title: Entecavir vs lamivudine for prevention of hepatitis B virus reactivation among patients with untreated diffuse large B-cell lymphoma receiving R-CHOP chemotherapy: a randomized clinical trial.
abstract: OBJECTIVE
  Hepatitis B virus (HBV) reactivation is a serious complication for patients with lymphoma treated with rituximab-containing chemotherapies, despite lamivudine prophylaxis treatment. An optimal prophylactic antiviral protocol has not been determined.
  
  
  OBJECTIVE
  To compare the efficacy of entecavir and lamivudine in preventing HBV reactivation in patients seropositive for the hepatitis B surface antigen with untreated diffuse large B-cell lymphoma receiving chemotherapy treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).
  
  
  METHODS
  Randomized, open-label, phase 3 study conducted from February 2008 through December 2012 at 10 medical centers in China. This study was a substudy of a parent study designed to compare a 3-week with a 2-week R-CHOP chemotherapy regimen for untreated diffuse large B-cell lymphoma. Patients enrolled in the parent study who were seropositive for the hepatitis B surface antigen and had normal liver function, serum HBV DNA levels of less than 103 copies/mL, and no prior antiviral therapy were randomized to entecavir (n = 61) or lamivudine (n = 60).
  
  
  METHODS
  Daily entecavir (0.5 mg) or lamivudine (100 mg) beginning 1 week before the initiation of R-CHOP treatment to 6 months after completion of chemotherapy.
  
  
  METHODS
  The primary efficacy end point was the incidence of HBV-related hepatitis. The secondary end points included rates of HBV reactivation, chemotherapy disruption due to hepatitis, and treatment-related adverse events.
  
  
  RESULTS
  There were 121 patients randomly assigned to receive entecavir (n = 61) or lamivudine (n = 60). The date of last patient follow-up was May 25, 2013. The rates were significantly lower for the entecavir group vs the lamivudine group for HBV-related hepatitis (0% vs 13.3%, respectively; difference between groups, 13.3% [95% CI, 4.7% to 21.9%]; P = .003), HBV reactivation (6.6% vs 30%; difference, 23.4% [95% CI, 10.2% to 36.6%]; P = .001), and chemotherapy disruption (1.6% vs 18.3%; difference, 16.7% [95% CI, 6.4% to 27.0%]; P = .002). Of the 61 patients in the entecavir group, 15 (24.6%) experienced treatment-related adverse events. Of 60 patients in the lamivudine group, 18 (30%) experienced treatment-related adverse events (difference between entecavir and lamivudine groups, 5.4% [95% CI, -10.5% to 21.3%]; P = .50).
  
  
  CONCLUSIONS
  Among patients seropositive for the hepatitis B surface antigen with diffuse large B-cell lymphoma undergoing R-CHOP chemotherapy, the addition of entecavir compared with lamivudine resulted in a lower incidence of HBV-related hepatitis and HBV reactivation. If replicated, these findings support the use of entecavir in these patients.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01793844; Chinese Clinical Trial Registry Identifier: CTR-TRC-11001687.
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Xueying
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Beijing Cancer Hospital, Beijing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Medical Oncology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Ye
authors.affiliation: Department of Medical Oncology, Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Cancer Center of the First People's Hospital of Foshan, Foshan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiangyuan
authors.initials: X
authors.lastname: Wu
authors.affiliation: Cancer Center of People's Hospital of Zhongshan, Zhongshan, China.
authors.forename: Jiewen
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Hematology, Southern Hospital of Southern Medical University, Guangzhou, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Medical Oncology, Cancer Hospital, Shantou University Medical College, Shantou, China.
authors.forename: Yingcheng
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Cancer Center of Kiang Wu Hospital, Macau, China.
authors.forename: Yabing
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Haoran
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Suxia
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Epidemiology and Biostatistics, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Tongyu
authors.initials: T
authors.lastname: Lin
mesh_terms: D000328:Adult; D000368:Aged; 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*; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006509:Hepatitis B / Q000209:etiology / Q000517:prevention & control*; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000821:virology; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D000069283:Rituximab; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; C571759:R-CHOP protocol; D019259:Lamivudine; D000069283:Rituximab; C413685:entecavir; D014750:Vincristine; D006147:Guanine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone