• N = 1,014 (HEC), 848 (MEC)
• MEAN AGE = 58–59 years (Study 1 HEC, SD = 12 years), 53–54 years (Study 2 HEC, SD = 13–14 years). Demographic results of the HEC studies were reported. Data only about females participants were reported.  
• MALES: Study I = 62%, Study II = 61% (both for HEC studies), FEMALES: Study 1 = 38%, Study 2 = 39%. All results are related to the HEC studies.
• KEY DISEASE CHARACTERISTICS: Respiratory, urogenital, and others (not specified)

• SITE: Multi-site  
• SETTING TYPE: Not specified  
• LOCATION: Not specified

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

Phase III clinical trial program; included data from two HEC trials and one MEC trial

• Modified version of the Functional Living Index–Emesis (FLIE)

More patients who received the aprepitant regimen in the HEC trials achieved overall complete response compared with those on standard antiemetic therapy in cycle one adjusted for gender, region, and use of concomitant chemotherapy (67.7% versus 47.8%, p < 0.01). A significantly higher number of patients who received aprepitant reported NIDL (74.4%) as compared with those on the standard antiemetic regimen (63.9%, p < 0.01). In the HEC group, when compared to standard therapy, patients who received aprepitant reported significantly lower nausea (70.2% versus 60.9%) and vomiting (84.6% versus 68.7%, p < 0.01). In the MEC trial, reports of no emesis were significantly lower in the aprepitant group (76.2%) than in the standard regimen (61.1%, p < 0.001) after the first cycle of chemotherapy. Patients receiving aprepitant in the MEC trial had a significantly higher percentage of complete response (68.7%) than the patients in the standard regimen (56.3%, p < 0.001). Aprepitant also had a significant impact on patient report of NIDL with 73.4% reporting no impact compared to 66.3% in the standard regimen group (p < 0.05).

Aprepitant, when given with HEC, led to higher overall complete response rates than the standard regimen. Patients who received aprepitant and MEC also reported lower levels of nausea and vomiting. For patients receiving both HEC and MEC, aprepitant improved outcomes on activities of daily living (ADL).

• Patients may not be able to detect the effect of chemotherapy on their daily function.
• Recall bias could be considered as a limitation.

Aprepitant, in addition to standard CINV prophylactic medications, reduces nausea and vomiting associated with chemotherapy and decreases the impact of CINV on ADLs. This is true for patients receiving HEC and MEC. Nurses should spend time educating patients on how CINV can impact ADLs and work with patients to create patient-centered, nurse-led interventions to ease the influence of CINV on patient quality of life.

To assess the effectiveness of progressive muscle relaxation (PMR) and guided imagery training as an adjuvant intervention and accompanying antiemetics (metoclopramide, dexamethasone) in managing acute and delayed nausea and vomiting, anxiety, and depression

In the experimental group, PMR was initiated for 25 minutes and guided imagery for 5 minutes, each one hour before chemotherapy was administered.

The study reported on 71 Chinese chemotherapy-naive women with breast cancer who were older than 30 years and were receiving doxorubicin and cyclophosphamide.

The study was conducted at a university hospital outpatient treatment center in Hong Kong.

This was a randomized, controlled clinical trial.

The Profile of Mood States, State-Trait Anxiety Index, and Morrow Assessment of Nausea and Vomiting were translated into Chinese and back-translated. Measures were piloted on 25 patients prior to use in the study. Demographic data and vital signs measures were used.

The effects of PMR therapy and guided imagery were more pronounced at the initial stage of treatment when patients did not know what to expect. The effects were reduced on the fourth day and beyond. The study did not show a significant reduction in the intensity of nausea and vomiting after chemotherapy; the baseline nausea and vomiting values showed that the patients in this study began with considerably lower levels of nausea and vomiting than in previous studies. The combination of PMR and guided imagery was beneficial for cognitive distraction and relaxation, components that reduce stress and anxiety. The physiologic benefit to these techniques was discussed. Differences in Chinese and Western cultures related to expression of emotions was noted.

PMR therapy with guided imagery was found to be superior to standard antiemetic treatment alone in managing acute and delayed chemotherapy-induced nausea and vomiting.

• Pharmacologic agents prescribed were metoclopramide and dexamethasone for doxorubicin and cyclophosphamide treatment; 5-HT₃ was not given despite publication in 2002.
• Only one population (Chinese) was included.

