Pilot study of Panax quinquefolius (American ginseng) to improve cancer-related fatigue: a randomized, double-blind, dose-finding evaluation: NCCTG trial N03CA

Abstract

Purpose

This pilot trial sought to investigate whether any of three doses of American ginseng (Panax quinquefolius) might help cancer-related fatigue. A secondary aim was to evaluate toxicity.

Methods

Eligible adults with cancer were randomized in a double-blind manner, to receive American ginseng in doses of 750, 1,000, or 2,000 mg/day or placebo given in twice daily dosing over 8 weeks. Outcome measures included the Brief Fatigue Inventory, vitality subscale of the Medical Outcome Scale Short Form-36 (SF-36), and the Global Impression of Benefit Scale at 4 and 8 weeks.

Results

Two hundred ninety patients were accrued to this trial. Nonsignificant trends for all outcomes were seen in favor of the 1,000- and 2,000-mg/day doses of American ginseng. Area under the curve analysis of activity interference from the Brief Fatigue Inventory was 460–467 in the placebo group and 750 mg/day group versus 480–551 in the 1,000- and 2,000-mg/day arms, respectively. Change from baseline in the vitality subscale of the SF-36 was 7.3–7.8 in the placebo and the 750-mg/day arm, versus 10.5–14.6 in the 1,000- and 2,000-mg/day arms. Over twice as many patients on ginseng perceived a benefit and were satisfied with treatment over those on placebo. There were no significant differences in any measured toxicities between any of the arms.

Conclusion

There appears to be some activity and tolerable toxicity at 1,000–2,000 mg/day doses of American ginseng with regard to cancer-related fatigue. Thus, further study of American ginseng is warranted.

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References

  1. 1.

    NCCN Cancer Related Fatigue Clinical Practice Guidelines in Oncology V.1.2003. http://www.nccn.org/

  2. 2.

    Mock V (2001) Fatigue management, evidence and guidelines for practice. Cancer 92(6):1699–1707. doi:10.1002/1097-0142(20010915) 92:6+<1699::AID-CNCR1500>3.0.CO;2-9

    Article  CAS  PubMed  Google Scholar 

  3. 3.

    Fulton C, Knowles G (2000) Cancer fatigue. Eur J Cancer Care (Engl) 9(3):167–171

    CAS  Google Scholar 

  4. 4.

    Gutstein HB (2001) The biological basis of fatigue. Cancer 92(6):1678–1683. doi:10.1002/1097-0142(20010915) 92:6+<1678::AID-CNCR1496>3.0.CO;2-R

    Article  CAS  PubMed  Google Scholar 

  5. 5.

    Berger AM, Farr LA, Kuhn BR, Fischer P, Agrawal S (2007) Values of sleep/wake, activity/rest, circadian rhythms, and fatigue prior to adjuvant breast cancer chemotherapy. J Pain Symptom Manage 33(4):398–409. doi:10.1016/j.jpainsymman.2006.09.022

    Article  PubMed  Google Scholar 

  6. 6.

    Lawrence DP, Kupelnick B, Miller K, Devine D, Lau J (2004) Evidence report on the occurrence, assessment, and treatment of fatigue in cancer patients. J Natl Cancer Inst Monogr 32:40–50. doi:10.1093/jncimonographs/lgh027

    Article  PubMed  Google Scholar 

  7. 7.

    Bower JE, Ganz PA, Desmond KA, Rowland KA, Meyerowitz JH, Belin BE, Thomas R (2000) Fatigue in breast cancer survivors: occurrences, correlates, and impact on quality of life. J Clin Oncol 18:743–753

    CAS  PubMed  Google Scholar 

  8. 8.

    Bower JE, Ganz PA, Desmond KA, Bernaards C, Rowland JH, Meyerowitz BE, Belin TR (2006) Fatigue in long-term breast carcinoma survivors. A longitudinal investigation. Cancer 106:751–758. doi:10.1002/cncr.21671

    Article  PubMed  Google Scholar 

  9. 9.

