STUDY PURPOSE: To evaluate the efficacy of oral fentanyl combinations for breakthrough cancer-related pain

TYPE OF STUDY: Meta-analysis and systematic review

DATABASES USED: PubMed

KEYWORDS: breakthrough cancer pain; incident pain; pain flare; morphine; fentanyl

INCLUSION CRITERIA: RCT

EXCLUSION CRITERIA: Not specified

TOTAL REFERENCES RETRIEVED: Not stated

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Not stated

• FINAL NUMBER STUDIES INCLUDED = 5
• SAMPLE RANGE ACROSS STUDIES, TOTAL PATIENTS INCLUDED IN REVIEW: Not provided
• KEY SAMPLE CHARACTERISTICS: Not provided

APPLICATIONS: Palliative care

The probability of superior relief of breakthrough pain by differences in pain intensity scores at 15- and 60-minute intervals was calculated for immediate-release morphine and fentanyl preparations, versus placebo and versus each other. There was a 61% probability that morphine would produce a better outcome than placebo. Corresponding results versus placebo for fentanyl buccal tablet (FBT) was 97%, for orally disintegrating tablet (ODT) was 72%, and for transmucosal oral fentanyl (OTF) tablet was 81%. The probability of superiority of fentanyl over morphine during the first 60 minutes was 68% for FBT, 57% for ODT, and 66% for OTF. Pain intensity differences were larger for fentanyl preparations than for morphine when compared to placebo.

Findings suggest that oral fentanyl preparations may provide better relief of breakthrough pain during the first 60 minutes than immediate-release oral morphine.

• Small number of studies
• Only one study directly compared fentanyl preparations to morphine.

Findings suggest that oral fentanyl preparations may be more effective for management of breakthrough pain than oral immediate-release morphine. It should be noted however, that the duration of effect with morphine could be longer because of differences in half-life. Onset, intensity, and duration of relief of breakthrough pain with various approaches need to be evaluated to determine the best approach for individual patients.

To examine, within a blinded, randomized, controlled trial design, whether biofield therapy (hands-on healing) would significantly reduce fatigue in survivors with persistent cancer-related fatigue compared to mock healing and a wait-list control group.   

Energy chelation (hands-on-healing with standard hand positions focusing for five to seven minutes over each body part, i.e., feet, hips, knees, bladder, stomach, hands, elbows, shoulders, heart, throat, head, and heart) for one hour, two times each week for four weeks in the intervention group; mock biofield therapy for one hour, two times each week for four weeks; and a wait-list with no specific intervention. All participants submitted saliva samples at four time points. Timing of self-reported measures of quality of life (QOL) and depression were not reported.

• In total, 76 participants (100% female) with breast cancer were included. 
• Age ranged from 31 to 75 years. Mean age was 52 years in the healing group, 52 years in the mock group, and 50 years in the wait-list control group.
• Patients were included if they
  • Were aged 18 to 70 years
  • Were stage I to IIIA
  • Were one month to 10 years post completion of adjuvant or neoadjuvant therapy
  • Scored less than 50 on the RAND SF-36 vigor-fatigue subscale
  • Had no current use of biofield therapy.

• Single site  
• Outpatient
• University of San Diego, San Diego, California

• Patients were undergoing the long-term follow-up phase of care.
• The study has clinical applicability for late effects and survivorship.

The study used a blinded, randomized, controlled design.

