030, USA. jromague@mdanderson.org
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Romaguera
authors.forename: Luis E
authors.initials: LE
authors.lastname: Fayad
authors.forename: Peter
authors.initials: P
authors.lastname: McLaughlin
authors.forename: Barbara
authors.initials: B
authors.lastname: Pro
authors.forename: Alma
authors.initials: A
authors.lastname: Rodriguez
authors.forename: Michael
authors.initials: M
authors.lastname: Wang
authors.forename: Pamela
authors.initials: P
authors.lastname: Weaver
authors.forename: Kimberly
authors.initials: K
authors.lastname: Hartig
authors.forename: Larry W
authors.initials: LW
authors.lastname: Kwak
authors.forename: Tatyana
authors.initials: T
authors.lastname: Feldman
authors.forename: Judy
authors.initials: J
authors.lastname: Smith
authors.forename: Peggy
authors.initials: P
authors.lastname: Ford
authors.forename: Stuart
authors.initials: S
authors.lastname: Goldberg
authors.forename: Andrew
authors.initials: A
authors.lastname: Pecora
authors.forename: Andre
authors.initials: A
authors.lastname: Goy
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / 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; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects; D000069283:Rituximab; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D001897:Boronic Acids; D011719:Pyrazines; D003561:Cytarabine; D000069283:Rituximab; D014750:Vincristine; D000069286:Bortezomib; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D008727:Methotrexate