    Baker F, Denniston M, Smith T, West MM (2005) Adult cancer survivors: how are they faring. Cancer 104(Suppl 11):2565–2576. doi:10.1002/cncr.21488

    Article  PubMed  Google Scholar 

  10. 10.

    Mitchell SA, Beck SL, Edward Hood L, Moore K, Tanner ER (2007) Putting evidence into practice: evidence-based interventions of fatigue during and following cancer and its treatment. Clin J Oncol Nurs 11(1):99–113. doi:10.1188/07.CJON.99-113

    Article  PubMed  Google Scholar 

  11. 11.

    Mitchell SA, Berger AM (2006) Cancer-related fatigue: the evidence base for assessment and management. Cancer J 12:374–387. doi:10.1097/00130404-200609000-00007

    Article  PubMed  Google Scholar 

  12. 12.

    Mock V, Pickett M, Ropka M, Lin E, Grimm P, Rhodes V, McDaniel R, Grimm PM, Krumm S, McCorkle R (2001) Fatigue, physical functioning, emotional distress, and quality of life outcomes of a walking intervention during breast cancer treatment. Cancer Pract 9:119–127. doi:10.1046/j.1523-5394.2001.009003119.x

    Article  CAS  PubMed  Google Scholar 

  13. 13.

    Schwartz AL, Mori M, Gao R, Nail R, King LM, Marjorie E (2001) Exercise reduces daily fatigue in women with breast cancer receiving chemotherapy. Med Sci Sports Exerc 33:718–723. doi:10.1097/00005768-200105000-00006

    Article  CAS  PubMed  Google Scholar 

  14. 14.

    Stone P, Richards M, Hardy J (1998) Fatigue in patients with cancer. Eur J Cancer 34(11):1670–1676. doi:10.1016/S0959-8049(98)00167-1

    Article  CAS  PubMed  Google Scholar 

  15. 15.

    Portenoy RK, Itri LM (1999) Cancer-related fatigue: guidelines for evaluation and management. Oncologist 4:1–10

    CAS  PubMed  Google Scholar 

  16. 16.

    Burks TF (2001) New agents for the treatment of cancer-related fatigue. Cancer 92(Suppl 6):1714–1718. doi:10.1002/1097-0142(20010915)92:6+<1714::AID-CNCR1502>3.0.CO;2-N

    Article  CAS  PubMed  Google Scholar 

  17. 17.

    Bruera E, Driver L, Barnes EA, Willey J, Shen L, Palmer JL, Escalante C (2003) Patient-controlled methylphenidate for the management of fatigue in patients with advanced cancer: a preliminary report. J Clin Oncol 21(23):4439–4443. doi:10.1200/JCO.2003.06.156

    Article  CAS  PubMed  Google Scholar 

  18. 18.

    Bruera E, Valero V, Driver L, Shen L, Willey J, Zhang T, Palmer JL (2006) Patient-controlled methylphenidate for cancer fatigue: a double-blind, randomized, placebo-controlled trial. J Clin Oncol 24(13):2073–2078. doi:10.1200/JCO.2005.02.8506

    Article  CAS  PubMed  Google Scholar 

  19. 19.

    Bruera E, Osta E, Vlaero V, Driver L, Palmer J, Pei B, Shen L, Poulter V (2007) Donepezil for cancer-related fatigue: a double-blind, randomized, placebo-controlled study. J Clin Oncol 25(23):3475–3481, Part I II 493s(9003)

    Article  CAS  PubMed  Google Scholar 

  20. 20.

    Stankoff B, Waubant E, Confavreau C, Edan G, Debouverie M, Rumback L, Moreau Tl, Pelletier J, Lubetzki C, Clanet M, French Modafinil Study Group (2005) Modafinil for fatigue in MS: a randomized placebo-controlled double blind study. Neurology 64:1139–1143

    CAS  PubMed  Google Scholar 

  21. 21.