• RAND SF-36 vigor-fatigue subscale    
• Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF)
• Center for Epidemiologic Studies Depression (CESD) Scale
• Functional Assessment of Cancer Therapy-Breast (FACT-B)
• Biofield Therapies Use and Expectations Questionnaire
   

• Overall attrition was 9%, with no differential attrition between groups. 
• No adverse events were reported.
• Previous use of biofield therapy was 49% prior to the study.
• The passage of time predicted changes for the overall sample for fatigue and QOL but not depression.
• There were no significant differences between biofield healing and mock healing on belief.
• Of the participants, 75% thought they received biofield healing.
• Compared with controls, biofield healing significantly decreased total fatigue (p < 0.0005; Cohen's d = 1.04), as did mock healing (p = 0.02; Cohen's d = 0.68), with no significant differences between biofield healing and mock healing.
• Cortisol slope significantly decreased for biofield healing versus both mock healing and control (p < 0.04 for both; Cohen's d = 0.58).
• Belief predicted changes in QOL over and above group (p = 0.004; Cohen's d = 0.84).
• Belief did not affect fatigue or cortisol variability.

Nonspecific factors are important in responses to biofield interventions for fatigue. Belief predicts QOL responses but not fatigue or cortisol variability. Biofield therapies increase cortisol variability independent of belief and other nonspecific factors. A need exists to further examine the effects of specific processes of biofield healing on outcomes for cancer populations.

• The study had a small sample size, with less than 100 participants.
• The study lacked follow-up assessment.
• The study lacked generalizability.
• Participants older than 70 years of age were included, which was determined to be an exclusion criterion.
   

Use of a hands-on healing intervention takes time and a skill set not traditionally taught in undergraduate or graduate nursing programs. Few clinical nurses have the time or skills to practice hands-on healing as described in the study. The intervention is noninvasive and a potentially effective independent nursing intervention with a minimal side effect profile.

To determine whether biofield therapies affect positive health outcomes and reduce disease symptoms.

Databases searched were PubMed, CINAHL, PyscINFO, and Allied and Complementary Medicine (AMED).

Search keywords were spiritual healing, subtle energy, energy healing, biofield healing, external qi therapy, emitted chi, emitted qi, qi therapy, Johrei, pranic healing, polarity therapy, Reiki, therapeutic touch, and healing touch. Investigators also manually searched the reference sections of studies and review papers.

Studies were included if they

• Were published in a peer-reviewed journal in the English language
• Used a proximally practiced (that is, practiced with the practitioner and client in the same room) biofield-based modality and included quantitative endpoints
• Were randomized, controlled trials (RCTs) with a within-subject design.

Studies were excluded if they related to distant healing or intercessory prayer; integrated modalities that were not biofield-based modalities with biofield-based modalities in such a way that the interventions could not be separated; were animal, plant, and/or in vitro studies; were clinical studies with group assignment but without randomization; were purely descriptive studies; or were unpublished dissertations.
 

• The number of references retrieved was 88.
• Investigators evaluated studies by means of an evaluation quorum that used a checklist of guidelines.
• Ten studies examined the outcomes associated with the use of biofield therapies for patients with cancer.
   

• The number of studies analyzed was 66.  
• The authors did not report the total sample size or the sample size range across studies.
• The sample included patients with pain; hospitalized and postoperative patients; and patients with dementia, cardiovascular issues, and cancer.
   

Patients were undergoing the active treatment phase of care.

The authors presented results according to type of patient and levels of evidence.

• Pain:  The analysis revealed Level I evidence to support biofield therapies as a means of reducing the intensity of pain; Level 4 evidence of affecting comprehensive pain assessment; and Level 4 evidence on affecting anxiety and depression. The analysis also revealed that biofield therapies could have positive effects on health-related quality of life.
• Cancer:  The analysis revealed Level 2 evidence to support biofield therapies as a means of reducing acute pain in patients with cancer; Level 4 of reducing chronic pain; Level 4 of affecting fatigue; Level 4 of affecting quality of life; and Level 4 of affecting physiological measures of relaxation response.
• Hospitalized and Postoperative Patients:  The analysis revealed Level 2 evidence to support biofield therapies as a means of reducing anxiety and Level 2 of reducing pain. The evidence that the analysis revealed about the effect of biofield therapies on depression and functional or autonomic outcomes was insufficient to allow conclusions.
• Dementia:  The analysis revealed Level 2 evidence to support biofield therapies as a means of reducing negative behavioral symptoms associated with dementia.
• Patients with Cardiovascular Issues:  The analysis revealed Level 4 evidence to support biofield therapies as a means of reducing anxiety and Level 4 of reducing diastolic blood pressure. Study quality and duration of each treatment session were not associated with the number of positive outcomes; however, the total number of treatment sessions was positively associated with the number of positive psychological outcomes.

