[Chinese herbal medicine for side effects of transarterial chemoembolization in liver cancer patients: a systematic review and meta-analysis].

BACKGROUND: Primary liver cancer is one of the most commonly seen tumors in clinical practice. Due to the stealthiness and fast progress of liver cancer, only 20% of the patients may have chance to receive operation for radical therapy. Patients seldom get benefit from systematic chemotherapy and as a result, local chemotherapy methods such as transarterial chemoembolization (TACE) have become the mainstay in the treatment of liver cancer. Compared with systematic chemotherapy, TACE produces fewer side effects and most of such side effects are caused by postembolization syndrome manifested as nausea and vomiting, abdominal pain, fever, loss of appetite, etc.

OBJECTIVE: In this systematic review, effects of Chinese herbal medicine (CHM) in relieving side effects caused by TACE in patients with liver cancer were evaluated and meta-analysis was conducted when possible.

SEARCH STRATEGY: Literature search was conducted on August 23rd, 2011. The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials in the Cochrane Library, MEDLINE (Ovid SP), EMBASE (Ovid SP), and Science Citation Index Expanded, China National Knowledge Infrastructure Database, Chongqing VIP Database and Wanfang Data were searched with no time limits.

INCLUSION CRITERIA: Randomized clinical trials (RCTs) of CHM for TACE-induced side effects in patients with primary liver cancer were eligible for this review, regardless of blinding, language, or publication status.

DATA EXTRACTION AND ANALYSIS: Search results were screened to select the trials included in this review according to the inclusion criteria, and data were extracted from all the included RCTs by using a self-developed data extraction form. Assessment of risk of bias in included studies was conducted according to the Cochrane Handbook for Systematic Reviews of Intervention (Version 5.0.2): Criteria for judging risk of bias in the "risk of bias" assessment tool. Dichotomous data were expressed as risk ratio with its 95% confidence interval (CI). Continuous outcomes were expressed as mean differences with 95% CI. If there was no significant heterogeneity, the results from the fixed-effect model were presented. If the heterogeneity was not substantial, the results from the random-effect model were presented. If the heterogeneity was substantial, a meta-analysis was not performed and a narrative, qualitative summary was performed instead. In the event of substantial clinical, methodological, or statistical heterogeneity, the trial components such as patients, diseases, interventions, comparisons, and outcomes in the included trials were reviewed to decide the reason for heterogeneity.

RESULTS: A total of 47 RCTs were included in this review after screening the search results. Among them, 46 were in Chinese and 1 was in English; 43 were journal articles and 4 were academic dissertations; all the authors were from mainland China and all the trials were conducted in mainland China. The results of assessment of risk of bias showed that there was unclear or high risk of bias in most of the included RCTs and thus they were all with low quality. The results of systematic evaluation and meta-analysis showed that CHM was beneficial to patients with liver cancer in prolonging life expectancy, improving quality of life, reducing side effects of TACE such as nausea and vomiting, fever, liver pain, and bone marrow suppression, improving liver function indexes and immunological indexes, and enhancing objective curative effect on the tumor size. However, due to the substantial heterogeneity presented in most of the indexes, only descriptive analysis was conducted for these indexes. The results of the heterogeneity analysis showed that the causes of substantial heterogeneity may be due to the obvious difference in treatment protocol, components and dosage form of CHM, time for delivering drugs and course of treatment.

CONCLUSION: CHM is effective in prolonging life expectancy, improving quality of life, and reducing side effects of TACE in the treatment of liver cancer. However, due to the undesirable quality of the included RCTs and the substantial heterogeneity, most of the outcome measure indexes were failed to be meta-analyzed, and thus the significance of this review for clinical practice was limited.