Tang, W., Chen, L., Zheng, R., Pan, L., Gao, J., Ye, X., . . . Zheng, W. (2015). Prophylactic effect of lamivudine for chemotherapy-induced hepatitis B reactivation in breast cancer: A meta-analysis. PLOS One, 10, e0128673. 

DOI Link

Purpose

STUDY PURPOSE: To determine the effect of prophylactic or preemptive treatment with lamivudine for patients with breast cancer who were hepatitis B surface antigen positive on the following: (a) the rate of hepatitis B virus (HBV) reactivation, which was defined as an increase in HBV DNA levels more than 10 times or an absolute increase of HBV DNA levels that exceeded 1×109 copies/ml; (b) incidence of hepatitis, which was defined as greater than a three times increase in alanine aminotransferase (ALT) that exceeded the upper limit of normal range (ULN) or an absolute increase of ALT of more than 100 u/l; (c) rate of chemotherapy disruption, which was defined as either a premature termination of chemotherapy or a delay of more than eighty days of chemotherapy between cycles; and (d) overall mortality. Secondary outcomes included incidence of HBV-related hepatitis, rate of HBV-related chemotherapy disruption, HBV-related mortality, occurrence of YMDD mutations, and withdrawal hepatitis.

TYPE OF STUDY: Meta-analysis and systematic review

Search Strategy

DATABASES USED: All relevant articles were retrieved from PubMed, Embase, MEDLINE, Ovid, and the Central Registry of Controlled Trials of the Cochrane Library using a combination of the terms chemotherapy, lamivudine, cancer, carcinoma, neoplasm, malignant, and breast.
 
INCLUSION CRITERIA: Trials that compared lamivudine as a prophylactic or preemptive treatment (as defined in each trial) for patients who were hepatitis B surface antigen (HBsAg)-positive with breast cancer who received systemic chemotherapy
 
EXCLUSION CRITERIA: Case reports, reviews, and conference reports; studies without a control group; studies that were unable to provide clear baseline characteristics; patients with hepatitis C virus (HCV), hepatitis D virus (HDV), or human immunodeficiency virus (HIV) co-infection

Literature Evaluated

TOTAL REFERENCES RETRIEVED: 16
 
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: One prospective, randomized, controlled study; two retrospective cohort studies; and one prospective, one-arm trial with a historical control

Sample Characteristics

  • FINAL NUMBER STUDIES INCLUDED = 6
  • TOTAL PATIENTS INCLUDED IN REVIEW = 430
  • SAMPLE RANGE ACROSS STUDIES: 43–50 patients (median range)
  • KEY SAMPLE CHARACTERISTICS: Patients with breast cancer undergoing systemic chemotherapy who were HBV carriers (HBsAg)

Phase of Care and Clinical Applications

PHASE OF CARE: Active antitumor treatment
 
APPLICATIONS: Elder care

Results

Application of early preemptive lamivudine was superior in reducing HBV recurrence (pooled odds ratio [OR] = 0.12, 95% confidence interval [CI] [0.04, 0.31], p < 0.0001), the incidence of HBV-related hepatitis (pooled OR = 0.13, 95%CI [0.04, 0.37], p < 0.0001), and the rate of chemotherapy disruption (pooled OR = 0.37, 95% CI [0.23, 0.6], p < 0.0001). In these two groups, no significant difference was found in overall mortality (p = 0.32), YMDD mutant rate (p = 0.13), or incidence of withdrawal hepatitis (p = 0.38). In the the early preemptive strategy, lamivudine was given at the commencement of chemotherapy. In the therapeutic strategy, lamivudine treatment was started after the development of a clinical hepatitis flare-up.

Conclusions

An early preemptive strategy is superior to a therapeutic strategy in decreasing the incidence of HBV reactivation, HBV-related hepatitis, and the rate of chemotherapy disruption in patients with breast cancer.

Limitations

  • Limited search
  • High heterogeneity

Nursing Implications

In this study, 16% of patients who were HBsAg positive undergoing chemotherapy for breast cancer developed overt hepatitis. Using a preemptive strategy of prescribing lamivudine at the commencement of chemotherapy decreased the rate of hepatitis to 2.2%. The authors noted that, as level III evidence, the AASLD (American Association for the Study of Liver Diseases) recommends that HBV carriers receiving cancer chemotherapy or immunosuppressive therapy with a baseline HBV DNA of less than 2,000 iu/ml should start antiviral therapy at the commencement of treatment and continue it for six months after the completion of chemotherapy or immunosuppressive therapy.

Legacy ID

6058