To evaluate the efficacy of a single-dose palonosetron plus dexamethasone to control emesis in patients receiving highly emetogenic chemotherapy (HEC) and to measure any reduction of calories consumption related to CINV

At baseline, nutritional evaluation subjective global assessment and assessment of appetite were done. Patients received a single bolus of 250 mcg palonosetron plus a single dose of 20 mg dexamethasone 30 minutes prior to chemotherapy. Subjects recorded emesis, nausea, use of rescue medication, and food intake in daily diaries. Amount of food intake was quantified with the aid of pictures of standard portions.

• The study consisted of 35 patients.
• Mean age was 56 years, with a range of 48–67 years.
• The majority of patients were female (82.9%).
• Diagnoses were solid tumors (soft tissue sarcoma, cervix, bladder, lung, and breast).
• Of those patients receiving HEC, 88.6% were chemotherapy naïve, 28.6% were receiving cisplatin-based regimens, and 71.4% were on ifosfamide-epirubicin regimens.
• At baseline, 82.9% of patients were evaluated as well-nourished.

The study was conducted at a single site.

All patients were in active treatment.

This was a prospective trial (noncomparative, single-arm study).

• Patient diaries were used to record the time of each emesis and each dose of rescue medication, as well as the start and stop times of nausea and food intake. 
• Subjective global assessment of complete response (CR) was no vomiting and no rescue therapy. Complete control was defined as no more than mild nausea.
• Appetite was rated on a visual analog scale (VAS).

• CR was achieved in 85.7% of patients, and CC was achieved in 82.9% of patients in the acute phase.
• During the delayed phase, 82.9% achieved CR and 77.1% achieved CC.
• Overall, 80% achieved CR and 77.1% achieved CC. Even in patients with CC, the presence of residual nausea, although it was rated as mild, significantly decreased calorie intake during the acute and delayed phases (r² = 0.77, p < 0.0001).

Palonosetron was able to prevent both acute and delayed vomiting and nausea in most patients treated with HEC. A strong, significant relationship was found between the presence of nausea and lower caloric intake.

• The sample consisted of fewer than 100 patients.
• No control group was included. This reported provided only preliminary results.
• Aprepitant was not employed as an antiemetic for HEC.
• Patient compliance with the diary was not discussed.
• Caloric intake can only be considered an estimation based on the method of measurement.

• Even mild nausea has a negative effect on caloric intake, and, for those with severe nausea, intake may be diminished drastically.
• Findings support the observation that palonosetron is useful in the prevention of CINV in patients receiving HEC.

To assess the efficacy of a single dose of palonosetron and dexamethasone to prevent chemotherapy-induced nausea and vomiting (CINV) and guarantee an adequate food intake in patients receiving several cycles of multiple-day-based chemotherapy

Patients with advanced cancer but without a compromised nutritional status (bone mass > 18.5) receiving multiple cycles of multiple days (MD-CT) were treated with 0.25 mg palonosetron over 30 seconds and 20 mg dexamethasone 30 minutes prior to chemotherapy. Patients recorded the number and intensity of emesis episodes, use of rescue medication, and the time and amount of daily food intake including pictures when available.

• The study consisted of 50 patients, none of whom were severly malnourished.
• The median age was 56.8 years.
• The sample was 18% male and 82% female.
• Cancer diagnoses were sarcoma (52%), cervix (34%), bladder (6%), breast (6%), and lung (2%).
• The majority of patients (74%) were chemotherapy naïve.
• Patients had normal renal and liver function, no uncontrolled vomiting, and no intestinal obstruction, peritonitis, serious mucositis, or infections.

This study was conducted at a single site at a hospital in Lecee, Italy.

• Patients were in active treatment.
• This study has application to elderly care.

This was a prospective, uncontrolled trial.

• Patients recorded complete response (CR), defined as no vomiting and no use of rescue medications, in diaries.
• Patients quoted their daily food intake, the time food was consumed, and the amount of each portion eaten. Amount were quantified using pictures of standard portions included in the diary.  
• Diaries had to be completed from day 1 to the end of day 7 (168 hours postchemotherapy).

• During the 6 cycles, CR ranged from 76%–88%.
• Complete Control (CC), defined as no vomiting, no rescue medication, and no more than mild nausea, ranged from 62%–88%.
• Total Control (TC), defined as no vomiting, no rescue medication, and no nausea, ranged from 54%–80%.
• The correlation between severity of nausea and the amount of food intake remained uniform during all cycles.  Patients with CR had a significant higher weekly food intake than those using rescue medication or vomiting.
• Patients who experienced CC and no nausea had a median weekly for intake ranging from 11,102–12,200 kcal compared to patients with CC, but patients with mild nausea had a lower median weekly food intake.

• A single dose of palonosetron and dexamethasone were shown to be effective in prevention of vomiting and nausea in patients receiving multiple day-based chemotherapy and the effectiveness last over six cycles.
• The use of dexamethasone was limited to day one, which may eliminate steroid side effects over multiple cycles.
• A direct correlation was found between severity of nausea and weekly caloric intake. Even mild nausea caused a decrease in kcal consumed between 2,102 to 2,957.  This was maintained across all six cycles.
   

