A revisit of prophylactic lamivudine for chemotherapy-associated hepatitis B reactivation in non-Hodgkin's lymphoma: a randomized trial.
Lamivudine is effective to control hepatitis B virus (HBV) reactivation in HBV-carrying cancer patients who undergo chemotherapy, but the optimal treatment protocol remains undetermined. In this study, HBV carriers with newly diagnosed non-Hodgkin's lymphoma (NHL) who underwent chemotherapy were randomized to either prophylactic (P) or therapeutic (T) lamivudine treatment groups. Group P patients started lamivudine from day 1 of the first course of chemotherapy and continued treatment until 2 months after completion of chemotherapy. Group T patients received chemotherapy alone and started lamivudine treatment only if serum alanine aminotransferase (ALT) levels elevated to greater than 1.5-fold of the upper normal limit (ULN). The primary endpoint was incidence of HBV reactivation during the 12 months after starting chemotherapy. During chemotherapy, fewer group P patients had HBV reactivation (11.5% versus 56%, P = 0.001), HBV-related hepatitis (7.7% versus 48%, P = 0.001), or severe hepatitis (ALT more than 10-fold ULN) (0 versus 36%, P < 0.001). No hepatitis-related deaths occurred during protocol treatment. Prophylactic lamivudine use was the only independent predictor of HBV reactivation. After completion of chemotherapy, the incidence of HBV reactivation did not differ between the 2 groups. Two patients, both in group P, died of HBV reactivation-related hepatitis, 173 and 182 days, respectively, after completion of protocol treatment. When compared with an equivalent group of lamivudine-naïve lymphoma patients who underwent chemotherapy, therapeutic use of lamivudine neither reduced the severity of HBV-related hepatitis nor changed the patterns of HBV reactivation.


CONCLUSIONS
Prophylactic lamivudine use, but not therapeutic use, reduces the incidence and severity of chemotherapy-related HBV reactivation in NHL patients.
Hsu
Chiun
C
Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
Hsiung
Chao A
CA
Su
Ih-Jen
IJ
Hwang
Wei-Shou
WS
Wang
Ming-Chung
MC
Lin
Sheng-Fung
SF
Lin
Tseng-Hsi
TH
Hsiao
Hui-Hua
HH
Young
Ji-Hsiung
JH
Chang
Ming-Chih
MC
Liao
Yu-Min
YM
Li
Chi-Cheng
CC
Wu
Hung-Bo
HB
Tien
Hwei-Fang
HF
Chao
Tsu-Yi
TY
Liu
Tsang-Wu
TW
Cheng
Ann-Lii
AL
Chen
Pei-Jer
PJ
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D006509:Hepatitis B / Q000188:drug therapy / Q000401:mortality / Q000517:prevention & control*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008228:Lymphoma, Non-Hodgkin / Q000150:complications* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D055502:Secondary Prevention; D016019:Survival Analysis; D016896:Treatment Outcome
D000998:Antiviral Agents; D019259:Lamivudine