Purpose: Patients undergoing treatment for cancer often report problems with their cognitive function, which is an essential component of health-related quality of life. Pursuant to this, a two-arm randomized, placebo-controlled, double-blind, phase III clinical trial was conducted to evaluate Ginkgo biloba (EGB 761) for the prevention of chemotherapy-related cognitive dysfunction in patients with breast cancer. Methods: Previously chemotherapy naïve women about to receive adjuvant chemotherapy for breast cancer were randomized to receive 60 mg of EGB 761 or a matching placebo twice daily. The study agent was to begin before their second∈cycle of chemotherapy and to be taken throughout chemotherapy and 1 month beyond completion. The primary measure for cognitive function was the High Sensitivity Cognitive Screen (HSCS), with a secondary measure being the Trail Making Tests (TMT) A and B. Subjective assessment of cognitive function was evaluated by the cognitive subscale of the Perceived Health Scale (PHS) and the Profile of Mood States (POMS). Data were collected at baseline and at intervals throughout and after chemotherapy, up to 24 months after completion of adjuvant treatment. The primary statistical analysis included normalized area under the curve (AUC) comparisons of the HSCS, between the arms. Secondary analyses included evaluation of the other measures of cognition as well as correlational analyses between self-report and cognitive testing. Results: One hundred and sixty-six women provided evaluable data. There were no significant differences in AUC up to 12 months on the HSCS between arms at the end of chemotherapy or at any other time point after adjuvant treatment. There were also no significant differences in TMT A or B at any data point. Perceived cognitive functions, as measured by the PHS and confusion/bewilderment subscale of the POMS, were not different between arms at the end of chemotherapy. There was also little correlation between self-reported cognition and cognitive testing. No differences were observed in toxicities per Common Terminology Criteria for Adverse Events (CTCAE) assessment between Ginkgo biloba and placebo throughout the study; however, after chemotherapy, the placebo group reported worse nausea (p∈=∈.05). Conclusion: This study did not provide any support for the notion that Ginkgo biloba, at a dose of 60 mg twice a day, can help prevent cognitive changes from chemotherapy. These analyses do provide data to further support the low associations between patients' self-report of cognition and cognitive performance, based on more formal testing.
Bibliographical noteFunding Information:
Acknowledgments 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-35195, CA-35431, CA-35269, CA-35101, CA-63848, CA-37417, CA-35415, CA-35448, CA-35103, CA-35119, CA-35103, and CA-35272. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. Additional participating institutions include: Siouxland Hematology-Oncology Associates, Sioux City, IA 51105, USA (Donald Wender, M.D.); Toledo Community Hospital Oncology Program (Paul L. Schaefer, M.D.); Medical College of Georgia, Augusta, GA 30912, USA (Anand P. Jillella M.D.); Iowa Oncology Research Association CCOP, Des Moines, IA 50309, USA (Robert J. Behrens, M.D.); Rapid City Regional Hospital, Inc., Rapid City, SD 57701, USA (Richard Charles Tenglin, M.D.); Columbus CCOP, Columbus, OH 53215, USA (J. Philip Kuebler, M.D., Ph.D.); Mayo Clinic Florida, Jacksonville, FL 32224, USA (Kurt A. Jaeckle, M.D.); Michigan Cancer Research Consortium, Ann Arbor, MI 48106, USA (Philip J. Stella, M.D.); Meritcare Hospital CCOP, Fargo, ND 58122, USA (Preston D. Steen, M.D.); Gei-singer Clinic & Medical Center CCOP, Danville, PA 17822,USA (Albert M. Bernath, Jr, M.D.); Upstate Carolina CCOP, Spartanburg, SC 29303, USA (James D. Bearden, III, M.D.); Montana Cancer Consortium CCOP, Billings, MT 59101, USA (Benjamin T. Marchello, M.D.); Sioux Community Cancer Consortium, Sioux Falls, SD 57105, USA (Miroslaw Muzurczak, M.D.); Lehigh Valley Hospital, Allentown, PA 18103, USA (Suresh Nair, M.D.); Ochsner CCOP, New Orleans, LA 70121, USA (Jyotsna Fuloria, M.D.); Colorado Cancer Research Program, Denver, CO 80224, USA (Eduardo R. Pajon, Jr., M.D.).
- Adjuvant treatment
- Breast cancer
- Chemotherapy-related cognitive dysfunction
- Dietary supplements
- Ginkgo biloba