Frisk, J., Källström, A. C., Wall, N., Fredrikson, M., & Hammar, M. (2012). Acupuncture improves health-related quality-of-life (HRQoL) and sleep in women with breast cancer and hot flushes. Supportive Care in Cancer, 20, 715–724.
To evaluate the effectiveness of electroacupuncture (EA) and hormone therapy (HT) on health-related quality of life (HRQoL) and sleep in breast cancer survivors with vasomotor symptoms.
Women who had completed treatment for breast cancer were randomized to receive EA for 12 weeks or HT for 24 months. They completed the Psychological and General Wellbeing Index (PGWI) and Women’s Health Questionnaire (WHQ) pretreatment for vasomotor symptoms; during treatment; and at 6, 9, 12, 18, and 24 months after the start of treatment.
Women were excluded if they were receiving ongoing breast cancer treatment other than tamoxifen; had other malignancies; or had a history of thromboembolic, cereverbrovascular, or liver disease; porphyria; or active cardiovascular disease.
The study was a multicenter, randomized, prospective trial.
Nineteen women completed 12 weeks of EA. Eleven women were excluded due to changes in treatment. About 40% of the patients had no other treatment. The HT group had 11 women complete the 24 months of treatment. In both groups, reduction of hot flushes was noted. The EA group had a decrease in the median number of flushes/24 hours of 55% (p < 0.001) after 12 weeks. The decrease was 29% (p = 0.026) after 24 months. In the HT group, the median number of hot flushes/24 hours decreased by 100% (p = 0.001) after 12 weeks of treatment with no further changes. Sleep parameters improved significantly in both groups from baseline, with a WHQ sleep score in the EA group at baseline of 0.50 and at 24 months 0.33; in the HT group, the baseline score of 0.33 to declined 0.00 at 24 months.
The study showed improvement in sleep scores of both groups up to 21 months. The numbers of hours slept per night did not increase, but the numbers of flushes and distress caused by them decreased, resulting in fewer times woken, with overall improvement in HRQoL. Both groups also showed a significant decrease in the number of HF experienced, which was maintained up to 21 months after treatment was stopped.
EA, compared to HT for management of hot flashes in breast cancer survivors, shows some potential benefit in reducing numbers of hot flashes/24 hours, improving overall WHQ scores.
HT is not recommended as a safe treatment for vasomotor symptoms for breast cancer survivors. Thus, the value of using that group to compare with a group that received EA is of concern. EA needs further investigation in larger sample sizes. Further research is needed for efficacy of EA in hot flash management for breast cancer survivors and in women treated with aromatase inhibitors experiencing hot flash distress, as this study did not address that phenomenon.
Frisk, J. (2010). Managing hot flushes in men after prostate cancer--a systematic review. Maturitas, 65(1), 15-22.
To describe hot flushes in men with prostate cancer and their treatment methods.
TYPE OF STUDY Systematic review
DATABASES MEDLINE, ISI Web of Knowledge, Cinahl & PsycINFO
KEYWORDS Prostate cancer, androgen deprivation therapy, vasomotor symptoms, hot flashes treatment
INCLUSION CRITERIA All studies were randomized controlled studies (RCT) that addressed hot flashes (HF) in men with any stage of prostate cancer, treated with androgen deprivation therapy either medically or surgically. The studies addressed treatment for hot flashes where the main outcomes were frequency of hot flushes, distress from hot flushes, or hot flash score.
EXCLUSION CRITERIA Studies were limited to human studies and publications appearing between 1966 - 2009. Excluded were reviews & meta-analysis.
TOTAL REFERENCES RETRIEVED: 252
METHOD OF STUDY EVALUATION The Jadad score was used to assess the quality of the randomized controlled trial (RCT), on a five-point scale, and the QUORUM guidelines for systematic review were considered.
This summary did not include the measures that were used by the participants in reporting their hot flashes: i.e, diaries, skin temperature measurements, QOL surveys.
FINAL NUMBER STUDIED INCLUDED; N = 5 TOTAL SAMPLE SIZE: N = : 328 men were analyzed. SAMPLE RANGE ACROSS STUDIES : Sample sizes ranged from 12 - 177.
KEY SAMPLE CHARACTERISTICS: Samples included men with prostate cancer who had undergone surgical or medical castration and were currently experiencing hot flushes.
