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.
© 2010 Blackwell Publishing Ltd.
Publication types
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Clinical Trial, Phase I
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Multicenter Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Age Factors
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Aged
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Antibodies, Monoclonal / administration & dosage
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Antibodies, Monoclonal / adverse effects
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Antibodies, Monoclonal, Murine-Derived
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Antineoplastic Combined Chemotherapy Protocols / administration & dosage
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Antineoplastic Combined Chemotherapy Protocols / adverse effects
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Boronic Acids / administration & dosage
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Boronic Acids / adverse effects
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Bortezomib
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Cyclophosphamide / administration & dosage
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Cyclophosphamide / adverse effects
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Cytarabine / administration & dosage
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Cytarabine / adverse effects
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Dexamethasone / administration & dosage
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Dexamethasone / adverse effects
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Doxorubicin / administration & dosage
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Doxorubicin / adverse effects
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Drug Administration Schedule
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Female
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Humans
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Lymphoma, Mantle-Cell / drug therapy*
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Lymphoma, Mantle-Cell / pathology
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Male
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Methotrexate / administration & dosage
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Methotrexate / adverse effects
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Middle Aged
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Pyrazines / administration & dosage
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Pyrazines / adverse effects
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Rituximab
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Vincristine / administration & dosage
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Vincristine / adverse effects
Substances
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Murine-Derived
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Boronic Acids
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Pyrazines
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Cytarabine
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Rituximab
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Vincristine
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Bortezomib
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Dexamethasone
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Doxorubicin
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Cyclophosphamide
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Methotrexate