Clinical Briefs: Astragalus and Chemotherapy
With Comments from Russell H. Greenfield, MD. Dr. Greenfield is Medical Director, Carolinas Integrative Health, Carolinas HealthCare System, Charlotte, NC, and Clinical Assistant Professor, School of Medicine, University of North Carolina, Chapel Hill, NC.
Source: McCulloch M, et al. Astragalus-based Chinese herbs and platinum-based chemotherapy for advanced non-small cell lung cancer: Meta-analysis of randomized trials. J Clin Oncol 2006;24:419-430.
Goal: To assess evidence from published studies and determine whether astragalus-based Chinese herbal medicine offers therapeutic benefit in the setting of lung cancer when combined with platinum-based chemotherapy.
Design: Meta-analysis of randomized trials (n = 34).
Subjects: More than 2,800 subjects with non-small cell lung cancer were assessed in the 34 studies.
Methods: A systematic search of multiple databases without restriction based on language of publication was performed. Out of an initial 1,305 potentially relevant articles identified a total of 34 studies were included in the analysis. Data were assessed for survival outcome, objective tumor response, decreased chemotherapy toxicity, and improved/stabilized performance status.
Results: Twelve trials reported a decreased risk of death at 12 months, while 30 studies reported improved tumor response. A small number of studies also suggested stabilized or improved Karnofsky performance status. No significant data were identified having to do with hematologic toxicity.
Conclusion: Astragalus-based herbal therapy may increase the effectiveness of platinum-based chemotherapy for the treatment of non-small cell lung cancer.
Study strengths: Use of Jadad scale (validated 5-point scale used to evaluate the quality of randomized trials in meta-analysis); conservative nature of assessment of treatment impact; use of Begg test to assess existence of publication bias (none found).
Study weaknesses: Weaknesses inherent in a meta-analysis (for example, some trials employed various combinations of herbs together with astragalus, while others used specific herbal formulas).
Of note: In China, herbal therapies are commonly combined with chemotherapy for the treatment of cancer; Astragalus membranaceus may augment immunity through improved recognition of lung cancer cells (lessened immunologic tolerance to tumor progression) and by stimulating both macrophage and natural killer cell activity; in Chinese medicine, astragalus is almost always used in combination with other Chinese medicinal herbs; though treatment advances continue to be developed, new therapies for non-small cell lung cancer are limited by both significant toxicity and low efficacy; addition of platinum-based drugs to standard chemotherapy has been shown to increase 12-month survival by 5% and tumor response by 62%, but at the expense of significant side effects (nausea and vomiting, renal and hematologic toxicity); only three of 34 studies had a Jadad score of 2 or more (suggesting very poor quality of the studies); there exists no published evidence of interaction between platinum-based chemotherapy and astragalus.
We knew that: Lung cancer is the leading cause of cancer death in the United States; adjuvant chemotherapy reduces risk of death at two years from non-small cell lung cancer by only 13% when compared with treatment by surgery alone, adjuvant chemoradiotherapy reduces the risk by only 14%, and adjuvant radiotherapy alone actually increases the risk of death by 21%; quality of life for people with advanced non-small cell lung cancer is often poor; in a study published in 2003 platinum-based chemotherapy combined with astragalus significantly decreased risk of death at 12 and 24 months (RR = 0.62 and 0.75, respectively).
Clinical import: Astragalus, also known as Huang Qi, has a rich tradition of use in Chinese medicine, especially as an immunostimulant. The data presented in this meta-analysis are far from definitive, especially considering the poor quality of trials assessed, but they are nonetheless compelling in light of the significant therapeutic challenge posed by non-small cell lung cancer. This work does, however, underscore the apparent safety of astragalus, and supports future performance of methodologically sound study of astragalus in combination with chemotherapy. Should practitioners recommend astragalus to their patients who are receiving platinum-based chemotherapy? It is still too early to say with authority. For patients inclined to use herbs or supplements during treatment it is best to include their oncologist in the decision, else the patient could wind up in the middle of divergent medical opinions, adding stress to an already difficult situation.
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