PHASE OF CARE Active Treatment
APPLICATIONS Late Effects and Survivorship; Elderly Care
In the five studies analyzed, the treatments that were studied included cyproterone acetate (CA), megestrol acetate (MA), gabapentin, transdermal clonidine, and diethylstilbestrol (DES). Unfortunately, none of the studies analyzed the same treatment. Because the studies looked at different interventions to relieve hot flushes (HF) in castrated men with prostate cancer, it was not possible to combine the studies to strengthen the outcomes. The studies' outcomes demonstrated varying degrees of success in relieving the hot flushes: Cyproterone acetate 100 mg, once per day, yielded 75% fewer HF than placebo (p<0.001), and 100% of men on CA had a 50% or greater reduction of mean number of HF, compared to placebo group. Megestrol acetate 20 mg, twice per day, yielded an 80% reduction of the median number of HF compared to a 19% reduction in the placebo group (p<0.001), an 87% reduction of median HF score vs. a 16% reduction for placebo (p<0.001), and a 50% or greater reduction of median number of HF (p<0.001) reported by 79% of MA group and 12% of placebo group. Gabapentin (4 schedules) achieved a 45.5% reduction of the median number of HF with 900mg gabapentin per day vs. 21.5% with placebo (p=0.02). Transdermal clonidine demonstrated no difference between the treated group and placebo. Diethylstilbestrol (1 mg) yielded a 100% reduction in the median number of HF vs.13% with placebo. 100% of DES and 14% of placebo reported a 50% or greater reduction of the median number of HF.
The systematic review of studies on treatment approaches to managing hot flushes in men after castration for prostate cancer showed very few such studies. Only five RCT studies were identified, and none of them analyzed the same treatment approach. Several of the studies that were presented demonstrated successful treatment approaches, including DES as the most effective, followed closely by MA and CA. However, these medications are linked to side effects that are not well tolerated by all patients.
Only five RCT studies were identified, and none of them analyzed the same treatment approach.
Large randomized placebo controlled studies are needed to clarify the data and provide clearer direction to managing HF in men who have been castrated as a treatment for prostate cancer. The summary, although providing insight for possible medical management, addressed only briefly the drop-out rates due to side effects. Further investigations of the drop-out subgroup could explore correlations among the medications to reveal unacceptable side effects in managing the participants’ hot flash symptoms. Further investigations comparing medications used and providing more specific information about measurements of QOL and hot flash reporting by participants are warranted.
Frisk, J., Carlhall, S., Kallstrom, A.C., Lindh-Astrand, L., Malmstrom, A., & Hammar, M. (2008). Long-term follow-up of acupuncture and hormone therapy on hot flushes in women with breast cancer: A prospective, randomized, controlled multicenter trial. Climacteric, 11, 166–174.
To evaluate the effects of electro-acupuncture (EA) and hormone therapy (HT) on vasomotor symptoms in women with a history of breast cancer
Twenty-seven women were randomized to EA for 12 weeks, 18 received HT for 24 months. The total population was 45.
This was an international, multicenter study, HABITS19, involving patients from three centers in Sweden between April 1998 and December 2002.
Randomized, controlled study
The patients were monitored with daily entries made in a log book, recording the numbers of hot flashes during day and night and how disturbing they were (range 0 for no distress to 10 for worst possible distress). The log books were completed daily for 1–3 weeks before treatment, continuously during the first 12 weeks of treatment, and thereafter for 1 week per month; altogether for 24 months. The measuring points were baseline, the 12th week of treatment, and at 1 week and 6, 9, 12, 18, and 24 months after start of treatment.
In 19 women who completed 12 weeks of EA, the median number of hot flashes per 24 hours decreased from 9.6 at baseline to 4.3 at 12 weeks of treatment. At 12 months after start of treatment, 14 women with only the initial 12 weeks of EA had a median number of flashes per 24 hours of 4.9, and at 24 months 7. Women with no other treatment than EA had 2.1 hot flashes per 24 hours.
Limitations included small sample size and relatively large attrition rate.
Freytes, C.O., Ratanatharathorn, V., Taylor, C., Abboud, C., Chesser, N., Restrepoo, A. et al. (2004). Phase I/II randomized trial evaluating the safety and clinical effects of repifermin administered to reduce mucositis in patients undergoing autologous hematopoietic stem cell transplantation. Clinical Cancer Research, 10, 8318-8324. PubMed Abstract
Repifermin (keratinocyte growth factor-2)
25 or 50 micrograms/kg
IV for 3 days prior to conditioning regimen and continued after transplant for up to 10 days.
Assessments before HSCT regimen, day of transplant, and 3x/wk until mucositis resolved.
