title: Phase II study of bortezomib in combination with rituximab, cyclophosphamide and prednisone with or without doxorubicin followed by rituximab maintenance in patients with relapsed or refractory follicular lymphoma.
abstract: This non-comparative phase II study (ClinicalTrials.gov: NCT00715208) evaluated bortezomib in place of vincristine in established rituximab-chemotherapy regimens in relapsed/refractory follicular (FL) or marginal zone lymphoma (MZL). Patients were allocated (physician/patient preference) to receive six 21-d cycles of: bortezomib 1·6 mg/m(2) (days 1, 8), rituximab 375 mg/m(2) (day 1), cyclophosphamide 1000 mg/m(2) (day 1) and prednisone 100 mg (days 1-5; VR-CP; 47 FL, 1 MZL patients); or bortezomib, rituximab, prednisone per VR-CP, cyclophosphamide 750 mg/m(2) and doxorubicin 50 mg/m(2) (day 1; VR-CAP; 4 FL, 2 MZL, 1 chronic lymphocytic leukaemia patients). With VR-CP, the response rate was 77%, with a 27% complete response rate. After a median follow-up of 10·9 months, 40% of patients had relapsed/progressed or died. Median duration of response and progression-free survival was 21·9 and 14·9 months, respectively. Common drug-related grade ≥3 adverse events were neutropenia (25%), thrombocytopenia (6%) and lymphopenia (6%). Thirteen (27%) patients reported peripheral neuropathy (one grade 3). With VR-CAP, one FL patient achieved complete response and three FL and two MZL patients achieved partial responses. Three patients reported drug-related grade 1/2 peripheral neuropathy. Weekly bortezomib and rituximab represents an active, feasible treatment platform in FL. VR-CP was active and well tolerated in patients with relapsed/refractory FL.
authors.affiliation: Mary Babb Randolph Cancer Center, West Virginia University Robert C Byrd Health Science Center, Morgantown, WV, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Craig
authors.forename: Wahid T
authors.initials: WT
authors.lastname: Hanna
authors.forename: Fernando
authors.initials: F
authors.lastname: Cabanillas
authors.forename: Chien-Shing
authors.initials: CS
authors.lastname: Chen
authors.forename: Dixie-Lee
authors.initials: DL
authors.lastname: Esseltine
authors.forename: Rachel
authors.initials: R
authors.lastname: Neuwirth
authors.forename: Owen A
authors.initials: OA
authors.lastname: O'Connor
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D003520:Cyclophosphamide / Q000008:administration & dosage; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy*; D060046:Maintenance Chemotherapy / Q000379:methods; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D011719:Pyrazines / Q000008:administration & dosage; D012008:Recurrence; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D001897:Boronic Acids; D011719:Pyrazines; D000069283:Rituximab; D000069286:Bortezomib; D003520:Cyclophosphamide; D011241:Prednisone
keywords: bortezomib; follicular lymphoma; marginal zone lymphoma; proteasome inhibition; rituximab