Proximally practiced biofield therapies are promising complementary interventions as means of reducing pain intensity in multiple populations, reducing anxiety in hospitalized populations, and reducing agitated behaviors in patients with dementia. The long-term effects of the therapies on fatigue and autonomic nervous system activity are unclear.

• The review was systematic but not a meta-analysis.
• The authors relied on p-values versus effect size.
• Nonquantitative studies were not included.

Future research should compare biofield therapies with empirically supported treatments for specific conditions.

To compare the efficacy of multidose ondansetron with single-dose granisetron in complete emesis control and time spent in an ambulatory care setting in children with acute lymphoblastic leukemia (ALL) receiving moderately emetogenic cyclophosphamide-based chemotherapy

Eligible patients entered a four-week run-in period during which they were given antiemetic agents according to the randomization scheme before their scheduled IV cyclophosphamide chemotherapy. Regimens were either single-dose granisetron (0.5 mg for patients weighing 25–50 kg or 1 mg for patients over 50 kg) administered orally one hour before chemotherapy or three doses of ondansetron (0.15 mg/kg administered IV one hour before chemotherapy and again four hours after the first dose with an additional oral dose eight hours after the first dose). Parents were asked to keep a log of their child’s emetic episodes during the first 24 hours following chemotherapy. Antiemetic efficacy was assessed by the number of vomiting episodes, the need for rescue medication, and the extent of nausea and appetite loss.

• N = 33
• MEAN AGE = 7.8 years (SD = 4.9 years)
• MALES: 64%, FEMALES: 36%
• KEY DISEASE CHARACTERISTICS: Patients with ALL receiving IV cyclophosphamide
• OTHER KEY SAMPLE CHARACTERISTICS: Ages 3–18 greater than 25 kg; no pre-existing chronic nausea or vomiting; and no coadministration of corticosteroids

• SITE: Single site    
• SETTING TYPE: Outpatient    
• LOCATION: Taiwan

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Pediatrics

Single-institution, randomized, open-label, two-period crossover investigation

• Parents used a self-reported diary to document the number of emesis episodes.
• No other instruments or measurements were reported.
• No information was provided on how rescue medication, nausea, or appetite loss was measured.

In the granisetron arm, 20 out of 33 patients (60.6%) experienced complete efficacy compared to 15 out of 33 patients (45.5%) in the ondansetron arm, this was not statistically significant (p = 0.227). In both treatment groups, that males were less likely to respond to antiemetic treatment than females. In the granisetron group, 100% (12 out of 12) of females versus 76.2% (16 out of 21) of males experienced complete efficacy. In the ondansetron group, 100% (12 out of 12) of females versus 81% (17 out of 21) of males experienced complete efficacy. These differences did not meet a statistical significance (p = 0.271). The cost analysis demonstrated that granisetron costs about $0.20/kg (20 mcg/kg per patient), and ondansetron costs $20.09 per 8 mg vial or $6.18 per 4 mg tablet. This equates to about $0.99/kg (0.15 mg/kg per patient). The drug cost differential between the two modalities is $0.79/kg, favoring granisetron therapy on the basis of cost.

A single prophylactic oral dose of granisetron (10–20 mcg/kg) given prior to moderately emetogenic chemotherapy was at least as safe and effective as a triple dose of ondansetron given under similar circumstances. It also was more cost effective.