To study the effects of P6 acupressure in the prophylaxis of chemotherapy-induced nausea and vomiting (CINV) in patients with breast cancer.

Participants were randomized to the control or experimental arm and received standard antiemetics before chemotherapy with prescriptions for antiemetics for delayed CINV that were variable.

For the experimental group, acupressure was applied using a Sea-Band® (Sea-Band Ltd.) for five days after chemotherapy administration. Researchers taught patients how to wear the bands bilaterally with the stud pressing the P6 acupoint in brief education sessions. Patients were given daily logs with the hours of the day and asked to put a mark at the hour each time that they pressed the wristband’s stud. Patients were instructed to press the stud for two to three minutes every two hours throughout the day, marking it in their log.

The control group was given antiemetics and told that they would receive acupressure instructions and wristbands with their next cycle of chemotherapy.

All participants completed questionnaires every evening after chemotherapy for five evenings. Completed questionnaires were returned directly to researchers or via pre-paid envelopes.

• The study consisted of 36 participants.
• All patients were newly diagnosed and chemotherapy naïve, starting their first cycle of chemotherapy for breast cancer, stages I-III, receiving doxorubicin or epirubicin and cyclophosphamide.
• Patients were excluded if they had received palliative chemotherapy, had a life expectancy of less than three months, had bowel obstruction, were receiving radiation therapy, or had lymphedema.

This study was conducted at a general hospital and a cancer hospital in the United Kingdom.

This was a randomized, controlled trial.

The Rhodes Index of Nausea and Vomiting was used.

Nausea and retching experience and nausea, vomiting, and retching occurrence and distress were significantly lower in the acupressure group than the control group.

At day 3, the acupressure group had a high level of nausea, vomiting, and retching, which was equal to the control group.

Acupressure at P6 is an effective intervention for managing CINV in patients with breast cancer.

• The sample size was small.
• Antiemetics for days 2-5 were not controlled.
• The study relied on patients completing daily questionnaires and returning them.

Use of the acupressure bands is easy to teach, and the bands are low in cost.

To determine the effectiveness of self-acupressure using wrist bands in the management of acute and delayed chemotherapy-induced nausea and vomiting (CINV) and to assess if the wrist bands are more effective in high, moderate, or low emetogenic chemotherapies

Patients were randomized using a method of minimization with a random element. Randomization was balanced for gender, age, and levels of emetogenic chemotherapy. Both patients and treating physicians were blinded to group. Patients received an acupressure wrist band, a sham acupressure wrist band, or no wrist band. All patients received the standard antiemetic regimen based on American Society of Clinical Oncology (ASCO) and Multinational Association of Supportive Care in Cancer (MASCC) guidelines with the exception of NK1-receptor antagonists, which were not available. The acupressure wrist bands are elastic with a 1 cm round plastic button. The button was worn at the P6 acupoint after patients were trained on the appropriate location to wear the button. The sham wrist bands had the button on the outside of the elastic band, and the button was worn facing away from the P6 point. Patients wore the wrist bands beginning the morning before chemotherapy and for six days after each cycle. Main outcome data were collected at baseline the day before chemotherapy and daily for up to seven days after chemotherapy, and additional data were collected on day 10. Some patients also participated in a qualitative interview.

• N = 361  
• AGE = Unable to determine
• MALES: 31.5%, FEMALES: 68.5%
• KEY DISEASE CHARACTERISTICS: Heterogeneous

• SITE: Multi-site    
• SETTING TYPE: Outpatient   
• LOCATION: United Kingdom

• PHASE OF CARE: Active antitumor treatment

Randomized, three-group, sham-controlled trial (Phase III)

• Rhodes Index of Nausea, Vomiting and Retching (INVR)
• MASCC Antiemesis Tool
• European Quality of Life-5 Dimensions (EQ-5D) utility scale
• Functional Assessment of Cancer Therapy—general quality of life scale
• Baseline measures—anxiety and depression, nausea/vomiting expectations, expectations from using the acupressure wrist bands

After the first cycle, there was no difference in the nausea level between any group, though there was a trend towards lower nausea scores for both the wrist band and sham wrist band groups. Qualitative interviews indicate that patients perceived both real and sham wrist bands as helpful in managing CINV.