The study was comprised of 42 patients (8 sites), with a mean age of 50.
21 each dose level – 14 study agent, 7 placebo
Auto HSCT
Multi-center
Randomized, double blind, placebo-controlled, phase I/II study
Effectiveness not established; study was not designed to have sufficient statistical power in identifying differences in efficacy between groups.
Number of end points suggest better outcome for 50 mcg group (mean duration, pain on swallowing, days on narcotic pain medication).
Number of post-transplant doses required was unclear.
Larger trial is needed.
Freyer, G., Jovenin, N., Yazbek, G., Villanueva, C., Hussain, A., Berthune, A., . . . Falandry, C. (2013). Granocyte-colony stimulating factor (G-CSF) has significant efficacy as secondary prophylaxis of chemotherapy-induced neutropenia in patients with solid tumors: Results of a prospective study. Anticancer Research, 33, 301–307.
To prevent the recurrence of neutropenic events (NEs) in patients with solid tumors and identify potential predictive factors of recurrence of NEs
The study was a prospective, multi-center, observational study to describe prophylactic strategies, including cycle delay, dose reduction, and granulocyte colony-stimulating factor (G-CSF), that were developed to prevent the recurrence of an NE subsequent to a previous episode in patients with solid tumors, and to evaluate their respective efficacy (primary endpoint). Secondary objectives assessed the recurrence rate of NEs and factors predictive of recurrence.
During cycle A, 16.1% experienced febrile neutropenia, 7.7% experienced neutropenic fever, and 76.3% experienced all-grade neutropenia. Cycle B was delayed in 44.5%, dose reductions occurred in 22.3%, and prophylactic G-CSF was given to 85% (59.7% received pegfilgrastim). The incidence of cycle delay and chemotherapy dose reduction decreased with further cycles of chemotherapy. The median number of G-CSF administrations with subsequent cycles, excluding pegfilgrastim, was five. The proportion of patients who experienced an NE was 29% when receiving G-CSF versus 68% for patients who did not. Only use of G-CSF was associated with a lower recurrence rate of febrile episodes (p < .001). In multivariate analysis, factors associated with a greater rate of NE occurrence were prior episode of febrile neutropenia, lung or colorectal cancer, metastatic disease, and prior radiotherapy.
Only the prophylactic administration of G-CSF was found to be an independent predictor of lower recurrence rate of NEs.
Teaching needs to be done related to G-CSF administration and the necessity of use. Further research is needed in G-CSF prophylaxis and the quality-of-life impact of other methods such as delay/dose reduction.
Freyer, G., You, B., Villet, S., Tartas, S., Fournel-Federico, C., Trillet-Lenoir, V., . . . Falandry, C. (2014). Open-label uncontrolled pilot study to evaluate complementary therapy with Ruta graveolens 9c in patients with advanced cancer. Homeopathy, 103, 232–238.
To investigate if Ruta graveolens 9c can improve quality of life and reduce tumor progression in patients with advanced disease.
Ruta graveloens is a medicinal plant that has been historically used to treat various inflammatory conditions Ruta graveloens was given at a 9c dilution in 1 ml ampules. The extract was taken orally twice daily for eight weeks. Patients continued treatment until there was tumor or clinical progression. Study data were obtained on day 1 and at weeks 8, 16, 28, 40, and 52. Examination and tumor markers were evaluated every four weeks.
Quality of life improved by week 8 (p < 0.001) and week 16 (p = 0.035). There were no significant changes in anxiety or depression scores. Mean duration of treatment was 3.3 months and median progression free survival was 1.9 months. Ninety percent had at least one adverse event, with an average of nine events per patient. Most comment symptoms were abdominal pain, fatigue, musculoskeletal pain, and headaches. None of the events were considered to be related to the study treatment.
Treatment with Ruta graveolens 9c did not have a demonstrable effect on anxiety or depression.
Ruta graveolens did not have an effect on anxiety or depression in this study.
Freye, E., Levy, J.V., & Braun, D. (2007). Effervescent morphine results in faster relief of breakthrough pain in patients compared to immediate release morphine sulfate tablet. Pain Practice, 7, 324–331.
