Reference
Barton DL, Liu H, Dakhil SR, et al. Wisconsin Ginseng (Panax quinquefolius) to improve cancer-related fatigue: a randomized, double-blind trial, N07C2. J Natl Cancer Inst. 2013;105(16):1230-1238.
Design
An 8-week multisite, randomized, double-blind, placebo-controlled study using 1000 mg twice daily of Panax quinquefolius (American ginseng) vs placebo in cancer patients with cancer-related fatigue (CRF). Assessment of fatigue symptoms, secondary outcomes, and toxicities were assessed.
Participants
This study evaluated 364 non-brain or central nervous system lymphoma cancer patients at 40 sites suffering from CRF (qualified as a score of 4 or more on an 11-point scale) with a mean age of 55. In both arms, greater than 75% of patients were female, greater than 90% were Caucasian, roughly 50% of subjects were currently undergoing cancer treatment, a little more than 50% were regular exercisers, and the distributions of cancer types ranged from breast (60%), colon (11%), prostate (4%), hematological (5%), gynecological (4%), and combined/other (16%). There was no statistical significance in fatigue scores between groups.
Outcome Measures
The primary outcome measure was fatigue assessed by the Multidimensional Fatigue Symptoms Inventory-Short Form. Secondary outcomes included the Profile of Mood States fatigue-inertia and vigor-activity subscales, the Brief Fatigue Inventory, and self-reported side effects.
Key Findings
Comparing placebo vs the P guinquefolius intervention, the group receiving ginseng demonstrated significant improvement in fatigue at 8 weeks, with greater benefit reported in patients receiving active treatment than those who had completed treatment.
Side effects of moderate agitation, anxiety, insomnia, nausea, and vomiting were reported in both treatment and placebo groups. The most common side effect was moderate nausea in 5% of subjects in the treatment group with no statistical difference of all side effects between groups, suggesting that P quinquefolius is a safe and tolerable intervention for the treatment of CRF.
Clinical Implications
In a systematic review using control group comparisons, Prue and colleagues found the prevalence of fatigue to be between 39% and 90% in cancer patients undergoing anticancer therapy, with fatigue occurring up to 5 years after completion of adjuvant treatment in some studies. In advanced stages of cancer, 78% of palliative care patients report having severe fatigue.1
In the management of patients with cancer, fatigue is a common symptom requiring appropriate assessment and intervention to help relieve its impact on quality of life.
To date, few randomized controlled trials of nonpharmacological or pharmacological interventions for improving fatigue in cancer patients have been performed. The most well-researched interventions for CRF are outlined in the National Comprehensive Cancer Network guidelines (updated in 2013), which includes exercise; psychosocial interventions (stress management, relaxation, and support groups); sleep restoration interventions; treatment of potential contributing factors (anemia, pain, malnutrition); or a therapeutic trial of methylphenidate.2
A 2012 Cochrane Review concluded there is no convincing evidence for a clear improvement in subjective fatigue with exercise used as an intervention.3 However, with the potential for fewer safety concerns compared to pharmacotherapy and the multitude of other health parameter benefits, regular aerobic exercise should be included in every treatment plan.
Pharmacological intervention for CRF often includes 6 different classes of medication, including hematopoietic growth factors, psychostimulants, bisphosphonates, anti-TNF-α antibodies, antidepressants, and steroids. Little to no benefit has been found with many of these drugs, with the exception of erythropoietin and darbepoetin, which are most likely playing more of an important corrective role in the management of cancer-related anemia.4,5 Due to the ineffectiveness of many of these medications at managing CRF, there is room for effective natural agents with better safety profiles to be used therapeutically.
Though much of the clinical research looking at the fatigue response with ginseng administration has been with Panax ginseng (Asian ginseng),6 P quinquefolius was chosen for this investigation due to its similar ginsenosides (Rb1 and Rg1), which have been found to enhance activity performance in mice, have favorable toxicity reports in the literature, and have respectable quality assurance and available sourcing opportunities.7
In the management of patients with cancer, fatigue is a common symptom requiring appropriate assessment and intervention to help relieve its impact on quality of life.8 There is now emerging evidence for effective CRF treatment options with acceptable safety profiles, such as with this recently published article on P quinquefolius.
Though the results in this study are favorable for the treatment of CRF, it would have been even more interesting if interventions were administered for longer periods, as some CRF studies have reported fatigue occurring up to 5 years after completion of cancer therapy.