• Small sample (< 100)
• Risk of bias (no blinding)
• Measurement/methods not well described
• Measurement validity/reliability questionable 
• Findings not generalizable
• Other limitations/explanation: Subjects were followed for only 24 hours. Time spent in the clinic (a reported purpose of the study) was not reported in the findings. Conversely, cost was reported in detail in the results section but was not listed as a purpose of the study.

Based on this study, a single dose of oral granisetron (10–20 mcg/kg) is as safe and effective as a triple dose of ondansetron for moderately emetogenic chemotherapy in children with ALL in the acute phase of chemotherapy-induced nausea and vomiting only. There seems to be a gender difference in antiemetic efficacy.

To evaluate the symptoms and functional limitations of patients with secondary breast lymphedema following surgical treatment and to assess the additional therapeutic benefit of Deep Oscillation when combined with manual lymphatic drainage

Patients were randomized to the treatment group or the control group. The treatment group received 12 sessions of manual lymphatic drainage supplemented by Deep Oscillation, and the control group received manual lymphatic drainage alone.

• The study sample (N = 21) was comprised of a treatment group (n = 11) and a control group (n = 10) of female patients.
• Mean age for the treatment group was 56.6 years, with a range of 41–65 years and for the control group was 62.0 years, with a range of 42–71 years.
• All patients had breast-sparing surgery for breast cancer and were at least six weeks since their last irradiation.

The study took place at a single site in Berlin, Germany.

The study used a randomized controlled trial design.

• A 10-point visual analog scale was used to subjectively assess pain, breast swelling, and the effectiveness of lymphedema treatment.
• Range of motion of shoulder was measured using the neutral-zero method for passive range of motion.
• Range of motion of cervical spine was measured using the Zebris ultrasound-based movement sensor for active cervical spine mobility.
• ScanMobile served as a mobile 3D measuring system for the breast surface area in the target region.

Patients had high pain and swelling scores at baseline. Shoulder mobility was impaired in all patients; restriction of cervical spine mobility was common at baseline and declined further in the control group. Deep Oscillation resulted in significant pain reduction in the treatment group. The subjective reported reduction of swelling was confirmed objectively by 3D measurement only in the treatment group.

Additional Deep Oscillation supplementary to manual lymphatic drainage can enhance pain alleviation and swelling reduction.

• The study sample was small, with less than 30 patients.
• Placebo effect may exist because of the use of a new technique.
• The number of treatment sessions per week was higher in the treatment group with two to three sessions per week compared to control group with only one to two sessions per week.

More attention should be paid to patients with breast lymphedema. Treatment with low-intensity and extremely low-frequency electrostatic fields could be a useful supplementary therapy in the management of patients with breast lymphedema. However, more studies with larger sample sizes are needed to duplicate the findings from this study.

To evaluate a multi-modular self-care program, Self-Care Improvement through Oncology Nursing (SCION), consisting of emesis treatment, nutritional support, counseling, and relaxation interventions to reduce anorexia, nausea, and emesis (ANE)

Patients were randomized to receive either standard care (control) or the SCION program, which included four modular, algorithm-based protocols. In the intervention group, all patients received Module 1, \"Information leaflet,\" and Module 2, \"Structured consultation,\" at various times during treatment. Module 3 “Nutrition counseling” and Module 4 “Relaxation” were given if a patient developed significant nausea, emesis, or weight loss. Patients in the control group received set emesis prophylaxis. Assessments were made on days 1–5 of two chemotherapy cycles and day 8 of the second cycle.

• The study consisted of 208 participants.
• Mean age in the control group was 53.38 years (SD = 13.69 years). Mean age in the intervention group was 50.52 years (SD = 13.21 years).
• In the control group, 48% of the sample was female. In the intervention group, 71.4% of the sample was female.
• Diagnoses were gynecologic (47%), urologic (5%), hematologic (16%), other (32%).
• In the control group, 40% of patients were receiving chemotherapy with level 4 emetogenic potential and 60% were receiving chemotherapy with level 5 emetogenic potential. In the intervention group, 22% were receiving level 4 emetogenic potential and 78% were receiving level 5 emetogenic potential.
• In the control group, 11% of patients were receiving NK1 receptor antagonists (RAs) in addition to 5-HT₃ RAs and steroids. In the intervention group, 20% were receiving NK1 RAs in addition to 5-HT₃ RAs and steroids.

