title: A phase II study of cyclophosphamide, etoposide, vincristine and prednisone (CEOP) Alternating with Pralatrexate (P) as front line therapy for patients with peripheral T-cell lymphoma (PTCL): final results from the T- cell consortium trial.
abstract: Peripheral T-cell lymphomas (PTCL) have suboptimal outcomes using conventional CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy. The anti-folate pralatrexate, the first drug approved for patients with relapsed/refractory PTCL, provided a rationale to incorporate it into the front-line setting. This phase 2 study evaluated a novel front-line combination whereby cyclophosphamide, etoposide, vincristine and prednisone (CEOP) alternated with pralatrexate (CEOP-P) in PTCL. Patients achieving a complete or partial remission (CR/PR) were eligible for consolidative stem cell transplantation (SCT) after 4 cycles. Thirty-three stage II-IV PTCL patients were treated: 21 PTCL-not otherwise specified (64%), 8 angioimmunoblastic T cell lymphoma (24%) and 4 anaplastic large cell lymphoma (12%). The majority (61%) had stage IV disease and 46% were International Prognostic Index high/intermediate or high risk. Grade 3-4 toxicities included anaemia (27%), thrombocytopenia (12%), febrile neutropenia (18%), mucositis (18%), sepsis (15%), increased creatinine (12%) and liver transaminases (12%). Seventeen patients (52%) achieved a CR. The 2-year progression-free survival and overall survival, were 39% (95% confidence interval 21-57) and 60% (95% confidence interval 39-76), respectively. Fifteen patients (45%) (12 CR) received SCT and all remained in CR at a median follow-up of 21·5 months. CEOP-P did not improve outcomes compared to historical data using CHOP. Defining optimal front line therapy in PTCL continues to be a challenge and an unmet need.
authors.affiliation: Medical Oncology, Stanford Cancer Institute, Stanford, CA, USA.
authors.forename: Ranjana H
authors.initials: RH
authors.lastname: Advani
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Ansell
authors.affiliation: Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Lechowicz
authors.affiliation: Medicine-Oncology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Anne W
authors.initials: AW
authors.lastname: Beaven
authors.affiliation: Division of Hematology/Oncology, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Fausto
authors.initials: F
authors.lastname: Loberiza
authors.affiliation: Division of Medical Oncology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Carson
authors.affiliation: Division of Hematology/Oncology, Tufts Medical Center, Boston, MA, USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Evens
authors.affiliation: Yale University Cancer Center, New Haven, CT, USA.
authors.forename: Francine
authors.initials: F
authors.lastname: Foss
authors.affiliation: Hematology/Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Horwitz
authors.affiliation: Medical Oncology, Jefferson University Hospital, Philadelphia, PA, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Pro
authors.affiliation: Hematology/Oncology, UCLA Geffen School of Medicine, Los Angeles, CA, USA.
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Pinter-Brown
authors.affiliation: Center for Advanced Medicine, University of Chicago, Chicago, IL, USA.
authors.forename: Sonali M
authors.initials: SM
authors.lastname: Smith
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Andrei R
authors.initials: AR
authors.lastname: Shustov
authors.affiliation: Centre for Lymphoid Cancer and Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, BC, Canada.
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Savage
authors.affiliation: Division of Hematology/Oncology, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Vose
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000630:Aminopterin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018450:Disease Progression; D018572:Disease-Free Survival; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D016411:Lymphoma, T-Cell, Peripheral / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: C418863:10-propargyl-10-deazaaminopterin; D015251:Epirubicin; D014750:Vincristine; D003520:Cyclophosphamide; D000630:Aminopterin; D011241:Prednisone
keywords: T-cell lymphoma; clinical trials; therapy