    Attele AS, Wu JA, Yuan C (1999) Ginseng pharmacology. Biochem Pharmacol 58:1685–1693. doi:10.1016/S0006-2952(99)00212-9

    Article  CAS  PubMed  Google Scholar 

  22. 22.

    Ginseng (American ginseng, Asian ginseng, Chinese ginseng, Korean red ginseng, Panax ginseng: Panax spp. Including P. ginseng C.C. Meyer and P. quinquefolius L., excluding Eleutherococcus senticosus). http://natuaralstandard.com/monographys/herssupplements/ginseng.asp. Accessed on 4 April 2007

  23. 23.

    Cui J (1995) Identification and quantification of ginsenosides in various commercial ginseng preparations. Eur J Pharm Sci 3:77–85. doi:10.1016/0928-0987(94)00077-D

    Article  CAS  Google Scholar 

  24. 24.

    Tadano T, Nakagawasai O, Niijima F, Tan-No K, Kisara K (2000) The effects of traditional tonics on fatigue in mice differ from those of the antidepressant imipramine: a pharmacological and behavioral study. Am J Chin Med 28(1):97–104. doi:10.1142/S0192415X0000012X

    Article  CAS  PubMed  Google Scholar 

  25. 25.

    Banerjee U, Izquierdo JA (1982) Antistress and antifatigue properties of Panax ginseng: comparison with piracetam. Acta Physiol Lat Am 32(4):277–285

    CAS  PubMed  Google Scholar 

  26. 26.

    Marasco CA, Ruiz VR, Villagomex SA, Infante BC (1996) Double-blind study of a multivitamin complex supplemented with ginseng extract. Drugs Exp Clin Res XXII 6:323–329

    Google Scholar 

  27. 27.

    Younus J, Collins A, Wang X, Saunders M, Manuel J, Freake C, Defen P (2003) A double blind placebo controlled pilot study to evaluate the effect of ginseng on fatigue and quality of life in adult chemo-naïve cancer patients. J Clin Oncol 22:733, abstract # 2947

    Google Scholar 

  28. 28.

    Asafu-Adjaye EB, Wong SK (2003) Determination of ginsenosides (ginseng saponins) in dry root powder from Panax ginseng, Panax quinquefolius, and selected commercial products by liquid chromatography: interlaboratory study. J AOAC Int 86(6):1112–1123

    CAS  PubMed  Google Scholar 

  29. 29.

    Wang X, Sakuma T, Asafu-Adjaye E, Shiu GK (1999) Determination of ginsenosides in plant extracts from Panax ginseng and Panax quinquefolius L. by LC/MS/MS. Anal Chem 8:1579–1584. doi:10.1021/ac980890p

    Article  Google Scholar 

  30. 30.

    Xie JT, Maleckar SA, Yuan CS (2003) Is ginseng free from adverse effects? In: Yuan CS, Bieber E (eds) Complementary and alternative medicine, chapter 17. CRC, Boca Raton

    Google Scholar 

  31. 31.

    Wang LC, Lee TF (1998) Effect of ginseng saponins on exercise performance in non-trained rats. Planta Med 64(2):130–133. doi:10.1055/s-2006-957389

    Article  CAS  PubMed  Google Scholar 

  32. 32.

    Vuksan V, Sievenpiper JL, Koo VY, Francis T, Beljan-Zdravkovic U, Xu Z, Vidgen E (2000) American ginseng (Panax quinquefolius L) reduces postprandial glycemia in nondiabetic subjects and subjects with type 2 diabetes mellitus. Arch Intern Med 160(7):1009–1013. doi:10.1001/archinte.160.7.1009

    Article  CAS  PubMed  Google Scholar 

  33. 33.

    Sotaniemi EA, Haapakoski E, Rautio A (1995) Ginseng therapy in non-insulin-dependent diabetic patients. Diabetes Care 18(10):1373–1375. doi:10.2337/diacare.18.10.1373

    Article  CAS  PubMed  Google Scholar 

  34. 34.

