Loprinzi, C.L., Michalak, J.C., Quella, S.K., O’Fallon, J.R., Hatfield, A.K., Nelimark, R.A., … Oesterling, J.E. (1994). Megestrol acetate for the prevention of hot flashes. New England Journal of Medicine, 331, 347–352.
The study was done to assess the efficacy and short-term toxicity of low-dose megestrol acetate as a treatment for hot flashes in women with breast cancer and in men who had undergone androgen-deprivation therapy for prostate cancer.
Subjects were randomly assigned to receive megestrol 20 mg twice a day for 4 weeks followed by placebo for 4 weeks.or placebo for 4 weeks then megestrol for 4 weeks. Subjects received no medication for the first 7 days.
Of the enrolled subjects, 163 cpmpleted the study. They included women with a history of breast cancer and men who had undergone surgical or medical orchiectomy. All had at least one hot flash per month. Women were stratified according to duration of hot flashes (9 months cut point). Men were stratified by medical or surgical orchiectomy and duration of androgen ablation.
The study was a double-blind, randomized, crossover trial.
Participants kept hot flash diaries, recording the number and severity of hot flashes each day. They also recorded appetite changes, fluid retention, and vaginal problems.
During the first 4 week medication period, megestrol was associated with decreased frequency of hot flashes for both men and women. Crossover analysis was not performed because of carryover effects of medication.
There was an insufficient washout period to allow for crossover analysis.
Loprinzi, C.L., Sloan, J., Stearns, V., Slack, R., Iyengar, M., Diekmann, B., … Novotny, P. (2009). Newer antidepressants and gabapentin for hot flashes: An individual patient pooled analysis. Journal of Clinical Oncology, 27, 2831–2837.
Efficacy and side-effects of three relatively low gabapentin doses in comparison to placebo.
Randomized to:
Outpatient oncology centers
Double-blind, placebo-controlled.
Hot flash frequencies and severities were recorded daily for a baseline week and for four weeks while taking the study medication; symptom experience diaries were completed weekly for five weeks; 30-item Profile of Mood States–Brief was completed at the end of the baseline week and the end of four weeks of treatment.
By the fourth treatment week, mean hot flash scores decreased from baseline in the placebo group by 4.1 units. They also decreased in the three increasing dose gabapentin groups by 3.2, 4.6, and 7.0 units. No significant difference was reported in the three combined gabapentin arms versus placebo: Wilcoxon rank-sum p values for change in hot flash scores and frequencies after four weeks of treatment were 0.10 and 0.02 comparing the highest dose gabapentin arm to the placebo arm, respectively.
Short follow-up period
Loprinzi, C. L., Kugler, J. W., Barton, D. L., Dueck, A. C., Tschetter, L. K., Nelimark, R. A., . . . Jaslowski, A. J. (2007). Phase III trial of gabapentin alone or in conjunction with an antidepressant in the management of hot flashes in women who have inadequate control with an antidepressant alone: NCCTG N03C5. Journal of Clinical Oncology, 25, 308-312.
To determine the effectiveness of Gabapentin in combination with an antidepressant for the treatment of hot flashes.
Women must have been on a stable dose of antidepressant for the tx of hot flashes. In week one, patients completed a hot flash diary. In the second week, patients took 300 mg gabapentin at bedtime for 3 days, then twice daily for 3 days, then 3 times a day for 22 days. In one arm of the study patients remained on their previous dose of antidepressant and in the other arm patients weaned off antidepressants over 7-10 days and physician discretion was allowed. Patients completed a daily hot flash diary for 4 week and a weekly symptom assessment.
SITE Single site SETTING TYPE Outpatient LOCATION USA
PHASE OF CARE Late effects and survivorship
RCT
Both groups experienced a reduction in hot flashes: gabapentin = 60% reduction (95% CI, 33%-73%) and gabapentin plus antidepressant = 56% reduction (95% CI, 26%-71%)No difference between groups in hot flash scores or frequency from baseline to 4 weeks in either arm. No difference in toxicities reported by either arm. No difference in QOL in either arm.
