To compare effects of compression garment versus compression bandaging in women receiving complete decongestive therapy for arm lymphedema

Therapy for all patients included manual lymphatic drainage five days per week over a two-week period. During initial treatment, patients were randomly assigned to wear a compression glove and sleeve or compression bandages day and night as tolerated. At the end of two weeks, all were provided with a new sleeve and glove, which was worn only during the day. They were instructed in skin care. Participants completed study measurement of lymphedema at baseline and on days 5 and 10 and then at 3 months.

• N  23       
• MEAN AGE = 60.5 (range = 44–76)
• FEMALES: 100%

• Randomized, controlled trial

• Arm circumference measurement
• Water displacement for arm volume
• Visual analogue scales (VAS) scaes for pain, heaviness, and tension of the arm
• Disabilities of Arm Shoulder and Hand (DASH) questionnaire

There were no difference between groups in arm volume or DASH scores at 10 week or 3 months. There were no differences between groups in VAS symptom scores. There was a trend toward lower arm volumes but higher DASH scores with compression bandaging.

Findings showed no significant differences in effect of compression bandaging versus use of compression garments during the first two weeks of therapy for arm lymphedema.

• Key sample group differences that could influence results

Findings suggest that compression garment and compression bandaging use during initial phase of CDT for arm lymphedema yielded similar results. There was a trend suggesting lower arm volume, but higher disability scores with bandaging; however, no firm conclusions can be drawn due to lack of statistical significance and the small sample size. Ongoing work is important to determine which treatment approaches are better tolerated by patients and degree of comparative effectiveness combined with tolerance.

To investigate the safety and effectiveness of pregabalin for reducing postoperative pain in patients who have undergone mastectomy

Patients were randomly assigned to receive either pregabalin or placebo at 1 hour before surgery and at 12 hours after the initial dose. All patients received the same anesthesia and all received 100 mg aceclofenac twice a day the day after surgery. Assessment of pain and for adverse effects was done at 1, 6, 24, and 48 hours postoperatively. If a patient’s pain intensity was 5 or greater or if the patient requested analgesia, additional pain medication was provided. After discharge from the hospital, at one week and one month postoperatively, patients were contacted by phone for pain scoring.

• The sample was composed of 84 patients.
• Mean patient age was 50 years (SD = 8 years).
• All patients were female.
• All patients had breast cancer and underwent mastectomy during the study.

• Single site
• Inpatient
• South Korea

Double-blind placebo-controlled randomized study

• 11-point verbal rating scale, to rate pain
• 4-point scale, to rate severity of side effects

• At 1, 24, and 48 hours postoperatively, scores for pain at rest were lower in the pregabalin group than in the placebo group (P < 0.05). At the same general time periods, pain with movement was lower in the pregabalin group than in the placebo group.
• Average differences in pain scores between groups were 1 point at most measurement periods. In the pregabalin group, pain intensity at one week postoperatively was 2 points lower on average than that in the placebo group.
• Compared to patients in the placebo group, fewer patients in the pregabalin group required rescue analgesics during the first 48 hours after surgery, but this difference was not significant.
• There were no differences in pain scores at six hours postoperatively, a fact that may have been due to the timing of premedication and the half-life of pregabalin.
• There were no differences between groups in sedation scores or other side effects.

Perioperative pregabalin may improve postoperative pain control in patients who have undergone mastectomy.

• The study had a small sample size, with fewer than 100 patients.
• Authors did not analyze total use of rescue analgesics, so actual differences between groups, in regard to total analgesic needs, is undetermined.
• The study included no subgroup analysis of patients who had partial versus total mastectomy or axillary lymph node dissection or not. Patients who had more extensive surgery would probably have more pain. Each group contained similar numbers of patients who had undergone surgery of the same extent.

Perioperative administration of pregabalin may be helpful in the management of postoperative pain. This study does not establish the most effective timing of administration. Nurses should be aware of the common side effects of pregabalin (dizziness and sedation), which other studies have established. These side effects may complicate postanesthesia assessment.

To study the effectiveness of mirtazapine on various cancer-related symptoms, such as nausea, sleep disturbance, pain, and depression.

Patients were treated at a starting dosage of 15 mg of mirtazapine in orally disintegrating tablets a day. The dosage was titrated between 15 and 45 mg per day based on clinical judgment. Mean treatment dosage was 19.6 mg per day in the total population and 22.9 mg in those who completed the study. Patients were administered serial assessments at baseline and on days 1, 3, 5, 7, 14, and 28.