    King ML, Adler SR, Murphy LL (2006) Extraction-dependent effects of American ginseng (Panax quinquefolium) on human breast cancer cell proliferation and estrogen receptor activation. Integr Cancer Ther 5(3):236–243. doi:10.1177/1534735406291341

    Article  PubMed  Google Scholar 

  35. 35.

    King ML, Murphy LL (2007) American ginseng (Panax quinquefolius L.) extract alters mitogen-activated protein kinase cell signaling and inhibits proliferation of MCF-7 cells. J Exp Ther Oncol 6:147–155

    PubMed  Google Scholar 

  36. 36.

    Duda RB, Zhong Y, Navas V, Li MZ, Toy BR, Alavarez JG (1999) American ginseng and breast cancer therapeutic agents synergistically inhibit MCF-7 breast cancer cell growth. J Surg Oncol 72(4):230–239. doi:10.1002/(SICI) 1096-9098(199912) 72:4<230::AID-JSO9>3.0.CO;2-2

    Article  CAS  PubMed  Google Scholar 

  37. 37.

    Bahrke MS, Morgan WR (2000) Evaluation of the ergogenic properties of ginseng: an update. Sports Med 29(2):113–133. doi:10.2165/00007256-200029020-00004

    Article  CAS  PubMed  Google Scholar 

  38. 38.

    Ginseng Board of Wisconsin. http://www.ginsengboard.com. Last accessed November 2007

  39. 39.

    Mendoza TR, Wang XS, Cleeland CS, Morrissey M, Johnson BA, Wendt JK, Huber SL (1999) The rapid assessment of fatigue severity in cancer patient’s use of the Brief Fatigue Inventory. Cancer 85:1186–1196. doi:10.1002/(SICI) 1097-0142(19990301) 85:5<1186::AID-CNCR24>3.0.CO;2-N

    Article  CAS  PubMed  Google Scholar 

  40. 40.

    Ware JE, Sherbourne CD (1992) The MOS 36-Item Short-Form Health Survey (SF-36). Conceptual framework and item selection. Med Care 30(6):473–481. doi:10.1097/00005650-199206000-00002

    Article  PubMed  Google Scholar 

  41. 41.

    Buysse D, Reynolds C, Monk T, Berman S, Kupfer DJ (1989) The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 28(2):193–213. doi:10.1016/0165-1781(89)90047-4

    Article  CAS  PubMed  Google Scholar 

  42. 42.

    Guyatt GH, Osoba D, Wu AW, Wyrwich KW, Norman GR, Sloan JA, Clinical Significance Consensus Meeting Group (2002) Methods to explain the clinical significance of health status measures. Mayo Clin Proc 77:371–383. doi:10.4065/77.4.371

    Article  PubMed  Google Scholar 

  43. 43.

    Hyland ME, Sodergren SC (1996) Development of a new type of global quality of life scale and comparison and preference for 12 global scales. Qual Life Res 5(5):469–480. doi:10.1007/BF00540019

    Article  CAS  PubMed  Google Scholar 

  44. 44.

    Sloan A, O’Fallon JR, Suman VJ (1998) Incorporating quality of life measurement into oncology clinical trials. Proc Am Stat Assoc, pp 282–287

  45. 45.

    Wewers ME, Lowe NK (1990) A critical review of visual analogue scales in the measurement of clinical phenomena. Res Nurs Health 13:227–236. doi:10.1002/nur.4770130405

    Article  CAS  PubMed  Google Scholar 

  46. 46.

    Grunberg SM, Groshen S, Steingass S, Zaretsky S, Meyerowitz B (1996) Comparison of conditional quality of life terminology and visual analogue scale measurements. Qual Life Res 5:65–72. doi:10.1007/BF00435970

    Article  CAS  PubMed  Google Scholar 

  47. 47.

    Cohen J (1988) Statistical power analysis for the behavioral sciences. Erlbaum, Hillsdale, NJ

    Google Scholar 

  48. 48.