This trial failed to demonstrate that the combination of gabapentin with antidepressants is more effective to reduce the number of hot flashes experienced by breast cancer survivors.
Risk of bias (no control group)
Risk of bias (no blinding)
Risk of bias(sample characteristics)
Other limitations/*explanation All breast cancer patients, no placebo arm
The combination of gabapentin plus antidepressant does not appear to be an effective regimen to decrease hot flashes in breast cancer survivors
Loprinzi, C.L., Sloan, J.A., Perez, E.A., Quella, S.K., Stella, P.J., Mailliard, J.A., … Rummans, T.A. (2002). Phase III evaluation of fluoxetine for treatment of hot flashes. Journal of Clinical Oncology, 20, 1578–1583.
The study sought to assess the efficacy of fluoxetine for treatment of hot flashes in women with a history of breast cancer or a concern regarding the use of estrogen because of a breast cancer risk.
Patients received four weeks of fluoxetine (20 mg/day orally) versus an identical-appearing placebo. For the next four weeks, patients were crossed over to the alternative arm.
The study enrolled 81 women with a history of breast cancer or a perceived increased risk of breast cancer. Sevent-two patients completed the study. Their mean age was older than 50 years.
This was a placebo-controlled, double-blind, cross-over clinical trial.
Assessments included:
At the end of the first treatment period (four weeks), hot flash scores (frequency x average severity) decreased 50% inthe fluoxetine arm versus 36% in the placebo arm. Cross-over analysis showed a significantly greater improvement in hot flash scores with fluoxetine than placebo (p = .02). More than half (54%) of the patients reported depressive symptoms of at least mild severity at baseline compared with only 30% of patients after the first treatment period and 21% after the second treatment period. After five weeks of treatment, QOL did not differ between groups. After cross-over, QOL showed a relative improvement trend for fluoxetine compared to placebo.
Age and tamoxifen use were not adjusted for as potential confounding factors.
López-Saca, J.M., & Centeno, C. (2014). Opioids prescription for symptoms relief and the impact on respiratory function: Updated evidence. Current Opinion in Supportive and Palliative Care, 8, 383–390.
STUDY PURPOSE: To review evidence regarding the use of opioids for dyspnea and associated risks of respiratory depression
TOTAL REFERENCES RETRIEVED: 47
PHASE OF CARE: End-of-life care
APPLICATIONS: Palliative care
In studies measuring dyspnea, opioids were consistently shown to significantly reduce dyspnea and respiratory effort. A few studies described minor changes in respiratory rate and PaCO2, but they were not clinically significant.
Findings support the safety and effectiveness of opioids for the management of dyspnea in patients with advanced disease.
This review provides additional support for the effectiveness of opioids to reduce dyspnea, and provides some evidence that this does not cause significant respiratory depression.
Lopez, A.P., i Figuls, M.R., Cuchi, G.U., Berenstein, E.G., Pasies, B.A., Alegre, M.B., & Herdman, M. (2004). Systematic review of megestrol acetate in the treatment of anorexia-cachexia syndrome. Journal of Pain and Symptom Management, 27, 360–369.
To assess the efficacy and safety of megestrol acetate in improving appetite, weight gain, and health-related quality of life in patients with anorexia-cachexia syndrome who had advanced cancer, AIDS, or other underlying pathologies. Other aims were to evaluate the efficacy of different doses and the safety of megestrol acetate.
The following databases were searched: Cochrane Collaboration, Cochrane Controlled Trials Register, MEDLINE, and Embase. A hand search of reference lists was completed. The keywords used were randomized controlled clinical trial, double-blind, single-blind, megestrol acetate, terminally ill, terminal care, and wasting syndrome. Variants of megestrol acetate were also keywords. There was no language restriction. Data were extracted by two reviewers who used the Jadad scale to assess quality. A third reviewer participated if needed.
Of the 296 studies identified, 26 published between 1980 and 2002 met the inclusion criteria. Of these, 19 compared megestrol acetate to a placebo, 6 compared megestrol acetate to other drugs, and 6 studied the effectiveness of different dose levels. The quality of the studies was rated on the Jadad scale: 10 were high-quality, 7 were medium-quality, and 9 were low-quality.