• The sample size was small with fewer than 100 patients.
• Large and randomized studies are needed to assess the role of CINV on food intake in both multiple-day and single-day chemotherapy.  
• Why aprepitant was not used for this highly emetogenic combination of chemotherapy agents is not known as aprepitant is indicated in Oncology Nursing Society (ONS), National Comprehensive Cancer Network (NCCN) and American Society of Clinical Oncology (ASCO) guidelines in combination with a 5-HT₃ and steriod.

A direct correlation exists between mild nausea and significant decrease in food intake. Patients can easily become malnourished. Nurses need to assess closely for nausea, using a Likert-type scale and weight loss and malnutrition.

Palonosetron and dexamethasone can achieve high control of CINV during multiple days and multiple cycles of HEC. Nurses need to use instruments like the subjective global assessment (SGA) used in this study to better identify patients at risk for malnourishment rather than reyling solely on body mass index (BMI).

Patients receiving carboplatin (area under the curve [AUC] 5 mg per minute/ml) and 175 mg/m² paclitaxel were randomly assigned to receive 910 mg/m² IV amifostine 30 minutes prior to carboplatin.

• Patients were diagnosed with stage 2–4 ovarian cancer.
• The study reported on a sample of 187 patients (93 in the amifostine group and 94 in the control group).

The study was conducted between April 1999 and July 2001.

This was a phase III, multicenter, randomized trial.

• Grade 3-4 toxicity was reported.
• The National Cancer Institute (NCI) Common Terminology Criteria (CTC) was used.

A significant difference was found in grade 3-4 mucositis (4.7% in the amifostine group versus 15.4% in the control group, p < 0.0001).

• The study was not double blinded.
• The authors did not indicate clearly how mucositis was measured.
• The data in the article was not clear and specific.

To provide a definitive test of the effectiveness of calcium and magnesium in decreasing oxaliplatin-induced neurotoxicity

Patients randomly were assigned to receive intravenous calcium gluconate and magnesium sulfate at 1 g each in 100 ml of D5W over the course of 30 minutes immediately prior to and after each dose of oxaliplatin. Patients in the control group received a placebo that appeared identical to the study drug with the same administration timing. A third group was administered calcium and magnesium before chemotherapy and a placebo after infusion. Patients with adenocarcinoma of the colon scheduled to receive 12 cycles of FOLFOX chemotherapy including 85 mg/m² oxaliplatin every two weeks were considered for participation. Oxaliplatin dose modifications were not prescribed by the study, but dosage changes or delays were provided as recommendations. Study measures were obtained at each cycle of chemotherapy.

• N = 326 
• MEDIAN AGE = 56 years
• MALES: 48%, FEMALES: 52%
• KEY DISEASE CHARACTERISTICS: All participants were patients with colon cancer receiving either FOLFOX-4 or mFOLFOX-6 treatment.
• OTHER KEY SAMPLE CHARACTERISTICS: 85% Caucasian; majority were diagnosed with stage II disease

• SITE: Multi-site  
• SETTING TYPE: Multiple settings    
• LOCATION: More than 50 sites in the United States

• PHASE OF CARE: Active antitumor treatment

Three-group, double-blinded, placebo-controlled, randomized trial

• European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ) for Chemotherapy-Induced Peripheral Neuropathy (CIPN20)
• National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE)

There were no significant differences between the three study arms on the EORTC-QLQ CIPN20 sensory or motor neuropathy scales. There were no significant differences in neurotoxicity assessment using the CTCAE to determine time till grade 2 neurotoxicity or incidence of grade 2 symptoms. A subgroup analysis did not show evidence of benefit in groups according to age, sex, disease stage, or specific FOLFOX regimen. There were no differences in acute or chronic symptoms.

The findings of this study do not support the use of intravenous calcium gluconate and magnesium sulfate to prevent oxaliplatin-induced neuropathy.

This large, well designed trial showed no benefit of the use of a calcium gluconate and magnesium sulfate infusions to prevent peripheral neuropathy in patients receiving FOLFOX. The authors of this study state that as many as 50% of practitioners continue to use this intervention, and resources such as UpToDate suggest consideration of this intervention. Nurses can advocate that calcium gluconate and magnesium sulfate not be used for the prevention of peripheral neuropathy given the lack of evidence for its efficacy. This can save time and expense in treatment for patients receiving this type of chemotherapy. Additional similar research may be needed to examine this treatment's effects in patients at risk for peripheral neuropathy related to other chemotherapeutic agents.

Assess more definitively than previous studies the efficacy and toxicity of various doses of venlafaxine for treatment of hot flashes in the breast cancer survivor

Participants were assigned to placebo (n = 56), or venlafaxine 37.5 mg daily (n = 56), 75 mg daily (n = 55), or 150 mg daily (n = 54).

Patients eligible for this trial were 221 women who had a history of breast cancer or who were concerned about taking estrogen therapy for fear of developing breast cancer.

