Sequence-dependent synergy of the proteasome inhibitor bortezomib and cytarabine in mantle cell lymphoma.
Single-agent bortezomib, a potent, selective and reversible inhibitor of the 26S proteasome, has demonstrated clinical efficacy in relapsed and refractory mantle cell lymphoma (MCL). Objective response is achieved in up to 45% of the patients; however, complete remission rates are low and duration of response proved to be short. These limitations may be overcome by combining proteasome inhibition with conventional chemotherapy. Here we present two case reports and in vitro data suggesting synergistic efficacy of bortezomib combined with cytarabine in MCL. Interestingly, efficacy in vitro correlated with sequence of treatment, indicating that pretreatment with cytarabine, followed by proteasome inhibition, may be the preferred approach.
Weigert
O
O
Department of Internal Medicine III, University of Munich, University Hospital Grosshadern, Munich, Germany.
Pastore
A
A
Rieken
M
M
Lang
N
N
Hiddemann
W
W
Dreyling
M
M
D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001897:Boronic Acids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000069286:Bortezomib; D045744:Cell Line, Tumor / Q000187:drug effects; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005260:Female; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D011241:Prednisone / Q000008:administration & dosage; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects*; D011719:Pyrazines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016499:Radioimmunotherapy; D012008:Recurrence; D012074:Remission Induction; D000069283:Rituximab; D016879:Salvage Therapy; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014750:Vincristine / Q000008:administration & dosage; D015021:Yttrium Radioisotopes / Q000008:administration & dosage / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D001897:Boronic Acids; D011480:Protease Inhibitors; D011719:Pyrazines; D015021:Yttrium Radioisotopes; D003561:Cytarabine; D000069283:Rituximab; C422802:ibritumomab tiuxetan; D014750:Vincristine; D000069286:Bortezomib; D004317:Doxorubicin; D003520:Cyclophosphamide; D008942:Mitoxantrone; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D014740:Vidarabine; D011241:Prednisone