A meta-analysis of the studies assessing appetite had homogeneous results, showing statistically significant improvement with megestrol acetate over the placebo (RR = 2.33, 95% CI 1.52–3.59)
For weight gain, results were homogeneous and in favor of megestrol acetate, but not statistically significant (RR = 1.88, 95% CI 1.43–2.47).
For quality of life, there was significant heterogeneity because of the variety of instruments used. When the results using only the Karnofsky Performance Status Scale were analyzed, heterogeneity was not observed, and the results were positive in favor of megestrol acetate (RR = 1.64, 95% CI 1.06–2.55). Subgroup analysis in patients with cancer showed positive results in favor of megestrol acetate over placebo on appetite (RR = 2.33, 95% CI 1.52–3.59), weight gain (RR = 2.16, 95% CI 1.45–3.21), and quality of life (RR = 1.81, 95% CI 1.13–2.89).
In comparing megestrol acetate to other drugs, it showed benefit in terms of weight gain. No difference was noted between megestrol acetate and other drugs in terms of quality of life. For appetite, megestrol acetate was superior to dronabinol, but showed no advantage to other drugs studied.
In comparing the efficacy of different megestrol acetate doses, the only statistically significant result was observed in patients with cancer, for whom higher doses were associated with greater weight gain (RR = 1.65, 95% CI 1.00–2.73). There were no statistically significant differences between treatment and placebo groups in terms of adverse events, excepting edema, which was greater in the megestrol acetate group (RR = 1.67, 95% CI 1.22–2.28).
When compared with a placebo, there were significant improvements in appetite and weight gain in patients with cancer who were treated with megestrol acetate. This meta-analysis confirms the results of earlier systematic reviews that demonstrated megestrol acetate's advantages over placebo in terms of weight gain and improved appetite. This review did not define the optimal dose of megestrol acete.
Given the adverse events profile, megestrol acetate is a safe treatment option.
Loo, W. T., Jin, L. J., Chow, L. W., Cheung, M. N., & Wang, M. (2010). Rhodiola algida improves chemotherapy-induced oral mucositis in breast cancer patients. Expert Opinion on Investigational Drugs, 19 Suppl. 1, S91-100.
Investigate Rhodiola algida on healthy human lymphocytes in vitro and on the healing time of oral ulcers in breast cancer
Secondary aim: Animal study portion
In the test group, the patients consumed 200 mL boiled Rhodiola algida at a concentration of 50 mg/ml for seven consecutive days after receiving chemotherapy. Control patients were given honey bee water. All patients were given 0.2% chlorhexidine mouthwash. Rhodiola algida is a Tibetan plant used in traditional Chinese medicine, believed to affect the immune system by nourishing Chi.
The study was comprised of 130 patients, age 24-58, with a mean age of 48.5 years.
Females: 100%
Diagnosis information: Invasive ductal carcinoma
Single site: University of Hong Kong
Control trial- not clear if it was random nor blind.
Oral Mucositis Assessment Scale (OMAS) Numeric Rating Scale for pain
There were three ulcers in the treatment group and five in the control group. The diameter of ulcers in the treatment group was smaller than those in the control group. The treatment group had less pain, shorter duration of ulceration, and better body weight maintenance than the control group, all of these parameters had statistical significance (p < 0.05). Findings related to measures of immune function are provided. The WBC count in the treatment group was 5.3 (±1.02) compared to 3.2 (±0.82) in the control group. This effect may have implications for other symptoms in addition to mucositis.
Although this study showed some improvement in oral healing and pain, this group of patients does not typically experience severe mucositis.
Breast cancer only, very few episodes of mucositis to measure effectiveness; nausea and vomiting in this population may affect weight loss.
Many other potential effects of this agent. Further research with this agent would be useful.
Longo, F., Mansueto, G., Lapadula, V., DeSanctis, R., Quadrini, S., Grande, R., … DiSeri, M. (2011). Palonosetron plus 3-day aprepitant and dexamethasone to prevent nausea and vomiting in patients receiving highly emetogenic chemotherapy. Supportive Care in Cancer, 19, 1159-1164.
