Astragalus-containing Chinese herbal combinations for advanced non-small-cell lung cancer: a meta-analysis of 65 clinical trials enrolling 4751 patients

Jean Jacques Dugoua¹, Ping Wu², Dugald Seely³, Oghenowede Eyawo⁴, Edward Mills<sup>4,5

1</sup>Graduate Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada; ²Shanghai Hospital #4, Shanghai, China; ³Department of Clinical Epidemiology, Canadian College of Naturopathic Medicine; ⁴Faculty of Health Sciences, Simon Fraser University, Burnaby, Canada; ⁵Faculty of Health Sciences, University of Ottawa, Ottawa, Canada

Background: Non-small-cell lung cancer (NSCLC) is a leading cause of death. Interventions to reduce mortality in patients with NSCLC represent a patient-important field of research. Little is known about interventions used outside the Western world for NSCLC. One intervention widely used in Asia is astragalus-based herbal preparations.

Methods: We conducted a comprehensive systematic review of all published randomized clinical trials (RCTs) evaluating astragalus-based herbal preparations in NSCLC patients. We searched independently, in duplicate, 6 English language electronic databases and 2 Chinese-language databases. We abstracted data independently, in duplicate on studies reporting of methods, survival outcomes, tumor responses, and performance score responses. We applied a random-effects meta-analysis and report outcomes as relative risks (RR) with 95% confidence intervals (CIs).

Results: We included 65 RCTs enrolling 4751 patients. All trials included the herbal preparations plus platinum-based chemotherapy versus chemotherapy alone. We pooled 7 studies (n = 529) reporting on survival at 6 months and found a pooled RR of 0.54 (95% CI, 0.45 to 0.65, P ≤ 0.0001). We included 20 trials in (n = 1520) for survival at 12 months and found a pooled RR of 0.65 (95% CI, 0.54 to 0.79, P ≤ 0.0001). This effect was consistent at 24 and 36 months. When we applied a composite endpoint of any tumor treatment response we pooled data from 57 trials and found a pooled RR of 1.35 in favor of herbal treatment (95% CI, 1.26 to 1.44, P ≤ 0.0001). Statistical heterogeneity was low across trials.

Limitations: The quality of reporting the RCTs was generally poor. There is also reason to believe that studies reported as randomized may not be.
Conclusions: We found a large treatment effect of adding astragalus-based herbal treatment to standard chemotherapy regimens. There is a pressing need for validation of these findings in well-conducted RCTs in a Western setting.

Keywords: astralagus, non-small-cell lung cancer, herbal preparations