The study was conducted in inpatient and outpatient settings at two German university hospitals.

All patients were in active treatment.

This was a randomized, controlled study.

• All patients were assessed on days 1-5 of two chemotherapy cycles for nausea, vomiting, anorexia, and weight loss using Common Terminology Criteria for Adverse Events, version 3.0 (CTCAE v3.0).
• A summative score was used to bring each symptom to a 0-10 range; formula: ANE = 2.5 x (anorexia, nausea, vomiting) + 3.33 x weight loss.
• A 100-mm visual analog scale (VAS), ranging from insufficient to very good, was used to capture patient knowledge of chemotherapy-related side effects and effective self-care activities
• The Appraisal of Self-Care Agency (ASA-A) scale was used to assess self-care agency.
• The Self-Care Chemotherapy Side Effect Questionnaire was used to assess self-care activities.
• Quality of life was assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ).

• No significant differences were found between the intervention and control groups in the reduction of ANE or chemotherapy side effect knowledge, self-care activities, or efficacy of competence activities.
• Quality of life (QOL) was significantly better in the control group (p = 0.017).
• Interactions between ANE intensity and the covariates were not statistically significant.
• Nausea (46%) was reported as the most frequent side effect.

The initial hypothesis, that a structured intervention for patients receiving chemotherapy with moderate or high emetogenic potential would significantly decrease ANE intensity, was not supported. The effectiveness of the nursing intervention to reduce chemotherapy-induced ANE and increase QOL could not be supported. Rather, the intervention was reported to have a negative effect on QOL.

• No appropriate control group was included.
• A 16% dropout rate occurred in the intervention group, because of imbalances in randomization (a higher number patients with hematologic cancers with additional radiotherapies).
• No evidence of standardized teaching or written materials was provided.
• A potential for bias existed because the nurses who administered the intervention and assessed the outcomes were aware of group allocation.
• Descriptions of the validity and reliability of the measurement tool were poor.
• The results did not reflect whether the program was effective or if effectiveness was a result of low ANE incidence and intensity.

The SCION program had no effect in reducing distressing ANE.

To evaluate Self Care Improvement through Oncology Nursing (SCION-PAIN), a nursing-administered program to reduce patients’ barriers and improve pain management and pain-related discharge management

The intervention was a nurse-led counseling program to improve pain management and pain-related discharge management by reducing patient-related cognitive barriers. In the intervention group, the SCION-PAIN program was administered by specially trained ward nurses in cooperation with a study nurse. Initial education was standardized, and follow-up was tailored to individual needs. Three initial sessions were provided during hospital stay, and a follow-up telephone counseling session was done two to three days after discharge. Study measures were obtained at baseline, at discharge, and on days 7, 14, and 28 after discharge.

• N = 202  
• AVERAGE AGE = 55.9 years (control); 57.75 years (intervention)
• MALES: 60 (57.1%) control; 59 (57.8%) intervention, FEMALES: 45 (42.9%) control; 43 (42.2%) intervention
• KEY DISEASE CHARACTERISTICS: Gynecologic tumors 21/105 (20%) control and 20/101 (19.8%) intervention; urologic tumors 4/105 (3.8%) control and 12/101 (11.9%) intervention; hematologic malignancies 15/105 (14.3%) control and 1/101 (1%) intervention; gastrointestinal tumors 26/105 (24.8%) control and 40/101 (39.6%) intervention; other tumors 39/105 (37.1%) control and 28/101 (27.7%) intervention

• SITE: Multi-site  
• SETTING TYPE: Multiple settings (inpatient and home setting)
• LOCATION: Eighteen oncology wards from two German university hospitals

• PHASE OF CARE: Active antitumor treatment

Cluster-randomized trial

• The effectiveness of the SCION-PAIN program was assessed by the difference in patient-related barriers to the management of cancer pain between the control and intervention groups using the Barriers Questionnaire II.
• Secondary endpoints were measured with the Brief Pain Inventory (BPI), the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ), the German Pain Coping Questionnaire (GPCQ), and the Medication Adherence Scale (MAS).
• Health-related quality of life was measured by the EORTC-QLQ C30.

