title: Prospective phase II study of rituximab with alternating cycles of hyper-CVAD and high-dose methotrexate with cytarabine for young patients with high-risk diffuse large B-cell lymphoma.
abstract: We conducted a prospective randomized phase II study to evaluate two chemotherapy regimens: (i) rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone (R-HCVAD) alternating with rituximab, high-dose methotrexate, and cytarabine (R-MA) and (ii) rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) in diffuse large B-cell lymphoma (DLBCL). This study randomized patients aged ≤60 years with DLBCL and an age-adjusted international prognostic index ≥2 to R-HCVAD/R-MA or R-CHOP based on a Bayesian adaptive algorithm. Interim analysis of the first 26 eligible patients showed that the complete response rate (CRR) was higher with R-HCVAD/R-MA than R-CHOP (P = 0·03); thus, R-CHOP arm was closed. In the final analysis, 49 and 10 eligible patients were treated in R-HCVAD/R-MA and R-CHOP arms respectively; CRR were 82% and 60% respectively (P = 0·13); 3-year progression-free survival (PFS) rates were 75·7% and 77·8% respectively (P = 0·53). In the R-HCVAD/R-MA arm, 3-year PFS rates in patients aged 46-60 years and ≤45 years were 70·3% and 87·1% respectively (P = 0·13), and the treatment-associated early mortality rate in patients >45 years was 12%. In conclusion, R-HCVAD/R-MA is associated with excellent outcome in patients ≤45 years old. However, in patients >45 years old, R-HCVAD/R-MA is associated with unacceptable mortality rates.
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Oki
authors.forename: Jason R
authors.initials: JR
authors.lastname: Westin
authors.forename: Francisco
authors.initials: F
authors.lastname: Vega
authors.forename: Hubert
authors.initials: H
authors.lastname: Chuang
authors.forename: Nathan
authors.initials: N
authors.lastname: Fowler
authors.forename: Sattva
authors.initials: S
authors.lastname: Neelapu
authors.forename: Fredrick B
authors.initials: FB
authors.lastname: Hagemeister
authors.forename: Peter
authors.initials: P
authors.lastname: McLaughlin
authors.forename: Larry W
authors.initials: LW
authors.lastname: Kwak
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Romaguera
authors.forename: Michelle
authors.initials: M
authors.lastname: Fanale
authors.forename: Anas
authors.initials: A
authors.lastname: Younes
authors.forename: Maria Alma
authors.initials: MA
authors.lastname: Rodriguez
authors.forename: Robert Z
authors.initials: RZ
authors.lastname: Orlowski
authors.forename: Michael
authors.initials: M
authors.lastname: Wang
authors.forename: Souzanne T
authors.initials: ST
authors.lastname: Ouzounian
authors.forename: Felipe
authors.initials: F
authors.lastname: Samaniego
authors.forename: Luis
authors.initials: L
authors.lastname: Fayad
mesh_terms: D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001499:Bayes Theorem; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D011446:Prospective Studies; D012306:Risk; D000069283:Rituximab; D013927:Thrombosis / Q000139:chemically induced; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D003561:Cytarabine; D000069283:Rituximab; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone; D008727:Methotrexate
keywords: clinical trial; diffuse large B-cell lymphoma; intensive chemotherapy