To evaluate the efficacy of a regimen of three-day aprepitant, a single dose of palonosetron, and three-day dexamethasone in patients receiving cisplatin-based, highly emetogenic chemotherapy (HEC)
Patients were given the following regimen. On day 1, patients were given 0.25 mg IV palonosetron, 20 mg IV dexamethasone, and 125 mg oral aprepitant before chemotherapy; on day 2, they received 80 mg oral aprepitant and 4 mg oral or intramuscular dexamethasone; and on day 3, they were given 80 mg oral aprepitant and 4 mg oral or intramuscular dexamethasone.
Rescue therapy was 10 mg metoclopramide and 4 mg dexamethasone. Patient diaries were used to record emesis, use of rescue medication, and severity of nausea for 5 days after chemotherapy.
The study was conducted in multiple outpatient settings in Italy.
All patients were in active treatment.
This was a prospective trial.
Palonosetron in combination with aprepitant and dexamethasone was found to be effective in preventing acute and delayed nausea and vomiting with HEC.
The findings confirmed the efficacy of palonosetron as part of an antiemetic drug regimen for patients receiving HEC.
Longo, F., Mansueto, G., Lapadula, V., Stumbo, L., DelBene, G., Adua, D., … Quadrini, S. (2012). Combination of aprepitant, palonosetron and dexamethasone as antiemetic prophylaxis in lung cancer patients receiving multiple cycles of cisplatin-based chemotherapy. International Journal of Clinical Practice, 66, 753-757.
To evaluate whether the antiemetic efficacy of triple combination aprepitant, palonosetron, and dexamethasone could be sustained for up to six cycles of highly emetogenic chemotherapy (HEC) (cisplatin ≥ 50 mg/m2)
To be eligible, patients had to be chemotherapy-naïve adults with lung cancer, have an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0–2, and be receiving 4–6 cycles platinum-based therapy (cisplatin ≥ 50 mg/m2).
All eligible patients received 125 mg oral aprepitant, 0.25 mg IV palonosetron, and 20 mg IV dexamethasone before chemotherapy on day 1, and 80 mg oral aprepitant and 4 mg oral or intramuscular dexamethasone on days 2 and 3. Patients recorded all vomiting episodes, any use of rescue medication, and the severity of nausea on 4-point Likert-type scale in diaries for 5 days (0–120 hours) after chemotherapy during all planned cycles.
The study was conducted at multiple outpatient sites in Italy.
All patients were in active antitumor treatment.
This was a prospective observational study.
The triple combination of aprepitant, palonosetron, and dexamethasone enhanced antiemetic protection during the first cycle and the efficacy was sustained for up to six cycles of cisplatin-based highly emeotgenic chemotherapy (HEC) in patients with lung cancer. The majority (84%) of patients were able to complete their planned number of chemotherapy treatment cycles.
Patients with advanced stage lung cancer treated with HEC who are given CINV prophylaxis according to accepted guidelines prior to each cycle maintain the benefit from the CINV prophylaxis through all cycles of treatment. Managing the distress caused by CINV may increase overall quality of life and is an important consideration when treating patients with palliative chemotherapy.
Lokkevik, E., Skovlund, E., Reitan, J.B., Hannisdal, E., & Tanum, G. (1996). Skin treatment with Bepanthen cream versus no cream during radiotherapy. Acta Oncologica, 35, 1021–1026.
To compare Bepanthen cream with no topical ointment
Patients used Bepanthen on one side of the treatment field and used no topical treatment on the other side. Patients were instructed to not inform the physician of which region or field received the application of the cream, and they randomized their own application. Bepanthen twice a day began on day 1 of radiation therapy. Skin assessments were performed weekly during treatment and two weeks following treatment.
The study used a quasi-experimental blinded trial design.
For both cancers, all skin reactions were more severe at completion of six weeks of radiation treatments, which was chosen as a reference point to standardize assessment data. No significant difference was observed in erythema, most desquamation, itch, or pain. No significant effect of any of the variables was found in regression analysis regarding erythema and desquamation.
Bepanthen did not provide any significant benefit.
Tissue toxicity is associated with 60-cobalt.