title: Pegylated liposomal doxorubicin replacing conventional doxorubicin in standard R-CHOP chemotherapy for elderly patients with diffuse large B-cell lymphoma: an open label, single arm, phase II trial.
abstract: BACKGROUND
  The present multicenter phase II trial evaluated the safety and efficacy of pegylated liposomal doxorubicin (PLD) instead of conventional doxorubicin in standard R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine [Oncovin], and prednisone) therapy for elderly patients with diffuse large B-cell lymphoma.
  
  
  METHODS
  Patients aged > 60 years who had stage II to IV disease were included. Treatment consisted of rituximab 375 mg/m(2) intravenously (I.V.); cyclophosphamide 750 mg/m(2) IV; PLD 40 mg/m(2) (maximum, 90 mg) I.V. over 1 hour; and vincristine 2.0 mg I.V., all on day 1. Additionally prednisone, 40 mg/m(2), was given orally on days 1 to 1 to 5 (DRCOP [rituximab, cyclophosphamide, PLD, vincristine, and prednisone]). The cycles were repeated every 3 weeks for 6 to 8 cycles.
  
  
  RESULTS
  Eighty patients were enrolled and were evaluable for toxicity. The median age was 69 years. All except 1 had additional cardiac risk factors for anthracycline-induced cardiac toxicity beyond advanced age. From the intent-to-treat analysis of 79 eligible patients, the overall response rate was 86%, and the complete response rate was 78%. Cardiac events greater than grade 3 were identified in 3 patients (4%); grade 1 to 2 events, mostly asymptomatic declines in ejection fraction, were noted in another 16 patients. One death was attributed to cardiac failure. The estimated 5-year event-free and overall survival rate was 52% and 70%, respectively.
  
  
  CONCLUSIONS
  DRCOP represents an effective strategy for potentially mitigating cardiotoxicity in elderly patients with aggressive B-cell lymphoma. Future studies incorporating baseline cardiac risk assessments, long-term follow-up data, and biospecimen collection for correlative science should be undertaken.
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address: yoki@mdanderson.org.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Oki
authors.affiliation: Department of Cardiology, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Ewer
authors.affiliation: Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lenihan
authors.affiliation: Department of General Oncology, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Fisch
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Fredrick B
authors.initials: FB
authors.lastname: Hagemeister
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Michelle
authors.initials: M
authors.lastname: Fanale
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Jorge
authors.initials: J
authors.lastname: Romaguera
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Barbara
authors.initials: B
authors.lastname: Pro
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Nathan
authors.initials: N
authors.lastname: Fowler
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Anas
authors.initials: A
authors.lastname: Younes
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Maimonides Medical Center, Brooklyn, NY.
authors.forename: Alan B
authors.initials: AB
authors.lastname: Astrow
authors.affiliation: Department of Biomathematics, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Xuelin
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Larry W
authors.initials: LW
authors.lastname: Kwak
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Felipe
authors.initials: F
authors.lastname: Samaniego
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Peter
authors.initials: P
authors.lastname: McLaughlin
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Sattva S
authors.initials: SS
authors.lastname: Neelapu
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Michael
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Fayad
authors.affiliation: Department of Cardiology, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Jean-Bernard
authors.initials: JB
authors.lastname: Durand
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: M Alma
authors.initials: MA
authors.lastname: Rodriguez
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015897:Comorbidity; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D018450:Disease Progression; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D057915:Drug Substitution; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D000069283:Rituximab; D016896:Treatment Outcome; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; C571759:R-CHOP protocol; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone
keywords: Anthracycline; Cardiac toxicity; Diffuse large B-cell lymphoma; Elderly patients; Pegylated liposomal doxorubicin