In a collaborative phase III trial of the North Central Cancer Treatment Group and Mayo Clinic (N07C2) reported in Journal of the National Cancer Institute by Debra L. Barton, RN, PhD, AOCN, FAAN, of the Mayo Clinic and colleagues, patients with cancer-related fatigue were treated with Wisconsin ginseng (a common type of American ginseng) or placebo.1 Fatigue was significantly reduced in ginseng recipients at 8 weeks, and no discernible toxicities were associated with ginseng treatment.
Study Details
In this double-blind multi-institution study, 341 patients with cancer-related fatigue received 2,000 mg of Wisconsin ginseng in two daily doses (n = 171) or placebo (n = 170) for 8 weeks. Fatigue was defined as a score of ≥ 4 on a scale on which 0 indicates no fatigue and 10 indicates fatigue “as bad as it can be.”
Patients with all cancers, other than brain or central nervous system lymphoma, who were undergoing or had undergone curative treatment and who had been diagnosed within the past 2 years were eligible for the study. Those currently receiving cancer treatment could not be scheduled to change treatment status during the trial. Patients could not be receiving systemic steroids, opioids, prior/current ginseng, or other agents for fatigue.
The primary endpoint was change from baseline in the general subscale of the Multidimensional Fatigue Symptom Inventory–Short Form (MFSI-SF) at 4 weeks.
There were no significant differences between the ginseng and placebo groups at baseline for age (mean, 55 and 56 years), sex (81% and 75% female), race (91% and 92% white), menopausal status (22% and 18% premenopausal), type of cancer (breast in 64% and 57%, colon in 12% and 10%), or proportions currently receiving cancer treatment (49% in both groups). Somewhat more patients in the ginseng group were taking sleep aids (25% vs 17%). There were no significant differences between the two groups in baseline scores for MFSI-SF subscales or total score.
Fatigue Significantly Reduced at 8 Weeks
At 4 weeks, mean (standard deviation) changes from baseline in the general subscale of the MFSI-SF were 14.4 points (27.1) in the ginseng group (n = 147 evaluable) and 8.2 points (24.8) in the placebo group (n = 153 evaluable; P = .07). At 8 weeks, changes were 20 points (27) in the ginseng group (n = 138 evaluable) and 10.3 points (26.1) in the placebo group (n = 133 evaluable; P = .003).
Among patients currently undergoing cancer therapy, ginseng was associated with significant improvement in fatigue at both 4 weeks (P = .02) and 8 weeks (P = .01). More patients had a positive response to ginseng and more had a strong clinical benefit (≥ 30% improvement) compared with placebo.
With regard to secondary endpoints, significant improvements in ginseng patients were observed at 8 weeks in the MFSI-SF physical subscale, MFSI-SF total score, and the Profile of Mood States (POMS) fatigue inertia subscale. No differences between groups were observed on the MFSI-SF mental, emotional, or vigor subscales or POMS vigor activity subscale.
No Appreciable Toxicity
Only five toxicities with a greater than 1% incidence were attributed to study treatments, consisting of nausea in 3% of ginseng patients and 2% of placebo patients, vomiting in 1% and 1%, insomnia on 6% and 7%, anxiety in 2% and 3%, and agitation in 1% and 2%. All of these adverse events were moderate except for severe insomnia in one patient in each group.
As noted by the authors, preclinical data suggest that ginseng may act by downregulating inflammatory pathways, thereby decreasing inflammation, and modulating cortisol and the impact of chronic stress on the hypothalamic pituitary adrenal axis. Among the active ingredients in ginseng, the most important appears to be ginsensosides, and it is important to note that amounts and strengths of ginsensosides vary among species and batches of ginseng.
Preclinical data indicate that American ginseng does not interfere with tamoxifen, doxorubicin, cyclophosphamide, paclitaxel, fluorouracil, or methotrexate. Some data indicate that the herb is synergistic with these agents against MCF-7 breast cancer cell lines.
The investigators concluded: “Data from this study support that American ginseng has activity against [cancer-related fatigue] but that clinically meaningful results may not be realized until 2 months after starting ginseng…. [A]lthough this study provides support for the use of American ginseng to ameliorate [cancer-related fatigue], more research is necessary to understand its role and how to maximize its positive effects. It would, however, be reasonable for a cancer survivor to try American ginseng for fatigue, taking into consideration that there are no other pharmacologic agents known to be effective.” ■
Disclosure: For study funding information, visit jnci.oxfordjournals.org.
Reference
1. Barton DL, Liu H, Dakhil SR, et al: Wisconsin ginseng (Panax quinquefolius) to improve cancer-related fatigue. J Natl Cancer Inst. July 13, 2013.