Compared to usual care, the SCION-PAIN program reduced cognitive barriers in cancer pain management more effectively (p < 0.02), and patients who participated in this program showed a significant increase in perceived knowledge of cancer pain. There was no difference between the groups in average or worst pain intensity. Patients in the intervention group adhered better to pain medications (p = 0.02).

The results of this study demonstrated the effectiveness of the SCION-PAIN program as a brief, easily administered, nurse-led intervention to improve the self-management of pain in patients with cancer. Patient education could help to empower patients to actively participate in their pain treatment and develop self-management skills, improving adherence through care transitions. Participants in the program demonstrated a lower intensity of pain.

• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Findings not generalizable
• Intervention expensive, impractical, or training needs
• Subject withdrawals ≥ 10%
• Other limitations/explanation: Small number of randomized clusters; effects caused by differing personalities of the included participants; the responses to the information provision, different levels of social support, or of mental resilience were not assessed systematically

The results of this study emphasized the integral role of nurses as part of the supportive or palliative care team. This study also confirmed that the inpatient period provides a very valuable and suitable timeframe to improve patients’ self-management and communication skills to prepare them for care transitions.

To evaluate the efficacy of selenium intake for prevention of oral mucositis (OM) in patients with hematologic malignancies who are candidates for allogeneic hematopoietic stem cell transplantation (HSCT) after receiving high-dose chemotherapy (HDC)

Patients randomly were assigned to the selenium or control group in a blocked, randomization schedule. They were given either a selenium tablet (200 mcg) or placebo tablet twice daily, from the starting day of HDC to 14 days after transplantation. Chemotherapy was the same for all patients. All patients received a similar regimen for prevention of mucositis, including nystatin, sucralfate, and mouthwashes with chlorhexidine, plus 10 cc diluted povidone-iodine every three hours. Narcotic analgesics rarely were used to alleviate OM.

• N = 77 patients participated, 74 patients completed, and 3 patients discontinued
• MEAN AGE = 33.3 years
• MEDIAN AGE: 32 years
• RANGE: 18–55 years
• MALES: 56%, FEMALES: 44%
• KEY DISEASE CHARACTERISTICS: Acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL)
• OTHER KEY SAMPLE CHARACTERISTICS: Disease status before transplant was evenly matched in the study and control group.

• SITE: Hematology-Oncology and Stem Cell Transplantation Research Center    
• SETTING TYPE: Shariati Hospital  
• LOCATION: Tehran, Iran

• PHASE OF CARE: Treatment
• APPLICATIONS: Adult patients with AML or ALL undergoing allogeneic HSCT

• Double-blind, randomized, controlled study

• Five-grade World Health Organization (WHO) toxicity scale for OM
  • Assessment was carried out by one author under the supervision of the attending physician; both were blinded to patients’ allocation.
  • Assessed on a daily basis (except for weekends and holidays)
  • Assessed from day one of HDC until 21 days after transplantation, or until OM was resolved

The cumulative incidence of OM (WHO scale grades of 1–4) in the selenium group and control group was not significantly different. The incidence of severe OM (grades 3 and 4) was significantly lower in the selenium group (10.8% versus 35.1%, P = 0.013). Two patients in the control group experienced WHO OM grade 4, and none of the patients in the selenium group experienced grade 4. Mean duration of OM was not different between the two groups. Mean duration of OM from the beginning of grade 2, moving up to grade 4, and then returning to grade 2 was significantly lower in the selenium group. No difference was seen in the start day of OM between the two groups.