Acupressure wrist bands are not an effective intervention in the management of CINV.

• Subject withdrawals ≥ 10%  
• Other limitations/explanation: 500 patients were randomized and data were only used on 361.

Nurses can educate patients that acupressure wrist bands are not an effective intervention to manage CINV.

To determine the effectiveness of acupressure in the management of chemotherapy-induced nausea and vomiting (CINV)

Patients were randomly assigned to one of three groups: use of P6 acupressure wristband, sham acupressure wristband, or usual care only. 

Prior to randomization, subjects were stratified by age group, gender, and emetogenicity of planned chemotherapy.  Patients were instructed to wear wristbands on both arms from the morning before chemotherapy administration and for the following 6 days, and to only remove them for showering or bathing. 

All patients received antiemetics based on American Society of Clinical Oncology (ASCO) and Multinational Association of Supportive Care in Cancer (MASCC) guidelines with the exception that NK1 receptor antagonists were not used with highly emetogenic chemotherapy, as these were not widely available in the country. 

All patients had rescue antiemetics available.  Study questionnaires were completed on day 10 of each cycle. Patients graded nausea daily.

• The study consisted of 372 patients.
• Two-thirds of the patients were over age 50. The sample included a few children. No other data was available.
• The majority (77.2%) of patients were female.
• A variety of tumor types and regimens were represented, with breast cancer as the most frequent.
• The majority of patients were receiving moderately emetogenic treatments.
• Almost all patients were Caucasian.

The study was conducted at multiple outpatient sites in the United Kingdom.

All patients were in active antitumor treatment.

This was a randomized controlled trial.

Measurement tools used were

• Rhodes Index of Nausea Vomiting and Retching
• MASCC Antiemesis Tool
• Functional Assessment of Cancer Therapy (FACT)-General
• The Hospital Anxiety and Depression Scale
• Patient expectations of nausea/vomiting, a two item, 11-point scale.

• The entire group showed relatively low levels of nausea. No significant differences were found between the three study groups in the experiences and measures of nausea; some improvement was found in both the actual and sham intervention groups. 
• The sham acupressure group had better odds ratio in improving nausea than the acupressure group. 
• No differences were found between groups in MASCC tool results for either acute or delayed nausea. 
• No differences were found in other outcome measures.
• Auditing of wristband use showed that compliance was good, with only four cases observed where use was incorrect. 
• Regression analysis showed that older age and male gender were predictive of better nausea outcomes (p = 0.005).

P6 acupressure was not shown to have a significant impact on prevention of CINV.  Findings suggest a potential placebo effect with both acupressure and sham acupressure wristbands.

• This study had unintended interventions or applicable interventions not described that would influence results.
• Participant withdrawals were 10% or more.
• No information about the use of any rescue medication was provided. 
• This study had very low nausea levels.

Findings did not show a significant effect of P6 acupressure on CINV; however, use of an actual and sham acupressure wristband may have a placebo effect.

To determine the feasibility and impact of providing a family-oriented intervention incorporating Hawaiian values on native Hawaiian women with cancer

Recruited patients were randomly assigned to an intervention or control group. The intervention group received sessions of informational and emotional support that incorporated prayer (often done by an elder), participant and staff disclosure of genealogies to affirm spiritual origins, and use of other cultural value items, such as graphics incorporating Hawaiian themes, plant fiber bags for program materials, and sharing of food. Sessions were focused on providing information on cancer basics and understanding of treatment and side effects, as well as information seeking and communication. Sessions included one or two patient-selected family members together. The intervention group had six sessions provided in a variety of locations, including homes, business offices, and libraries. Control group patients received two visits from the research team over three months and were provided with educational brochures and opportunity for having questions answered. Interventions were provided by master’s-prepared social workers.

• The sample included 12 participants.
• Mean age of patients was 55 years (intervention group range was 25–76 years; control group range was 48–84 years).
• Mean age of family members was 54 years.
• Patients were 100% female, and family members were 50% male.
• Patients had a variety of cancer types, including breast, ovarian, throat, uterine, lung, and lymphoma.
• Family members were primarily spouses and adult children.

Hawaii

A randomized prospective trial design was used.