To compare effervescent morphine to immediate release (IR) during breakthrough pain
Dosage adjustments of fixed schedule opioid could be made at the discretion of the investigator. Patients documented onset time, efficacy, and side effects of IR morphine given for breakthrough pain for one month. They were to take it within five minutes of breakthrough pain and titrate until sufficient relief, starting at 20 mg (equivalent to one effervescent tab). For the second month, the patients took effervescent morphine. They were instructed to take it within five minutes (they could take an additional one after 10 minutes) up to a max of four tabs for a single breakthrough pain episode. Patients could take non-investigational drugs for control of adverse effects (e.g., nausea, constipation, sedation). This was a long-term study that lasted up to six months.
During the IR morphine month, the mean VAS score was 8 and decreased to 3. During the effervescent morphine month, the mean VAS score of 7.8 decreased to 3.2. No statistically significant difference was seen between IR morphine and effervescent morphine; however, the difference was significant (p < 0.001) when comparing pain intensity prior to taking effervescent morphine. The time to relief with effervescent morphine was 13 minutes and 27 minutes with IR morphine (statistically significant, p < 0.001). Effervescent morphine decreased the number of breakthrough pain episodes from a mean of 3.3 per day to 2 per day. This was statistically significant (p < 0.01).
Although effervescent morphine had a faster onset, it does not compare with the onset of transmucosal fentanyl citrate (7–10 minutes).
Freitas, A.C., Campos, L., Brandao, T.B., Cristofaro, M., Eduardo Fde, P., Luiz, A.C., ... Simoes, A. (2014). Chemotherapy-induced oral mucositis: Effect of LED and laser phototherapy treatment protocols. Photomedicine and Laser Surgery, 32, 81–87.
A prospective study to compare the effect of an established laser therapy protocol with a potential therapy utilizing LED (light-emitting diode) on chemotherapy-induced oral mucositis
Both therapies analyzed in this study were efficient in preventing breaks in treatment.
LED phototherapy may be a viable alternative to traditional laser therapy to treat oral mucositis. This study, however, is small and has several flaws. Nurses should educate patients on proper oral hygiene to be used in combination with LED and laser therapy to promote optimal healing.
Freifeld, A.G., Bow, E.J., Sepkowitz, K.A., Boeckh, M.J., Ito, J.I., Mullen, C.A., . . . Wingard, J.R. (2011). Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clinical Infectious Diseases, 52, e56-e93.
To provide a guide for the use of antimicrobial agents for chemotherapy-induced fever and neutropenia in patients with cancer. The patient population targeted included adult and pediatric patients with neutropenia.
For this guideline document, the IDSA Standards and Practice Guidelines Committee reconvened many members of their original guideline panel, together with additional experts, in the management of patients with fever and neutropenia. The committee included experts in infectious diseases, oncology, and hematopoietic stem cell transplantation (HSCT) in both adult and pediatric patients. The literature was reviewed and graded according to a systematic weighting of the level and grade of the evidence for making a recommendation.
Patients were undergoing the active treatment phase of care.
Antibiotic Prophylaxis
Fluoroquinolone prophylaxis should be considered for high-risk neutropenic patients (patients expected to have absolute neutrophil counts (ANCs) of 100 cells/mm3 or lower for more than seven days. Levofloxacin and ciprofloxacin are the agents that have been evaluated the most and are generally equivalent, although levofloxacin is preferred for patients at risk for oral mucositis-related invasive viridans group streptococcal infection (B-1). The addition of a gram-positive active agent to fluoroquinolone prophylaxis is not recommended (A-1). Antibacterial prophylaxis is not indicated for low-risk patients anticipated to be neutropenic for less than seven days (A-III).
Antifungal Prophylaxis
Patients at high risk for candida infection, such as recipients of allogeneic HSCT and patients with acute leukemia undergoing intensive chemotherapy, should be treated with antifungal prophylaxis with fluconazole, itraconazole, voriconazole, posaconazole, micafungin, or caspofungin (A-I). Patients aged 13 years or older who are undergoing intensive chemotherapy for acute leukemia or myelodysplastic syndrome who are at high risk for aspergillus infection may be treated with posaconazole for antifungal prophylaxis (B-I). Prophylaxis against aspergillus infection is not effective in recipients of pre-engraftment HSCTs, but it is recommended for patients with a prior history of invasive aspergillosis (A-III), anticipated neutropenia of at least two weeks (C-III), or a prolonged period of neutropenia prior to transplantation (C-III). Antifungal prophylaxis is not recommended for patients with an anticipated duration of neutropenia of less than seven days (A-III).
Antiviral Prophylaxis
Herpes simplex virus–positive patients undergoing allogeneic HSCT or leukemia induction therapy should receive acyclovir antiviral prophylaxis (A-I). Annual influenza vaccination is recommended for all patients being treated for cancer (A-II). The optimal timing has not been established, but serologic responses may be best between chemotherapy cycles (more than seven days after the last treatment) or more than two weeks prior to the start of therapy (B-III).