• The sample was comprised of 42 patients (55% males, 45% females).
• Mean age was 57.5 years (standard deviation = 12 years; range 22–79 years).
• Patients had mixed cancers, 59% of which were lung, breast, gastrointestinal, hepatobiliary tract, or other. Of the patients, 61% had stage IV cancer.
• Patients had malignant cancer AND nausea or insomnia.

• Single site
• Inpatient (88%)
• Korea

The study used a prospective, open-label, repeated measure design.

• Clinical Global Impression (CGI) scale for nausea/vomiting 
• Chonnam National University Hospital–Leeds Sleep Evaluation Questionnaire (C-LSEQ)
• Montgomery–Åsberg Depression Rating Scale (MADRS) (two items):  reduced sleep and reduced appetite 
• MÅDRS total score:  10-item objective rating scale to assess depression
• Short Form Health Survey 36 (SF-36) (two bodily pain items)
• EuroQOL (EQ)-5D
• Udvalg for KliniskeUndersogelser (UKU) scale for sleepiness/sedation and dizziness

Nausea improved significantly from day 1 after administration of mirtazapine (p < 0.001). Improvement was sustained throughout the treatment and seemed to work best for patients actively receiving chemotherapy. In addition, anorexia improved. All sleep measures improved, many as early as day 1, but at least one measure (ease of wakening) did not improve until day 5 (p < 0.001). Mirtazapine increased sleepiness in one of three patients, but this resolved after several days on therapy. Reduction in pain scores (p < 0.5), improvement in depression score (p < 0.01), and overall quality of life (QOL) (p < 0.01) were noted as well.

Mirtazapine may be helpful in treating the cancer-related symptoms of nausea, sleep disturbance, anorexia, pain, and depression, as well as improving QOL.

• The study had a small sample size, with less than 100 patients.
• The mirtazapine dosage varied.
• The study had a high drop-out rate.
• The patients were a heterogeneous group as far as concomitant medications were concerned. These were not controlled for, and patients were allowed to continue preexisting medications for nausea, hypnotics, and analgesics.
• The percentage of inpatients was high.

Mirtazapine may be useful in treating chemotherapy-related symptoms, especially sleep disturbance and nausea, in patients with malignant cancers.

To compare the efficacy and safety of the combination of ramosetron, aprepitant, and dexamethasone (RAD) with the efficacy and safety of the combination of ondansetron, aprepitant, and dexamethasone (OAD) in treating highly emetogenic chemotherapy (HEC)-induced nausea and vomiting

Patients were assigned to either the RAD or OAD groups (1:1 ratio) according to a stratified block randomization table. Aprepitant (125 mg one hour prior to chemotherapy on day 1 and 80 mg on days 2–3) and dexamethasone (12 mg 30 minutes prior to chemotherapy on day 1 and 8 mg on days 2–4) were administered orally. Ramosetron (0.3 mg on day 1) and ondansetron (16 mg on day 1) were administered IV to the RAD group and OAD group, respectively, 30 minutes before chemotherapy. Rescue antiemetics were used per the attending physician’s discretion. Patients were then asked to keep a record of vomiting or retching episodes in a diary and Rhodes Index of Nausea and Vomiting scores for five days.

• N = 338   
• AGE = 197 were older than 65 years 
• MALES: 79.2% (RAD), 58.1% (OAD); FEMALES: 20.8% (RAD), 41.9% (OAD) 
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Patients with a pathologically confirmed malignant disease who were scheduled to receive HEC on their first day of treatment. Most patients had lung cancer.
• OTHER KEY SAMPLE CHARACTERISTICS: Mostly patients with lung cancer, chemotherapy naïve patients, patients on cisplatin-containing regimens, and patients who were on a single-day regimen

• SITE: Multi-site   
• SETTING TYPE: Multiple settings    
• LOCATION: Seventeen institutions of the Korean Cancer Study Group

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Elder care 

• Prospective, single-blind, randomized

• Rhodes Index of Nausea and Vomiting-Form 2
• Common Toxicity Criteria for Adverse Events (CTCAE)
• Chi-square test
• Fisher exact test
• Wilcoxon rank-sum test
• Visual analog scale (VAS)
• Generalized estimating equations (GEE)

Complete response (CR) rates for the acute, delayed, and overall phases were similar for both the ramosetron- and ondansetron-based regimens. No differences existed between groups in the use of rescue medication.

