Phase I trial of bortezomib in combination with rituximab-HyperCVAD alternating with rituximab, methotrexate and cytarabine for untreated aggressive mantle cell lymphoma.
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.
Romaguera
Jorge E
JE
Department of Lymphoma/Myeloma, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd. #429, Houston, TX 77030, USA. jromague@mdanderson.org
Fayad
Luis E
LE
McLaughlin
Peter
P
Pro
Barbara
B
Rodriguez
Alma
A
Wang
Michael
M
Weaver
Pamela
P
Hartig
Kimberly
K
Kwak
Larry W
LW
Feldman
Tatyana
T
Smith
Judy
J
Ford
Peggy
P
Goldberg
Stuart
S
Pecora
Andrew
A
Goy
Andre
A
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
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