• Cancer knowledge assessment (author developed)
• 12-item self-efficacy scale (author developed) (α = 0.91)
• Family Crisis-Oriented Personal Evaluation Scale (F-COPES)
• Brief Symptom Inventory (BSI)

In the intervention group, women showed significant improvement in F-COPES and decrease in BSI scores (p < 0.05). Family members also reported significant increase in self efficacy (p < 0.01) and F-COPES scores (p < 0.01). Women in the control group did not show change on any indicators, and their family members showed significantly poorer F-COPES total scores (p < 0.05).

Provision of a culturally relevant support intervention appeared to have a positive effect on Hawaiian patients and family members coping with cancer.

• The sample was small, with less than 30 participants.
• No specific diagnostic or symptom information was provided. Differences in these between groups can be expected to have substantial influence on outcomes of interest in this study.
• No demographic information was provided.
• No information regarding the stage of disease or phase of care was provided, another set of items that can be expected to influence outcomes.
• There was no appropriate attentional control, as control subjects received much less intervention time and content than the intervention group.

This study points to the need to consider provision of supportive interventions that are designed according to specific cultural values of participants. This particular study has a number of methodologic and reporting issues that limit the usefulness of findings.

To evaluate the use of Chinese herbal medicine as a complementary therapy for the reducing chemotherapy-induced toxicity

Patients were randomly assigned to one of three Chinese herbalists who evaluated and prescribed combination, single-item, packaged, herbal extract granules. Herbalists completed university training and were licensed to practice Chinese herbal medicine (CHM) in Hong Kong and China. Patients were randomly assigned to each group and received either CHM or placebo packages with corresponding serial numbers in a 14-day supply at each clinic visit. The placebo package contained nontherapeutic herbs with an artificial smell and taste similar to typical herb tea. Each patient completed the log for each day’s consumption. On days 1 and 14, patients met with the herbalist in the clinic setting for evaluation and the herbalist documented the visit in case report form. A quality-of-life questionnaire was completed at baseline, day 1 of each cycle, and after four months.

The sample consisted of 120 patients with early-stage breast and colon cancer receiving adjuvant treatment in a university-based cancer center in Hong Kong.

Patients were included in the study if they

• Were 18 years or older
• Had an Eastern Cooperative Oncology Group (ECOG) performance status of less than 2
• Had no prior chemotherapy
• Had normal hematologic, liver, and renal function.

Patients were excluded from the study if they

• Required concurrent radiotherapy
• Were unable to take or follow directions for daily oral medications
• Had evidence of distant metastasis
• Had concurrent medical illness
• Had received prior chemotherapy
• Were pregnant or breast feeding.

The study was conducted at a university-based cancer center in Hong Kong.

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

The National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 2.0 and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 were used.

Patients recorded their daily intake of the herbal package contents on patient logs. Herbalists documented patient visits in case report form 

• CHM was not found to be efficacious for reducing hematologic toxicity associated with adjuvant chemotherapy for breast and colon cancer.
• CHM did reduce grade 2 nausea in the CHM group compared to the placebo group.
• Accrual to the study was slow because patients had a preference for receiving the true CHM rather than participating in a controlled, placebo trial. Therefore, a formal interim analysis was conducted with only half of the target accrual. The review committee eventually terminated the study. 

• Patient accrual was difficult because the population believed CHM to be effective.
• Cost and storage is a barrier with the herbal or natural product granules.
• More than 225 different types of preparations are available.
• CHM requires use of trained and certified herbalists.

The objective of the study was to compare the efficacy and safety of 10% povidone-iodine and thoracoscopic talc insufflation for pleurodesis of recurrent malignant pleural effusions due to metastatic breast cancer.

Forty-two participants were randomized into two groups. Patients assigned to Group A received video-assisted thoracoscopic (VATS) drainage, mechanical adhesiolysis, and 4 g of talc poudrage, while the 20 patients assigned to Group B received VATS drainage, mechanical adhesiolysis, bedside pleurodesis with 20 mL of 10% povidone-iodine diluted in 30 mL of normal saline. Therapeutic thoracentesis was performed in all participants, and pleural fluid volume was recorded and sent for biochemical (pH, LDH, glucose), bacteriologic, and cytologic evaluation. All patients were scheduled for a follow-up every three months at which symptoms and chest x-rays were evaluated, and efficacy of pleurodesis was gauged on three levels: complete (absence of pleural fluid reaccumulation), partial (residual pleural fluid or reaccumulation that remained asymptomatic and not requiring thoracentesis), or failed (necessitating pleural procedures). Success was defined as a normal chest x-ray or radiologic reaccumulation of pleural fluid without recurrence of dyspnea or need for thoracentesis. Repeated ultrasound-guided thoracentesis was provided for patients with failed pleurodesis and reaccumulation of effusion at weekly intervals, and a PleurX^® catheter was offered for home management of effusions when required.