RAD was noninferior to OAD in the prevention of HEC-induced nausea and vomiting irrespective of patient age, type of cancer, or chemotherapeutic regimen. RAD demonstrated efficacy in the acute, delayed, and overall phases. RAD was more effective than OAD in men.

• Risk of bias (no blinding)
• Risk of bias (sample characteristics)
• Patients with various diseases and chemotherapeutic regimens

RAD can be considered a standard regimen for HEC-induced nausea and vomiting. The adverse event rate is similar to ondansetron.

To evaluate the efficacy of combination antiemetic therapy including 5HT3 receptor antagonists, neurokinin-1 (NK1) receptor antagonists, and dexamethasone for multiple highly emetogenic anticancer agents in patients with bone and soft tissue sarcoma; to compare the effectiveness of single-shot palonosetron and consecutive-day granisetron

A single randomization method was used to assign eligible patients to the palonosetron or granisetron arm. Patients in the palonosetron arm received a palonosetron regimen during the first and third chemotherapy courses and a granisetron regimen the second and fourth courses. Patients in the granisetron arm received granisetron during the first and third courses and palonosetron the second and fourth. All patients received an NK1 receptor antagonist and dexamethasone. Patients receiving the palonosetron regimen were administered 0.75 mg of palonosetron on day 1, and patients receiving the granisetron regimen received 3 mg of granisetron twice daily on days 1–4 and once on day 5. Patients were followed for 10 days during each course for efficacy and safety endpoints. On days 4 and 10, patients responded to a questionnaire about emetic experiences and rescue medication use. Nausea severity was rated from 0–10 according to subjective assessments during the acute and delayed phases.

• N = 24
• MEAN AGE = 43.4 eyars (range = 15–70 years)
• MALES: 50%, FEMALES: 50%
• KEY DISEASE CHARACTERISTICS: Nine patients with osteosarcoma; eight with malignant fibrous histiocytoma; two with leiomyosarcoma; five with other bone or soft tissue sarcomas; receiving highly emetogenic chemotherapy

• SITE: Single site    
• SETTING TYPE: Not specified  
• LOCATION: Japan

• PHASE OF CARE: Active antitumor treatment

Randomized, single-blinded crossover study

• No specific instruments were listed for the questionnaire (which included number of emetic episodes, use of rescue therapy, nausea severity rated on scale of 0–10, and patient’s preferred regimen).
• Toxicity data were graded according to Common Terminology Criteria for Adverse Events (CTCAE)-adapted toxicity grades.

The overall complete response rate was 66 out of 96 courses (69%) for the acute phase, 38 out of 96 (40%) for the delayed phase, and 33 out of 96 (34%) overall. In the acute phase, complete responses were achieved in 34 out of 48 courses (71%) of the palonosetron regimen and 33 out of 48 courses (69%) of the granisetron regimen. In the delayed phase, complete responses were achieved in 18 courses (38%) of the palonosetron regimen and 20 courses (42%) of the granisetron regimen. There were no statistically significant differences in complete responses for either regimen. Patient preference was recorded for 15 patients. Two patients (13%) preferred palonosetron, three patients (20%) preferred granisetron, and 10 patients (67%) reported that both antiemetic regimens had similar efficacies. The amount of time till the first administration of rescue therapy tended to be longer in the granisetron regimen (5.65 days) compared to palonosetron (5.12 days), but this was not statistically significant (p = 0.115). For palonosetron, regimen rescue therapy was administered in 24 out of 48 courses compared to 17 out of 48 courses for the granisetron regimen. Nausea severity was slightly greater with granisetron (3.58 acute phase, 4.04 delayed) than palonosetron (3.40 acute phase, 3.92 delayed), but this was not statistically significant.

Antiemetic therapy with a three-drug combination was not sufficient to control chemotherapy-induced nausea and vomiting during chemotherapy with multiple highly emetogenic chemotherapy agents for bone and soft tissue sarcoma. However, consecutive-day granisetron was not inferior to single-shot palonosetron for treating chemotherpy-induced nausea and vomiting.

• Small sample (< 30)
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Other limitations/explanation: Did not use National Comprehensive Cancer Network-recommended dosage of dexamethasone for highly emetogenic chemotherapy (12 mg on day 1 and 8 mg daily on subsequent days [study used 6.6 mg daily])

This study demonstrated that granisetron given in consecutive-day dosing was not inferior to single-dose palonosetron in triplet therapy for highly emetogenic chemotherapy in patients with bone or soft tissue sarcoma. However, neither combination therapy was adequate to control chemotherapy-induced nausea and vomiting in this population. The development of novel antiemetic agents, or new combination therapies with existing agents such as olanzapine, was recommended. The appropriate dosing of all agents in combination therapy is an important consideration.

