To determine whether naproxen could prevent or decrease the incidence and/or severity of pegfilgrastim-induced bone pain

A baseline assessment questionnaire was administered prior to treatment asking the presence, location, and duration of bone or joint pain, as well as how the pain was treated. A second set of questions asking whether there was development of new bone or joint pain, location, onset, duration, and severity of the effect of the assigned medication was given to patients at the time of pegfilgrastim administration. Any additional analgesia taken by the patient was also recorded. Questionnaires were completed at home and mailed. Patients were telephoned at home as a reminder to mail in their questionnaires. Enrolled patients received 500 mg of naproxen PO or placebo instructed to take prior to pegfilgrastim and continue BID. Patients were then asked to record pain severity on a 0–10 scale and duration in a daily diary. Serious adverse events (SAEs) were reported to local investigators at the University of Rochester Cancer Center Community Clinical Oncology Program research base. Other symptoms were recorded but not reportable (e.g., sleep disturbance, pain other than bone pain, fatigue).

• The study reported on 510 patients.
• The sample was 86% female and 14% male.
• Patients had a diagnosis of nonmyeloid cancer, including breast (67%), lung (10%), gynecologic (6%), hematologic (7%), and other cancers (7%).
• Patients were 18 years of age or older and were able to understand English. 
• Patients were excluded from the study if they were pregnant or nursing or had active gastrointestinal (GI) bleeding, history of GI bleeding, history of gastric or duodenal ulcers, heart surgery in the past six months, allergy to nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin, and a creatinine level more than 1.5 times the upper limit of normal. They could not be taking NSAIDs or therapeutic dose of aspirin or warfarin.

• Mutlisite (multicenter trial)
• Setting not specified

• Patients were undergoing active treatment.
• The study has clinical applicability for elderly care; late effects and survivorship; and end-of-life and palliative care.

The study was a phase III, double-blind, placebo-controlled, randomized trial.

• Pain questionnaire
• Standard symptom inventory
• National Cancer Institute’s Common Terminology Criteria for Adverse Events
• Daily diary rating pain (0–10 scale), severity, and duration

African Americans experienced more bone pain than white patients. The naproxen group showed improvement in pain reduction versus placebo. Area under the curve for pain was 7.71 for the placebo group and 6.04 for the naproxen group (p = 0.037). Naproxen decreased maximum pain from 3.40 to 2.50 (p = 0.005), incidence from 71.3% to 61.1% (p = 0.020), duration from 2.40 to 1.92 (p = 0.009), and severe pain from 27% to 19.2% (p = 0.048). Bone pain reached maximum at day 3, where naproxen patients experienced the most benefit. Patients receiving naproxen took less prescription and nonprescription pain medication. Six SAEs occurred in the naproxen group, and six SEAs occurred in the placebo group, with all SAEs unlikely or determined to be unrelated to the intervention.

There is a high incidence of pain in patients receiving pegfilgrastim. Naproxen seems to decrease incidence, duration, and severity.

The pain questionnaire was not presented in the article, and further studies may not reproduce similar results. Patients were called at home to complete the survey; prescription and nonprescription medications that were taken in addition to the naproxen and timing of the survey may have impacted results. It is also possible that the individual responding to the call may not have been the study participant. The study does not address whether individuals with other existing pain conditions were in the study or excluded or whether there were other pain conditions present at the start of the study that may have impacted results.

This study indicates there a is a difference in pain experience with different races, which may impact practice in terms of treating pain and the patient population being treated. Additional research and education are needed to investigate this difference. These results may be helpful in treating some patients’ pain; however, more work is needed to find treatments for those who cannot seek this treatment or who derive limited or no benefit from it. More than 60% of patients in this study still experienced pain, with approximately 20% experiencing severe pain. It seems this study has a good start to recognizing the existence of pegfilgrastim-induced pain and has tested a somewhat helpful intervention. However, there is still a need for more studies with different approaches to pain control and factors to predict incidence, severity, and ability to prevent pegfilgrastim-induced bone pain. The benefit of using naproxen is that it is low cost and has very few SAEs, which will need to be considered in future studies.

To evaluate the benefit of hyaluronic acid in management of radiodermatitis

Women who developed a grade 1 dermatitis with radiotherapy were randomized to use either hyaluronic acid cream or a simple urea-based emollient once daily. Patients were advised to shower one-to-two times daily. Clinical evaluation of the skin was done weekly by the radiation oncologist. Pain and quality of life were assessed at the end of treatment on day 30. The study endpoint was a success as defined by disappearance of erythema 30 days after its occurrence.

• The study sample (N = 200) was comprised of female patients with breast cancer.
• Median age was 53 years, with a range of 27–83 years.
• Median Gy was 28, with a range of 10–52 Gy.

The study used a randomised open-label phase III design.

• The Radiation Therapy Oncology Group and European Organisation for Research and Treatment of Cancer radiation toxicity scale was used.
• Erythema was measured using calorimetry.

Overall, 36.5% of participants withdrew prematurely because of worsening of eipthelitis, patient refusal, change in treatment, or use of another product. In the intent to treat population (all registered), there was a 27.3% treatment failure with hyaluronate and a 38.8% treatment failure with emollient. Power analysis showed that 100 per study group were needed. With drop outs, this study was underpowered.

 The study did not demonstrate any significant differences in epithelitis between those using hyaluronic acid or emollient topically. The study was insufficiently powered to provide any firm conclusions.

• The baseline sample differences were of import.
• The study had a risk of bias due to no blinding and sample characteristics.
• The hyaluronic acid group had a higher skin temperature at erythema area baseline. 
• Patient compliance with protocol use is not discussed, so it is not clear if use was consistent. 
• No subgroup analysis was done based on radiation therapy dosage or combined chemotherapy and radiation therapy.

Study findings are inconclusive because of the study limitations. Findings suggest that hyaluronic acid and urea-based emollients topically may provide similar results for prevention of low-grade radiodermatitis.  These findings should be viewed with caution because of the study design limitations and lack of sufficient sample size to meet power requirements.

To review the effects of guided imagery on patients with cancer experiencing pain

The type of report was systematic review.

Databases searched were PubMed, CINAHL, PsycINFO, and Cochrane Library.

Search keywords were guided imagery, cancer pain, and systematic review.

Studies were included if they were review articles published in English since 1985; the search was not limited to randomized controlled trials (RCTs).

Studies were excluded if they were clinical trials or systematic reviews that did not utilize guided imagery as an intervention, did not specifically investigate cancer pain, were not a clinical study but rather a summary of guided imagery, had a qualitative design, and were not conducted within the study time frame.

In order to focus on the most current research, this review targeted articles published during 2001–2008.

• A final number of five clinical trials were identified that included pain as either a primary or secondary outcome measure.
• Sample range across studies was 40–66 patients.
• The sample included three RCTs, one group pre/post-test design, and one RCT crossover design.

Five studies included pain as either a primary or secondary outcome measure. In three of those, pain intensity and pain-related distress decreased in the guided imagery intervention versus control for pain intensity and pain-related distress, average pain score decreased, and there was a decrease in body discomfort.

It is difficult to give concrete recommendations that guided imagery will work for all patients who suffer from cancer pain. However, based on the information from these reviews, guided imagery can be recommended as a potential aid in the relief of pain associated with cancer.

Inconsistencies and limitations included the small sample size, different patient populations, different scripts, and frequency of medication administration.

There is inconsistency in the methodological qualities of these trials. Further research is necessary to provide better evidence for the use of guided imagery in cancer pain.

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