    Lipsitz SR, Fitzmaurice GM, Orav EJ, Laird NM (1994) Performance of generalized estimating equations in practical situations. Biometrics 50:270–278. doi:10.2307/2533218

    Article  CAS  PubMed  Google Scholar 

  49. 49.

    Sievenpiper JL, Arnason JT, Leiter LA, Vuksan V (2003) Variable effects of American ginseng: a batch of American ginseng (Panax quinquefolius L.) with a depressed ginsenoside profile does not affect postprandial glycemia. Eur J Clin Nutr 57(2):243–248. doi:10.1038/sj.ejcn.1601550

    Article  CAS  PubMed  Google Scholar 

  50. 50.

    Yuan C, Attele AS, Wu JA, Liu D (1998) Modulation of American ginseng on brainstem GABAergic effects in rats. J Ethnopharmacol 62:215–222. doi:10.1016/S0378-8741(98)00066-X

    Article  CAS  PubMed  Google Scholar 

  51. 51.

    Lian XY, Zhang Z, Stringer JL (2005) Protective effects of ginseng components in a rodent model of neurodegeneration. Ann Neurol 57(5):642–648. doi:10.1002/ana.20450

    Article  CAS  PubMed  Google Scholar 

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Author information

Affiliations

Authors

Corresponding author

Correspondence to Debra L. Barton.

Additional information

This study was conducted as a collaborative trial of the North Central Cancer Treatment Group and Mayo Clinic and was supported in part by Public Health Service grants CA-25224, CA-37404, CA-63849, CA-63848, CA-35267, CA-35431, CA-35269, CA-52352, CA-37417, CA-35415, CA-35103, CA-35119, CA-35195, CA-35448, CA-60276, CA-35101, CA-35113, CA-35103, and CA-35090.

Additional participating institutions include Iowa Oncology Research Association CCOP, Des Moines, IA 50314 (Roscoe F. Morton, M.D.); CentraCare Clinic, St. Cloud, MN 56301 (Harold E. Windschitl, M.D.); Sioux Community Cancer Consortium, Sioux Falls, SD 57105 (Loren K. Tschetter, M.D.); Siouxland Hematology–Oncology Associates, Sioux City, IA 51105 (Donald B. Wender, M.D.); Illinois Oncology Research Assn. CCOP, Peoria, IL 61615-7828 (John W. Kugler, M.D.); Montana Cancer Consortium, Billings, MT 59101 (Benjamin T. Marchello, M.D.); Meritcare Hospital CCOP, Fargo, ND 58122 (Preston D. Steen, M.D.); Toledo Community Hospital Oncology Program CCOP, Toledo, OH 43623 (Paul L. Schaefer, M.D.); Cancer Care Associates, Tulsa, OK 74136 (Mark R. Olsen, M.D.); Upstate Carolina CCOP, Spartanburg, SC 29303 (James D. Bearden, III, M.D.); Medical College of Georgia, Augusta, GA 30912 (Anand P. Jillella, M.D.); Geisinger Clinic & Medical Center CCOP, Danville, PA 17822 (Albert M. Bernath, Jr, M.D.); Mayo Clinic Jacksonville, Jacksonville, FL 32224 (Edith A. Perez, M.D.); Mayo Clinic Scottsdale, Scottsdale, AZ 85259-5404 (Tom R. Fitch, M.D.); Lehigh Valley Hospital, Allentown, PA 18103 (Suresh Nair, M.D.); and Hematology & Oncology of Dayton, Inc., Dayton, OH 45415 (Howard M. Gross, M.D.)

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Barton, D.L., Soori, G.S., Bauer, B.A. et al. Pilot study of Panax quinquefolius (American ginseng) to improve cancer-related fatigue: a randomized, double-blind, dose-finding evaluation: NCCTG trial N03CA. Support Care Cancer 18, 179 (2010). https://doi.org/10.1007/s00520-009-0642-2

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Keywords

  • Panax quinquefolius
  • American ginseng
  • Cancer-related fatigue
  • Botanicals