title: A phase II study of bortezomib added to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone in patients with previously untreated indolent non-Hodgkin's lymphoma.
abstract: Bortezomib-containing combinations are active in non-Hodgkin lymphoma (NHL) although peripheral neuropathy can limit their dose intensity. Based on our phase I findings, we conducted a phase II trial of bortezomib in combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) with a modified dose of vincristine. Patients with untreated indolent NHL received bortezomib (1·6 mg/m(2) ) on days 1 and 8 of a 21-day cycle for up to 8 cycles and R-CHOP with a 1·5 mg cap of vincristine. Patients achieving a complete response (CR) received maintenance rituximab, and remaining patients received maintenance rituximab and bortezomib. The primary endpoint was CR rate; secondary survival analyses were evaluated using the Kaplan-Meier method. Among 29 eligible patients, NHL morphologies included follicular (n = 20), marginal zone (n = 5) and small lymphocytic lymphoma (n = 4). Nineteen patients had CR (66%) and 10 had partial response (34%), yielding a 100% overall response rate. With a median follow-up of 48·7 months, the 4-year progression-free and overall survivals were 83% and 93%. Twenty-two patients experienced peripheral neuropathy of any grade, and two had grade 3 neuropathy. The combination of bortezomib with R-CHOP is effective for indolent NHL, and we plan to evaluate therapies incorporating novel proteasome inhibitors in future studies in NHL.
authors.affiliation: Hematology and Medical Oncology, Emory University, Atlanta, GA, USA.|Winship Cancer Institute, Emory University, Atlanta, GA, USA.
authors.forename: Jonathon B
authors.initials: JB
authors.lastname: Cohen
authors.affiliation: Biostatistics and Bioinformatics, Emory University, Atlanta, GA, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Switchenko
authors.affiliation: Hematology and Medical Oncology, Emory University, Atlanta, GA, USA.
authors.forename: Jean L
authors.initials: JL
authors.lastname: Koff
authors.affiliation: Hematology and Medical Oncology, Emory University, Atlanta, GA, USA.|Winship Cancer Institute, Emory University, Atlanta, GA, USA.
authors.forename: Rajni
authors.initials: R
authors.lastname: Sinha
authors.affiliation: Hematology and Medical Oncology, Emory University, Atlanta, GA, USA.|Winship Cancer Institute, Emory University, Atlanta, GA, USA.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Kaufman
authors.affiliation: Hematology and Medical Oncology, Emory University, Atlanta, GA, USA.|Winship Cancer Institute, Emory University, Atlanta, GA, USA.
authors.forename: H Jean
authors.initials: HJ
authors.lastname: Khoury
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA, USA.
authors.forename: Nassoma
authors.initials: N
authors.lastname: Bumpers
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Colbert
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Hutchison-Rzepka
authors.affiliation: Hematology and Medical Oncology, Emory University, Atlanta, GA, USA.
authors.forename: Loretta J
authors.initials: LJ
authors.lastname: Nastoupil
authors.affiliation: Hematology and Medical Oncology, Emory University, Atlanta, GA, USA.|Winship Cancer Institute, Emory University, Atlanta, GA, USA.
authors.forename: Leonard T
authors.initials: LT
authors.lastname: Heffner
authors.affiliation: Hematology and Medical Oncology, Emory University, Atlanta, GA, USA.|Winship Cancer Institute, Emory University, Atlanta, GA, USA.
authors.forename: Amelia A
authors.initials: AA
authors.lastname: Langston
authors.affiliation: Hematology and Medical Oncology, Emory University, Atlanta, GA, USA.|Winship Cancer Institute, Emory University, Atlanta, GA, USA.
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: Lechowicz
authors.affiliation: Hematology and Medical Oncology, Emory University, Atlanta, GA, USA.|Winship Cancer Institute, Emory University, Atlanta, GA, USA.
authors.forename: Sagar
authors.initials: S
authors.lastname: Lonial
authors.affiliation: Hematology and Medical Oncology, Emory University, Atlanta, GA, USA.|Winship Cancer Institute, Emory University, Atlanta, GA, USA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Flowers
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib / Q000009:adverse effects / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D053208:Kaplan-Meier Estimate; D008224:Lymphoma, Follicular / Q000188:drug therapy; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D011241:Prednisone / Q000008:administration & dosage; D000069283:Rituximab / Q000009:adverse effects / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D000069283:Rituximab; D014750:Vincristine; D000069286:Bortezomib; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone
keywords: bortezomib; follicular lymphoma; indolent lymphoma; neuropathy; non-Hodgkin lymphoma