• Inclusion criteria:
  • Troublesome hot flashes, occurring at least 14 times per week; hot flashes severe enough for the patient to desire therapeutic intervention, and present for at least one month prior to study entry, older than 18 years; life expectancy at least 6 months; and ECOG performance status of 0–1.
  • Anti-estrogens and aromatase inhibitors were allowed if they had been started four weeks prior to study entry and scheduled to continue for the next five weeks.
• Exclusion criteria:
  • Concomitant therapies not allowed: antineoplastic chemotherapy, androgens, estrogens, progestins, antidepressants, clonidine, and combined ergotamine, alkaloids of belladonna, and phenobarbital.   
  • Use of venlafaxine in the past, any antidepressant treatment within the preceding two years, pregnancy, breastfeeding, use of other medications to treat hot flashes within the past two weeks, uncontrolled hypertension.

Double-blind, placebo-controlled, randomized trial

• The primary endpoint:  bivariate construct of average daily hot flash activity: the number of hot flashes and a score combining the number and severity of hot flashes
• Hot flash diaries
• Participants stratified by age (younger than 50 versus older than 50), current tamoxifen use, duration of hot flashes (less than 9 versus more than 9 months) and frequency of hot flashes/day.

It was calculated that a sample size of 50 patients per group would provide 80% power to detect differences in average hot-flash activity of standard deviation (SD) 0–6 (1–2 hot flashes per day, a score of 3 units, or a 21% fall from baseline) with a type 1 error rate of 5%.

Of the 229 patients who joined the study, 191 had data evaluable over the whole study period (50 from the placebo group, 49 from the venlafaxine 37.5 mg group, 43 from the venlafaxine 75 mg group, and 49 from the venlafaxine 150 mg group). After week 4 of treatment, median hot flash scores were reduced from baseline by 27%, 37%, 61%, and 61%, respectively, in the four groups. Frequencies of some side effects (mouth dryness, decreased appetite, nausea, and constipation) were significantly higher in the venlafaxine 75 mg and 150 mg groups than in the placebo group.

The trial suggests that venlafaxine can alleviate hot flashes and that the most appropriate dose for this indication is 75 mg.

Missing data were handled in several ways as a sensitivity analysis of the robustness of the results in relation to the missing data. Less than 10% of possible data were missing, and the results were consistent across a series of analyses by various imputation methods.

The study makes mention that venlafaxine may also be effective against hot flashes in men who have undergone androgen deprivation therapy for prostate cancer.

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.

Efficacy and side-effects of three relatively low gabapentin doses in comparison to placebo.

Randomized to:

• Placebo for 28 days, or
• Gabapentin 300 mg at bedtime for 28 days, or
• Gabapentin 300 mg at bedtime for 7 days then 300 mg twice a day for 7 days then 300 mg three times a day for 14 days

• Men undergoing androgen deprivation therapy for prostate cancer with at least 14 hot flashes per week.
• N = 223; 214 completed the study.
• Mean age: 70 years old
• Inclusion: Men with a history of prostate cancer on a program of androgen ablation hormone therapy four weeks prior study and planning continuation of therapy during study; bothersome hot flashes of at least 14 times per week with hot flashes present at least 1 month prior study entry; Antidepressant use at least one month prior study with continuation during study trial.
• Exclusion: Renal insufficiency; concurrent therapies, including antineoplastic chemotherapy, androgens, estrogens, or progestational agents; previous therapy with gabapentin

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

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

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.

• Inclusion criteria:
  • Women with a history of breast cancer or a perceived increased risk of breast cancer 
  • Patients without current evidence of malignant disease 
  • History of bothersome hot flashes (at least 14 per week) that were severe enough for patients to desire intervention; hot flashes present for at least one month
  • Concomitant therapy with tamoxifen or raloxifene was permitted if patient wason  therapy for at least one month and was planning continuation of therapy during study.
• Exclusion criteria:
  • Concomitant therapy with antineoplastic chemotherapy, androgens, estrogens, progestational drugs, or warfarin use
  • Previous use of fluoxetine antidepressant use for two years prior to study entry

This was a placebo-controlled, double-blind, cross-over clinical trial.

Assessments included:

• Daily hot flash diary for nine weeks
• Toxicity questionnaire weekly
• Beck Depression Inventory
• Uniscale global QOL instrument at study entry and study completion

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.

STUDY PURPOSE: To review evidence regarding the use of opioids for dyspnea and associated risks of respiratory depression

• DATABASES USED: MEDLINE, TRIP database, Cochrane Collaboration 
• KEYWORDS: MESH terms for morphine; respiratory insufficiency or respiratory function; and opioid. Search terms provided in the article
• EXCLUSION CRITERIA: Studies in pediatric patients

TOTAL REFERENCES RETRIEVED: 47

• FINAL NUMBER STUDIES INCLUDED = 8 
• TOTAL PATIENTS INCLUDED IN REVIEW = 118
• SAMPLE RANGE ACROSS STUDIES: 9–31 patients
• KEY SAMPLE CHARACTERISTICS: Various disease types, including cancer

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.

• Limited number of studies
• Small samples

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.