Yael Waknine

June 21, 2012

June 21, 2012 (Chicago, Illinois) — Ginseng and dexamethasone may offer new hope for patients with cancer fatigue, according to research presented here at the 2012 Annual Meeting of the American Society of Clinical Oncology.

One study, performed in patients with early disease, showed that 8 weeks of daily supplementation with 2000 mg of ground ginseng root led to a 20% decrease in fatigue scores compared with a 10% decrease for placebo (P = .003).

"My goal is to find a regimen of agents that together will work to alleviate fatigue without replacing it with another bunch of side effects. Ginseng is positive in the sense that it reduced fatigue without any side effects relative to placebo that we could discern," lead author Debra Barton, PhD, RN, from the Mayo Clinic College of Medicine in Rochester, Minnesota, told Medscape Medical News in an interview.

Another study, this one in patients with advanced cancer, found that patients taking dexamethasone, 4 mg twice daily, showed significant improvement over placebo at days 8 and 15, in terms of both fatigue and quality of life.

"Our study showed that short-term treatment with dexamethasone is effective for improving quality of life, particularly in patients with more physical distress than psychological distress," lead author Sriram Yennu, MD, MS, from the University of Texas M.D. Anderson Cancer Center in Houston, told Medscape Medical News in an interview. He noted that patients receiving longer-term therapy should be monitored for adverse events, such as edema and myopathy.

Ginseng More Effective During Therapy

For the ginseng study, investigators enrolled 364 patients undergoing or having undergone curative-intent treatment and experiencing cancer-related fatigue (CRF) rated as at least a 4 on a scale of 10 for 1 or more months. Participants were randomly assigned to receive 1000 mg of American ginseng or placebo twice daily.

The primary endpoint was change from baseline in the general subscale of the Multidimensional Fatigue Symptom Inventory (MFSI) at 4 weeks. MFSI subscales (general and physical) and the fatigue-inertia subscale of the Profile of Mood States (POMS) were also analyzed. Data were transformed to a 0 to 100 scale.

Results at 4 weeks revealed a favorable trend for ginseng relative to placebo in terms of improvements in MFSI (4.1 ± 13.4 vs 2.1 ± 12.9; P = .2061), MFSI-general (14.4 ± 27.1 vs 8.2 ± 24.8; P = .0737), MFSI-physical (1.6 ± 15.9 vs -0.4 ± 14.7; P = .3942), and POMS-fatigue/inertia (14.5 ± 25.0 vs 7.7± 23.6; P = .0795) scores.

At 8 weeks, improvements in the general and domains became significant, as demonstrated by the increased scores across all domains: MFSI (6.7 ± 14.0 vs 3.7 ± 14.6; P = .0193), MFSI-general (20.0 ± 27.0 vs 10.3 ± 26.1; P = .0029), MFSI-physical (3.0 ± 17.9 vs -1.7 ± 18.2; P = .0043), and POMS-fatigue/inertia (18.6 ± 24.8 vs 10.2 ± 26.1; P = .0083). No effect on mental, emotional, or vigor dimensions of CRF was observed, and no adverse events were reported by clinicians or patients.

According to Dr. Barton, ginseng had a stronger effect among patients currently undergoing cancer therapy.

"We found a stronger effect among those currently undergoing treatment. It was a little bit surprising to me, but not totally, because it is consistent with how we think ginseng might be helping — which is to decrease inflammatory signals and better regulate cortisol, the stress hormone that has been associated with fatigue and is certainly associated with cancer treatment," Dr. Barton explained.

"It's protective in a way, but not totally protective," she commented, noting that the one thing with the most evidence of protection is exercise.

"Physical activity of almost every kind has been studied and almost everything that's been tried in terms of exercise has been helpful. The challenge is to help motivate patients when they're tired and can't do much," she said.

"In terms of medications there really aren't any that have been consistently proven in studies to be beneficial for cancer related fatigue. A lot of providers use psychostimulants like methylphenidate, but there is no good evidence that they are helpful, and they do have side effects," Dr. Barton added.

According to Dr. Barton, patients should try high-dose ginseng for a month or two before deciding whether it's working for them. Formulations vary with respect to concentration of the active ingredient gincenocide; a 5% formulation of ground American ginseng is recommended. The manner in which ginseng is processed can also make a difference in terms of potency and other characteristics; some extracts are derived with ethanol and have estrogenic characteristics and should not be used by patients with hormone-sensitive disease such as breast cancer.

Dexamethasone Provides Quick Relief

For the dexamethasone study, investigators enrolled 83 patients with advanced cancer who had a CRF rating of 4 of 10 or greater on the Edmonton Symptom Assessment Scale (ESAS) and at least 2 other CRF-related symptoms, such as pain, nausea, appetite, depression, anxiety, or sleep disturbance.

Participants were randomly assigned to receive dexamethasone, 4 mg orally twice a day, for 15 days or placebo, and outcomes were evaluated by using Functional Assessment of Chronic Illness-Fatigue (FACIT-F) subscale scores.

Results demonstrated that dexamethasone significantly improved CRF symptoms from baseline, as evaluated using FACIT-F scores (dexamethasone, 18 ±11 to 27 ±11, P < .001, vs placebo, 21 ± 9 vs 24 ± 12, P = .06).

Dexamethasone also yielded significant improvement relative to placebo on the FACIT-Fatigue (change, 9.6 ± 11 vs 3.1 ± 9.7; P = .005) and ESAS physical distress (P = .02) subscales, but not ESAS overall symptom distress or psychological distress subscales (P = .11 and P = .88, respectively).

The prevalence of serious adverse events did not significantly differ between groups (20 of 42 vs 18 of 47; P = .37).

"The positive [outcome] of the study was that the improvement in fatigue was pretty quick — they showed a difference in as little as 8 days and had benefit at 15 days as well," Dr. Barton commented.

Dr. Barton says she was not surprised by these findings. "Dexamethasone has been known to cause insomnia and improve appetite as side effects. So those aren't necessarily surprising outcomes but it's nice to see those outcomes verified by a randomized controlled study in a specific population," she said.

"Based on findings from this study and a preliminary study we conducted before, I think that it's safe to say that you can use dexamethasone for a short period of time of about 2 weeks. You can give it further for cancer fatigue as tolerated," Dr. Yennu advised.

Dr. Barton agrees.

"I think it would be reasonable for a provider to try dexamethasone for a limited time in an advanced cancer population to see if it was helpful, taking into account the risk/benefit ratio. It ideally should be reserved for patients who are really having fatigue and anorexia and debilitating symptoms to the point that they're really having trouble functioning, enjoying relationships, and staying awake and alert enough to have some quality time."

Both doctors emphasized that longer studies are needed to determine the duration of efficacy and how long it takes for side effects to become bothersome.

2012 Annual Meeting of the American Society of Clinical Oncology (ASCO). Abstracts 9001 and 9002.Presented June 4, 2012.