Selenium supplementation during HDC may prevent severe OM in patients undergoing allogeneic HSCT. Further testing is needed before selenium can be recommended. Further testing is needed to establish optimal dose, time to initiate, and duration of treatment with selenium.

• Small sample: < 100
• Single institution
• No mention of how the outcome assessor was trained to do the assessments
• Authors contradicted themselves when they stated no patients in the selenium group experienced grade 4 OM, yet also stated in the results that mean duration from beginning of grade 2, moving up to grade 4, and returning to grade 2 was significantly lower in the selenium group.

Nurses need to be informed about possible effective methods for reducing and eliminating OM to guide their patients.

Prophylactic laser treatment was administered daily from beginning of conditioning regimen to two days after stem cell transplantation.

Patients received gallium aluminum arsenate diode laser therapy on four anatomic sites of the oral mucosa.

660 nm 10 mW 2.5 J/cm² was administered. Each anatomic site was illuminated for 10 seconds per point.

 

Patients with HSCT from Brazil aged 17-62 years

Historical control group (1999–2000): n = 25

Laser group: n = 24
 

The study occurred from January 2003-September 2004.

WHO

Administration of morphine

Time of parenteral nutrition
 

Incidence of mucositis was the same in both groups.

Percentage of grade 2, 3, and 4 mucositis was less in laser group, not SS (p = 0.12). The laser group took longer to develop grade 1 (4.36 versus 6.12 days [p = 0.01], had fewer days of pain (5.64 versus 2.45 [p = 0.04], and had fewer patients who required morphine (10 versus 4 [p = 0.07].
 

Limited sample size and methodology

Number of patients with grade 3–4 may have been SS with larger sample.
 

 To assess the effect of black cohosh on the frequency and intensity of hot flashes in survivors of breast cancer

The study explored the use of black cohosh for treatment of hot flashes among women with a history of breast cancer. The black cohosh and placebo were supplied by the manufacturer. Each participant received 130 tablets and took one tablet twice daily with meals for 60 days.

• Eighty-five participants were enrolled  (59 on tamoxifen, 26 not on tamoxifen); 42 participants were assigned to treatment; 43 were assigned to placebo; 69 completed all three hot flash diaries.
• Inclusion criteria: Participants had to have completed primary therapy, including chemotherapy and radiation therapy, at least two months before entering the trial.
• Exclusion criteria: Patients could not be using hormonal replacement therapy for hot flashes, be pregnant, have major psychiatric illness, or have recurrent or metastatic breast cancer.
• Participants were stratified based on if they used tamoxifen.

The study was a randomized clinical trial: two-arm randomization, double-blind, placebo-controlled.

Participants were asked to record in a diary the number of hot flashes and the intensity of each. Participants scored severity as 1 = mild, 2 = moderate, and 3 = severe, for three days before starting to take any study pills, then again on days 27 to 30, and on days 57 to 60. FSH and LH levels were measured in a subset of participants at the first and final visits.

Sample size was chosen for 90% power to detect a 30% difference between groups in mean numbers of hot flashes, with a SD of 4.0. All analyses were stratified by tamoxifen use. The primary efficacy end point was mean numbers of hot flashes at 57 to 60 days. The safety end points were changes in mean levels of FSH and LH at the start and end of study participation associated with treatment. In hot flash intensity, both groups experienced a decline during the first month of study participation. The differences between groups in intensity at the end of the study were not significant. For the overall hot flash activity score, the differences between the treatment and placebo groups adjusted for tamoxifen were not statistically significant. Changes in FSH and LH levels of also did not differ between the two groups.

Data provide little evidence of either harm or benefit from using black cohosh to control hot flashes.

A limitation of this study is that participation lasted only two months.