title: Phase I/II trial of vorinostat with rituximab, cyclophosphamide, etoposide and prednisone as palliative treatment for elderly patients with relapsed or refractory diffuse large B-cell lymphoma not eligible for autologous stem cell transplantation.
abstract: The standard treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) in frail elderly patients has not been established. A variation was made on rituximab (R), cyclophosphamide (C), etoposide (E), procarbazine and prednisone (P), substituting vorinostat (V) for procarbazine. Patients ≥aged 60 years with relapsed/refractory DLBCL, not candidates for autologous stem cell transplantation, were treated R-CVEP [R 375 mg/m(2) intravenously (IV), day 1; C 600 mg/m(2) IV days 1, 8: E 70 mg/m(2) IV day 1, 140 mg/m(2) days 2, 3 orally (PO); V (300 vs. 400 mg) PO and P 60 mg/m(2) PO days 1-10] every 28 d for six cycles. Quality of life (QoL) was assessed in addition to response. Thirty patients (median age 76 years, 69-88) were enrolled (one died before treatment). Maximum tolerated dose (MTD) for V was 300 mg. For 23 patients at MTD (six phase I + 17 phase II), two were discontinued for toxicity, one withdrew consent, eight achieved complete response (35%), five achieved partial response (22%) and seven progressed (25%). Median overall survival was 17·5 months. Median progression-free survival was 9·2 months. Nine patients are alive. QoL declined during treatment but improved above baseline for patients who completed treatment. In conclusion, R-CVEP was tolerated at MTD and produced durable responses with improved QoL.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, Division of Hematologic Oncology, Lymphoma Service, New York, NY, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Straus
authors.forename: Paul A
authors.initials: PA
authors.lastname: Hamlin
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Matasar
authors.forename: Maria
authors.initials: M
authors.lastname: Lia Palomba
authors.forename: Pamela R
authors.initials: PR
authors.lastname: Drullinsky
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Zelenetz
authors.forename: John F
authors.initials: JF
authors.lastname: Gerecitano
authors.forename: Ariela
authors.initials: A
authors.lastname: Noy
authors.forename: Audrey M
authors.initials: AM
authors.lastname: Hamilton
authors.forename: Rebecca
authors.initials: R
authors.lastname: Elstrom
authors.forename: Brett
authors.initials: B
authors.lastname: Wegner
authors.forename: Katy
authors.initials: K
authors.lastname: Wortman
authors.forename: David
authors.initials: D
authors.lastname: Cella
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D064592:Autografts; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000009:adverse effects; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D020714:Maximum Tolerated Dose; D010166:Palliative Care; D011239:Prednisolone / Q000008:administration & dosage / Q000009:adverse effects; D012008:Recurrence; D000069283:Rituximab; D033581:Stem Cell Transplantation; D015996:Survival Rate; D000077337:Vorinostat
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D006877:Hydroxamic Acids; D000069283:Rituximab; D000077337:Vorinostat; D005047:Etoposide; D003520:Cyclophosphamide; D011239:Prednisolone
keywords: combination; diffuse large B-cell lymphoma; elderly; relapsed/refractory; vorinostat