• The study reported on a sample of 42 patients.
• In Group A, the mean age was 48 years (SD = 9 years), and the range was 29–64 years.
• In Group B, the mean age was 50.2 years (SD = 7 years), and the range was 32–62 years.
• Data were not available to determine the percentage of males and females.
• Participants had malignant pleural effusion secondary to metastatic breast cancer.
• All patients either had either metastasis as their first presentation or had relapsed after chemotherapy during their follow-up.
• Patients were excluded from the study if they had a performance status greater than three, known allergies to iodine, a trapped lung, no change in the Medical Research Council (MRC) dyspnea scale after thoracentesis, pleural fluid pH less than 7.2 or glucose less than 60 mg/dL, and an extrathoracic metastasis.
• Both groups received the same protocol for adjuvant chemotherapy (i.e., 5FU, Adriamycin^®, and chlophosphamide (FAC), or docetaxel).
• No difference in preoperative demographic and clinical details between the two groups were noted.
   

This single-site study was conducted in an outpatient setting in the Department of Chest Medicine and Cardiothoracic Surgery in Cairo University Hospitals.
 

• Patients were in the transition phase after initial treatment.
• The study has clinical applicability for end-of-life and palliative care and late effects and survivorship.
   

The study was a prospective, randomized controlled trial.

• Medical Research Council (MRC) dyspnea scale to assess breathlessness
• Performance status scale (ECOG) to assess functional ability
• Diagnostic thoracentesis
   

Dyspnea and cough symptoms were improved in all patients after drainage and pleurodesis, and no mortality related to the procedure or perioperative mortality were observed. Survival rates between the two groups and totally at follow-up were 32 patients (76%) at eight months, 22 patients (52%) at two years, and 10 patients (23%) at four years. All had good outcomes with no bleeding complications and were discharged when both radiologic and clinical evidence confirmed complete resolution of pleural effusion. Group B experienced a significantly lesser post-procedural hospital stay (mean 5.7 days [SD = 2 days]) than Group A (mean 4.5 days [SD = 1.1 days]) (p = 0.009). During early follow-up in Group A, successful/complete response was achieved in 19 patients (87%), failure in 2 patients (9%), and partial response with radiologic reaccumulation at two months post-procedure but remaining asymptomatic during the 14 months’ follow-up. Early follow-up in Group B resulted in 17 (85%) complete response, no partial response, and three failures (15%) with recurrence of dyspnea at 33, 41, and 49 days respectively. No loculations were observed in Group B, thus a small-bore chest tube was placed and iodine was used again. In Group A, observed loculations were repeatedly aspirated with an ultrasound guide, and when repeated reaccumulation was experienced, an ultrasound-guided PleurX^® catheter was offered. No recurrence was detected at more than six months during follow-up, and no statistical difference between long-term success (four years) rates in Groups A (91%) and B (85%) were observed. Complications of pleuritic pain were observed in four participants of Group A (18%) but none in Group B, and fever was observed in four participants (18%) in Group A, and one participant (5%) in Group B.

Authors concluded that povidone-iodine pleurodesis is a safe and effective alternative to talc pleurodesis in the prevention of recurrent malignant pleural effusion at 30 days post-procedure. Additionally, while chest pain and fever are the most common adverse effects of pleurodesis, those in the iodine-povidone population (Group B) experienced less analgesic requirements and reports of fever, albeit at no statistical significance. Authors also emphasized that the dose of 10% povidone-iodine was administered in dilute form, thereby significantly increasing povidone safety with decreased toxicity when compared to other studies.

