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- Ashwagandha (Withania somnifera)
- Chemotherapy-induced Fatigue
- Breast Cancer
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Date:
06-14-2013 | HC# 021366-474
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Re: Adjunct Treatment with Ashwagandha Root Extract for Fatigue from Chemotherapy for Breast Cancer
Biswal
BM, Sulaiman SA, Ismail HC, Zakaria H, Musa KI. Effect of Withania somnifera (ashwagandha) on the development of
chemotherapy-induced fatigue and quality of life in breast cancer patients. Integr Cancer Ther. November 2012; [epub
ahead of print]. doi: 10.1177/1534735412464551.
Breast
cancer is a common form of cancer in women; 1 in 8 women in North America
develop breast cancer. Breast cancer is treated with surgery, radiotherapy, and
chemotherapy, with chemotherapy drugs administered in combination and given in
cycles. Among the many adverse side effects of this regimen is fatigue that is not
alleviated by resting. Fatigue may be treated by exercise and psychotherapy,
along with yoga, psychostimulants with adverse effects (e.g., methylphenidate),
and other conventional treatments. The traditional Ayurvedic medicinal plant
ashwagandha (Withania somnifera) has
been shown to have antitumor, antidepressant, and memory- and
cognitive-enhancing bioactivity; however, there have been few clinical trials to
study this botanical. This open-label, prospective, non-randomized, comparative
clinical trial investigated the potential of ashwagandha use for the
alleviation of fatigue from chemotherapy and for improving the quality of life
(QoL) in patients with breast cancer.
Patients
with stage I-IV breast cancer, an Eastern Cooperative Oncology Group (ECOG)
performance rating of 0 to 2 (a scale assessing the overall health of patients
with cancer, where 0=full activity and 5=death), and who were candidates for
chemotherapy were enrolled in the study and placed alternately in either the study
or control groups. Those that had prior chemotherapy or radiation treatment; were
taking psychiatric drugs; or had other mental or systemic illnesses were
excluded.
Prior
to each chemotherapy cycle, blood counts and liver and kidney functional
assessments were taken. The ECOG performance rating was taken at baseline, as
well as scores for the fatigue assessment tools (the Piper Fatigue Scale [PFS],
Schwartz Cancer Fatigue Scale [SCFS-6], and the QoL measurement for patients with
cancer, known as the European Organization for Research and Treatment of Cancer
Quality of Life Questionnaire C30 [EORTC QLQ-C30]). PFS scores were also taken
during the initial day of the first, third, and sixth chemotherapy cycles; and
SCFS-6 and EORTC QLQ-C30 scores were measured on the initial day of all 6
cycles.
Chemotherapy
treatments were either a combination of cyclophosphamide, epirubicin, and 5-fluorouracil
(CEF) or Taxotere®, Adriamycin®, and cyclophosphamide
(TAC). Treatments were given intravenously every 3 weeks. Patients also took
ondansetron or granisetron for nausea. Patients taking the TAC combination also
took granulocyte colony-stimulating factor (G-CSF) therapeutics to alleviate the
lessening of white blood cells.
Ashwagandha
root extract powder was supplied by Himalaya Drug Co.; New Delhi, India. Each
capsule held 500 mg; patients consumed 4 capsules 3 times per day with water,
during 6 cycles of chemotherapy treatments. Some patients needed to split the dosage
further throughout the day due to difficulty swallowing or gastric upset, but the
total daily dosage was kept constant.
In
total, the study group consisted of 50 patients who had an average age of 51
years; and the control group was made up of 50 patients who had an average age
of 50.5 years. Estrogen receptor-positive (ER+) cancer was present in 54% of
the study group and 56% of the control group. In addition, 48% of the study
group had progesterone receptor-positive (PR+) cancer, while 50% of the control
group had this form of cancer. Also, 26% of patients in the study group had
cancer overexpressing human epidermal growth factor receptor 2 (HER2), while
this was observed in 52% of patients in the control group. Stage II and III
cancers were present in 80% of the study group versus 76% of the control group.
For 72% of the study group, surgery was done as the initial therapy, while 78%
of the control group had surgery first. Radiation treatment was given to 90% of
those in the study group and to 88% in the control group. The TAC regimen was
employed with 50% of the study group and 70% of the control group. Of the total
patients, 44 patients finished all chemotherapy cycles in the study group, while
41 patients finished in the control group. Reasons for some of the dropouts included
voluntary withdrawal and deaths unrelated to the study. The remaining patient
dropouts are not accounted for or explained.
The
SCFS-6 fatigue mean score across the study was significantly higher in the
control group as compared to the study group (P<0.003). Also, the PFS mean
scores were significantly higher in the control group than in the study group
(P<0.001). Lower scores indicate less fatigue in both of these assessments.
The mean scores of the EORTC QLQ-C30 were also significantly less in the study
group for the categories of fatigue, insomnia, appetite loss, constipation,
financial difficulties, and pain, as compared to the control group (P<0.001
to P=0.024), indicating a lesser degree of symptoms. The scores for the
categories of physical functioning, role functioning, emotional functioning, social
functioning, and global health status/QoL were significantly greater in the
study group as compared to the control group (P<0.001 to P<0.001). Compliance
with ashwagandha treatment was 98%; and patient complaints included "oral
intolerance," gastritis, and flatulence.
In
summary, those patients with cancer who were taking ashwagandha had lower
degrees of fatigue and a higher QoL during chemotherapy than the patients in
the control group. Ashwagandha may prove to be a beneficial adjunct treatment like
other standard therapeutics for fatigue, such as exercise, in those undergoing
chemotherapy. Although not addressed in this study, previous preclinical
research suggests that there are limited herb-drug interactions between ashwagandha
and chemotherapy regimens that enhance drug efficacy and/or reduce adverse
effects, pointing to the safety of this botanical for use in patients with
cancer; this needs future confirmation.
Limitations
discussed include using 2 forms of chemotherapy treatment instead of just one; enrolling
patients suffering from the later stages of cancer progression; and the limited
sample size. In addition, this study would have benefitted from more specific
data analysis. For example, baseline and endpoint comparisons would have been
helpful, and information regarding patient dropouts and the adverse side
effects in the control group is missing. Also, the results of the liver and
kidney functional assessments at the study's end are not mentioned, making it
difficult to draw conclusions about the safety of ashwagandha. Finally, failure
to adequately characterize the ashwagandha root extract used, aside from noting
its manufacturer, makes extrapolation of the results impractical. In
conclusion, more detailed studies are necessary to confirm the use of this
botanical in relation to breast cancer treatment.
—Amy C. Keller,
PhD
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