This study assessed the effect of sertraline on the frequency and severity of hot flashes, mood status, and health-related QOL in women with breast cancer.

Patients were randomized to receive 50 mg sertraline each morning for six weeks, followed by six weeks of a placebo tablet each morning, or to six weeks of a placebo followed by six weeks of sertraline. Before starting the medication, a one-week pretreatment period was included during which patients recorded baseline measurements of hot flashes in a daily diary.

The study enrolled adult women with localized breast cancer (stages 0–IIIB) who were receiving adjuvant tamoxifen therapy and had at least one hot flash per day.

• Inclusion criteria: Normal hepatic function with total bilirubin of less than 2 mg/dl and aspartate aminotransferase (AST) greater than or equal to two times normal within six months of study entry.
• Exclusion criteria:
  • Women who were pregnant or breastfeeding; had a history of seizure disorder; hepatic or renal insufficiency.
  • Concurrent or planned therapy with estrogen, progestational agents, corticosteroids, androgens, or other antidepressant therapy.
  • Monoamine oxidase inhibitors or other SSRI use had to have been discontinued at least 14 days before entering the study.

The study was conducted in an oncology clinic in a tertiary care center.

This was a randomized, double-blind, placebo-controlled, crossover study.

Participants maintained a daily hot flash diary to record hot flash frequency and severity. Other instruments included:

• The Center for Epidemiologic Studies depression scale
• Functional Assessment of Cancer Therapy-Breast (FACT-B) 

Measurements were assessed at baseline, 6 weeks, and 12 weeks.

The baseline daily hot flash frequency and score were 5.8 and 11.5. At the end of six weeks, frequency of hot flashes decreased by 50% in a greater proportion of those taking sertraline than those in the control group. In crossover analysis, sertraline was significantly more effective that placebo: (p= 0.03 ). Forty-eight percent preferred the sertraline period, 11% preferred the placebo period, and 41% had no preference (p = 0.006). Measures of depression and QOL were unchaged within treatment groups.

Limitations included:

• Small sample size less than 100
• Unable to detect statistically significant difference in the effect of sertraline versus placebo on hot flashes at six weeks

This was an educational intervention on the side effects of radiation therapy (RT) for prostate cancer; a four-minute followed by an eight-minute tape-recorded message (informational intervention versus standard of care information) was used at treatment 1, and a different message was used at treatment 5. The outcome was the severity of the side effects from RT.

• The sample was comprised of 152 patients receiving RT for curative, localized, prostate cancer.
• Mean age was 70.8 years.
• Of the patients, 96% were Caucasian.
• Of the patients, 13% were in stage A, 66% were in stage B, and 21% were in stage C.

• Eight cancer centers
• Eastern United States

Patients were undergoing the active treatment phase of care.

The study was a randomized, controlled trial.

A single-item measure of sleep was obtained at week 2 and the end of treatment.

A brief educational intervention is helpful in reducing sleep problems resulting from RT and cancer.

• Baseline symptom severity was not measured.
• Cost is incurred when developing the tape-recorded messages.

No training is required.

To evaluate the efficacy and safety of recombinant human epidermal growth factor (rhEGF) oral spray for the prevention of oral mucositis

Patients were randomly assigned to rhEGF or placebo oral spray. The spray was applied to the entire oral mucosa twice daily from the first day of conditioning chemotherapy until neutrophil recovery. The spray was used six times for each application. Patients were not to eat or drink for 30 minutes after application. The severity of oral mucositis was recorded daily.

• N = 136   
• MEAN AGE = 52 years
• AGE RANGE = 18–65 years
• MALES: 51.5%, FEMALES: 48.5%
• CURRENT TREATMENT: Combination radiation and chemotherapy
• KEY DISEASE CHARACTERISTICS: Patients undergoing hematopoietic cell transplantation (HCT). Most had lymphoma or multiple myeloma. Ninety-six percent had autologous HCT.