Colony-Stimulating Factors
Colony-stimulating factors are recommended for prophylaxis against neutropenia when the anticipated risk of fever and neutropenia is 20% or greater.
Prevention of Catheter-Related Bloodstream Infections
Hand hygiene, maximal sterile barrier precautions, and cutaneous antisepsis with chlorhexidine are recommended for all central venous catheter insertions (A-I).
Hand Hygiene
Hand hygiene is the most effective means of preventing infection in the hospital (A-II).
Environment
HSCT recipients should be in private rooms (B-III). Patients with neutropenia do not need to be placed in single-patient rooms. Allogeneic HSCT recipients should be in rooms with more than 12 air exchanges, high-efficiency particulate absorption filtration, and positive pressure (A-III). Plants and dried or fresh flowers should not be allowed in the rooms of hospitalized neutropenic patients (B-III).
Isolation and Barrier Precautions
No specific protective gear (gowns, gloves, or masks) are necessary during the routine care of neutropenic patients. Standard barrier precautions should be used for all patients when contact with body fluids is anticipated.
Food
In general, food should be well cooked. Well-cleaned uncooked fruits and vegetables are acceptable.
Skin and Oral Care
Daily showers are recommended to maintain skin integrity (expert opinion). Patients should brush their teeth two times per day or more with a regular toothbrush, and flossing can be performed if it can be performed without trauma (expert opinion). Patients with mucositis should rinse their mouths with sterile water, saline, or sodium bicarbonate rinses four to six times per day (expert opinion). Menstruating immunocompromised women should avoid tampons (expert opinion). Rectal thermometers, enemas, suppositories, and rectal examinations are contraindicated for patients with neutropenia (expert opinion).
This was a comprehensive guideline developed by the Infectious Diseases Society of America (IDSA) to guide clinicians in the care of patients with chemotherapy-induced neutropenia and in the management of febrile neutropenia. The full guide can be located at http://cid.oxfordjournals.org/content/52/4/e56.full.
Freeman, L.W., White, R., Ratcliff, C.G., Sutton, S., Stewart, M., Palmer, J.L., . . . Cohen, L. (2014). A randomized trial comparing live and telemedicine deliveries of an imagery-based behavioral intervention for breast cancer survivors: Reducing symptoms and barriers to care. Psycho-Oncology. Advance online publication.
To determine the effects of guided imagery training on quality of life (QOL) for survivors of breast cancer
Trained professionals facilitated five weekly live (LD) or teleconference (TD) group sessions. The initial four sessions each included four one-hour modules of training in guided imagery (i.e., four hours per week). Each module was divided equally between a didactic lesson and an interactive small group activity. Didactic lessons provided education on the mind-body connection, particularly the influence of mental imagery and corresponding sensory experiences on physiologic processes. Small group activities incorporated opportunities to process lessons and to practice active and targeted imagery aimed at improving QOL. Each week, participants were given a guided imagery CD to reinforce current lessons and to promote the practice of imagery techniques daily. The fifth week provided a final group check-in for individuals to share their future plans for incorporating imagery into daily life. Weekly calls were made to encourage daily practice during the intervention and for three months postintervention. Waitlist controls (WLs) received no intervention. Outcome measures were assessed before the behavioral intervention and at one and three months after the intervention.
Randomized, waitlist-controlled trial
Both intervention groups (LD and TD) reported better cognitive function, less fatigue, and less sleep disturbance than waitlist controls (p < .01 for both). The LD and TD groups did not differ in any outcomes. No group effects were found for the other QOL outcomes. No time or group-by-time effects were found for any outcomes. A smaller portion of LD and TD participants reported clinically meaningful sleep disturbances (p < .01 for both) and fatigue (p < .05 for both) at the follow-up assessments.
After five weeks, the group guided imagery course provided by a trained facilitator may improve patient-reported cognitive impairment, sleep disturbances, and fatigue in breast cancer survivors. The delivery of this intervention in person or via teleconference produced the same results, suggesting that the intervention may be appropriate for use in telemedicine.
A group guided imagery course, delivered live or via teleconference by a trained facilitator, may improve cognitive impairment, sleep disturbance, and fatigue for breast cancer survivors. However, more research with larger samples and a longer follow-up is warranted to determine whether the intervention is effective and practical.