Barton, D. L., Soori, G. S., Bauer, B. A., Sloan, J. A., Johnson, P. A., Figueras, C., . . . Loprinzi, C. L. (2010). Pilot study of Panax quinquefolius (American ginseng) to improve cancer-related fatigue: a randomized, double-blind, dose-finding evaluation: NCCTG trial N03CA. Supportive Care in Cancer, 18, 179–187.

To determine whether any of three specific doses of American ginseng help cancer-related fatigue, as well as to evaluate toxicity.

Patients were randomized to receive ginseng doses of 750, 1,000, or 2,000 mg per day or placebo. Doses were given in twice daily dosing over eight weeks. The ginseng used was Wisconsin ginseng that met quality-control requirements for pesticides and contaminants. Specific description of ginsenosides content is described. 

Outcome measures were obtained at baseline, four weeks, and eight weeks. Patients were stratified according to stage of disease, gender, baseline fatigue score, and current treatment. Randomization assignments were computer-generated using a dynamic allocation procedure for distribution of stratification factors.

• In total, 175 patients (66% female) with a history of chronic fatigue completed the study. 
• Mean age across study groups ranged from 58 to 62 years (standard deviation [SD] = 12).
• Patient diagnoses were predominantly breast, colon, and lung cancer.
• Of the patients, 62% had stage III/IV disease.
• Of the patients, 71% had a baseline fatigue score of 4 to 7.
• Of the patients, 65% had previous chemotherapy.
• Of the patients, 57% were receiving current chemotherapy and 18% were receiving current radiotherapy.
• No significant differences existed between groups in demographic, disease, or treatment characteristics.

This was a multisite collaborative trial of the North Central Cancer Treatment group and the Mayo Clinic.

This was a randomized, double-blind, placebo-controlled study.

• Brief Fatigue Inventory (BFI)
• Vitality subscale of the Medical Outcome Scale (MOS) Short Form (SF-36)
• Global Impression of Benefit Scale
• Pittsburgh Sleep Quality Index (PSQI)
• Global Impression of Change
• Linear Analogue Scale
• Toxicities were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0 (NCI CTCAE)
• Patients completed weekly self reports of toxicities in a symptom experience diary to rate side effects on a 0 to 10 scale, with higher scores indicating greater severity.

• Mean scores for the SF-36 subscale between collective ginseng arms and placebo were not significantly different. A trend was observed for greater positive effects at the highest ginseng dose.
• Analysis of change in fatigue showed a greater effect on fatigue with the highest two dose groups, but this was not statistically significant.
• A trend was observed for greatest effect on quality of life measures at the highest ginseng doses.
• The greatest PSQI improvement over time occurred in the placebo group.
• Patient subjective perception of benefits showed an overall trend of higher benefit in the two highest ginseng dosage groups.
• No significant toxicities were associated with the use of ginseng.

Findings suggest that ginseng at the dose of 750 mg per day did not provide any benefit over that of placebo. At the two highest doses of ginseng, a trend was observed of decreased fatigue compared to placebo.

• The study was powered as a pilot study to evaluate composite ginseng dose groups versus placebo, so dose-related findings were underpowered to show statistical significance. 
• A challenge in studying herbal supplements is the lack of standardization and variability in content affected by growing conditions, so the findings may not be generalizable to use of ginseng grown elsewhere or under different climactic conditions.

The preliminary evidence here suggests that the improvement in patient perception with ginseng versus placebo is that this effect may have broad benefit to patients, even if objective measures of outcomes are nonsignificant. It would be worthwhile to more clearly and definitively evaluate the benefits of ginseng in additional larger, more definitive clinical trials.