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: Republic of Korea

PHASE OF CARE: Active antitumor treatment

Double-blind, placebo-controlled, randomized, controlled trial

• Common Terminology Criteria for Adverse Events (CTCAE), version 3.0
• Oral Mucositis Daily Questionnaire

No significant difference existed between groups in the incidence of mucositis grade 2 or higher. Subgroup analysis by specific chemotherapy used also did not show any difference. Patients in the study group received less cumulative dose of opioids (p = 0.046) and for a shorter duration (p = 0.036) than those in the control group. No differences between groups in adverse events were reported.

rhEGF oral spray did not reduce the incidence of grade 2 or higher mucositis. This might have a beneficial effect in terms of the reduction of pain associated with oral mucositis.

rhEGF was not shown to have a preventive effect for oral mucositis among patients receiving high-dose chemotherapy prior to HCT. The oral spray examined here may have some positive effect for pain reduction. Additional research is needed to evaluate this potential use.

Evaluate the effect of topical rhEGF spray for the prevention and treatment of OM in patients receiving intensive chemotherapy followed by HSCT for hematoplogic malignancies.

Patients were randomly assigned to spray either 50 µg/ml rhEGF or placebo over entire oral mucosa twice daily. Investigators evaluated adherence by examining residual volume of the spray on a daily basis.

The study was comprised of 58 patients, with a median age of 56.5 years and a range of 18-63.
MALES 53.6%, FEMALES 46.4%
KEY DISEASE CHARACTERISTICS: multiple myeloma, non-Hodgkin lymphoma, ALL, MDS
OTHER KEY SAMPLE CHARACTERISTICS: intensive chemotherapy followed by autologous or allogeneic HSCT

SITE: Single site

SETTING TYPE: Inpatient

LOCATION: South Korea

PHASE OF CARE: Active antitumor treatment

Phase II randomized, double-blind placebo-controlled

NCI Common terminology Criteria for Adverse Events (CTCAE), WHO scale, ECOG, modified Oral Mucositis Daily Questionaire  (OMDQ)

Incidence of NCI grade ≥2 OM 78.6% rhEGF group, 50% in placebo group (p = 0.0496); time to NCI grade 2, 11 days rhEGF; day 10 placebo (p = 0.843), median duration NCI grade ≥2 8.5 days rhEGF and 14.5 days placebo (p = 0.262).

NCI grade ≥3 OM 39.3% in rhEFG group, 32.1% in placebo group (p = 0.577) with median duration eight days rhEGF  versus 16 days placebo group (p = 0.381; QMDQ questionnaire showed reduced limitations in swallowing and drinking in rhEGF group.

rhEGF did not reduce incidence of NCI grade ≥2 OM. Severe OM with WHO grade ≥3 in rhEGF group had shorter duration of TPN use and opioid analgesic use.

Small sample (<100)

OM is debilitating for patients receiving intensive chemotherapy for hematologic malignancies and can lead to resource intensive episodes. To date, IV palifermin is the only available treatment modality for prevention or treatment of OM. Further research is needed to identify other modalities and to continue to explore the effects of rhEGF on prevention and treatment of chemotherapy-induced OM.

To compare the effectiveness of a stellate ganglion block (SGB) versus complete decongestive therapy (CDT) for the treatment of lymphedema in patients with breast cancer

Medical records were used to collect data from patients with secondary lymphedema after treatment for breast cancer. Patients who received an SGB were selected, and a cohort of patients who received CDT matched by age, lymphedema duration, type of surgery, and history of lymph node dissection, which were obtained for comparison. SGBs were done three times, once every two weeks, via an injection of a lidocaine and triamcinolone mixture. Patients in the SGB group also did self-massage. In the CDT group, lymphedema measurements were taken after two weeks. In the SGB group, measurements were taken two weeks after each block was performed.

• N = 60  
• MEAN AGE = 58.2 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Only unlilateral arm lymphedema cases were included. The average duration of lymphedema was 17.5 months, and the time range since mastectomy was 30–35 months. 
• OTHER KEY SAMPLE CHARACTERISTICS: All patients had chemotherapy, and most also had radiotherapy.

• SITE: Single site  
• SETTING TYPE: Outpatient    
• LOCATION: South Korea

• PHASE OF CARE: Active antitumor treatment

Retrospective cohort comparison

• Arm circumference measurements

The effects of treatments on forearm measurement were 1.03 cm and 1.26 cm for CDT and SGB, respectively. This difference was not significant. Upper arm measurements were 0.94 cm after CDT and 1.81 cm after SGB (p < 0.01). SGB-related changes were only seen after the third block. In both groups, there was a significant reduction in arm circumference after the intervention (p < 0.001).

Both CDT and serial SGBs were associated with reductions in arm lymphedema. The findings of this study showed greater reductions on average with SGBs.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)

This study suggests that SGBs may be an effective alternative treatment for arm lymphedema after surgery for breast cancer. Additional research in this area is needed.