• The study had a small sample size, with less than 100 participants.
• The study results are only significant to a population of patients with malignant pleural effusion secondary to metastatic breast cancer; more research is warranted for efficacy among other population types.
• The clinical practice of providing mechanical adhesiolysis through the VATS procedure may have contributed to successful pleurodesis in both groups; true translation of this evidence would require performing a VATS procedure prior to the instillation of povidine-iodine, which is an uncommon practice. (Patients usually have a VATS procedure with talc insufflations or a chest catheter bedside procedure but not a surgical procedure followed by a bedside procedure.)
• Statistical analysis was limited by a lack of computed confidence intervals to safely exclude clinically relevant differences, as well as a lack of survival analysis.
   

Given its good success rate and fewer complications, povidone-iodine appears to be a successful, safe, and cost-effective alternative to talc pleurodesis for palliative management of malignant pleural effusion stemming from metastatic breast cancer.

The aim of the study was to evaluate the value of glutamic acid as a modifier in vincristine-induced neurotoxicity.

Children were randomized to treatment or placebo groups during adjuvant treatment with vincristine. Patients were evaluated weekly by physical examination. The treatment group received glutamic acid 1.5 g orally per day in three divided doses during a four-week induction with vincristine.

• The sample consisted of 94 pediatric patients (72% male and 28% female) with a mean age of 7.1 years (range of 3–18).
• The patients had acute lymphoblastic leukemia, non-Hodgkin lymphoma, or Wilms tumor.

The study was conducted at a single site in Egypt.

Phase of Care

• Active antitumor treatment

Clinical Applications

• Pediatrics
   

The study had a double-blind, randomized, placebo-controlled design.

• Achilles tendon reflex and patellar reflex were graded as normal, decreased, or absent.
• Parasthesis was recorded as absent, mild, moderate, and severe.
• Strength was assessed as normal, mild decrease, moderate decrease, and severe decrease.
   

Achilles and patellar reflexes were decreased at weeks 3 and 4 in more patients receiving placebo. Prevalence of mild parasthesias was greater in the placebo group at week 4. No severe parasthesias were recorded in the glutamic acid group compared to an incidence rate of 7.5% in the placebo group. The differences were not statistically significant.

The findings suggest that glutamic acid may be helpful in reducing vincristine-induced peripheral neuropathy symptoms in pediatric patients.

• Limitations include the small sample size (less than 100), measurement validity and reliability, and the findings not being generalizable.
• The method of grading reflexes and symptoms was not shown to be reliable, and physical examinations and grading were done by different physicians.
• Although the article states that patients were randomly assigned, it also states that the oncologist decided on the treatment, so assignment method is unclear.
• It is not stated whether there were any chemotherapy dose adjustment or delays.
• The article notes that “other treatments” were at the physician's discretion, so it is unclear if only glutamic acid was given for neuropathic effects.

 The findings suggest that glutamic acid may be helpful in managing peripheral neuropathy from vincristine; however, several study limitations exist. Additional well-designed research in this area is warranted.

To compare celecoxib versus diclofenac in mild to moderate depression in patients with breast cancer

Patients with breast cancer with mild to moderate depression and pain were randomized to receive celecoxib or diclofenac over a six-week period. Depression was evaluated at baseline, three weeks, and six weeks.

• N = 52
• MEAN AGE: 18-70 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Patients had breast cancer for more than 100 days; major depression according to ​Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR), 4th edition; a score of less than or equal to 18 on the Hamilton Depression Rating Scale (HDRS); and mild to moderate pain, and needed an analgesic.
• OTHER KEY SAMPLE CHARACTERISTICS: No other psychotropic medication and no behavioral intervention therapy.

• SITE: Single site
• SETTING TYPE: Outpatient
• LOCATION: Tehran, Iran

• Single center, double-blind, controlled, parallel group

• DSM-IV-TR to diagnose
• HDRS
• Visual Analog Scale (VAS) mild to moderate pain (0-100) measured by need for analgesic

Fifty-two patients randomized with similar characteristics showed a significant reduction in HDRS score in celecoxib group by week six; however, none achieved a remission of symptoms. There was no significant difference in VAS score.

There was a greater antidepressant effect for celecoxib than for diclofenac by week 6.

• Small sample (less than 100)
• Risk of bias (no control group)
• Findings not generalizable
• Very short time frame; metastatic disease may have had an effect on results due to pain and prognosis

It is important to recognize that symptoms often present in clusters (pain/depression), and treatment of all symptoms are important to often achieve relief of any symptom.