To evaluate the efficacy of megestrol acetate versus dronabinol, as well as a combination of these treatments

This was a randomized, controlled, three-arm trial using a double-blind procedure. The first arm evaluated the efficacy of 800 mg/day of oral megestrol acetate plus a capsule placebo; the second arm evaluated the efficacy of 2.5 mg of oral dronabinol twice daily plus a liquid placebo; and the third arm combined both medications. Evaluations were taken at noted doses.

The final sample included 469 patients. The sample was stratified for confounding factors, including age, gender, cancer type, estimate of survival, performance status, severity of weight loss, concomitant radiation therapy, treatment center, and planned or ongoing treatment. Sample size calculations included a power analysis and accounted for attrition.

All participants shared the following characteristics:

• Adults with an incurable malignancy, with the exception of brain, breast, ovarian, and endometrial cancers 
• An estimated life expectancy of three months or more, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2 
• A self-reported weight loss of at least five pounds and/or physician-estimated caloric intake of 20 or fewer calories/kg of body weight/day.

North Central Cancer Treatment Group (NCCTG) trial involving 20 NCCTG institutions, including the Mayo Clinic

A double-blind, randomized controlled trial design was used.

• Weight was measured using home scales and office scales.
• Anorexia was assessed using validated NCCTG questionnaires.
• Quality of life was assessed using a single-item Uniscale and a 13-item, anorexia-specific Functional Assessment of Anorexia/Cachexia Cancer Therapy (FAACT) instrument. The validity and reliability of these instruments was previously reported.

No differences between groups at baseline were noted. A greater percentage of patients treated with megestrol acetate reported appetite improvement (75% versus 49%; p = 0.0001) and baseline weight gain (11% versus 3%, p = 0.02) for ≥ 10%) compared with dronabinol-treated patients. Combination treatment conferred no additional benefit.

FAACT demonstrated improved quality of life among megestrol acetate–treated and combination-treated patients. Uniscale scores were similar for both groups. Toxicity among groups was comparable, with the exception of a greater incidence of impotence among men who received megestrol acetate.

• The study lacked a constitutive definition of anorexia.
• Eligibility criteria used self-reported weight loss and physician estimates of caloric intake.
• Outcome measures used weight measurement in the oncologist’s office; accuracy and precision of the scale used to assess weight were not explicated.
• Validity and reliability of instruments was not included.
• Recruitment sites were listed, but these settings were not described.
• Cost implications were not discussed.

To evaluate the efficacy of ecosapentaenoic acid (EPA) supplement plus placebo versus megestrol acetate plus placebo supplement versus combination of both EPA supplement and megestrol

The EPA dose was 1.09 g BID in supplement plus liquid placebo. The megesterol acetate dose was 600 mg/day plus placebo supplement BID. The combination dose was EPA 1.09 g supplement BID plus megesterol acetate 600 mg/day. Patients were stratified and randomized to one of three treatment arms. Median number of days on study was relatively equal for all three arms at slightly more than three months. Megesterol acetate served as the control arm secondary to its proven efficacy.

• The study reported on 421 patients.
• Inclusion was based on age 18 years or older with incurable malignancy other than brain, breast, ovarian, prostate, or endometrial cancer; life expectancy of three months or more; Eastern Cooperative Oncology Group performance status of 2 or better; and self-reported two-month weight loss of five or more pounds and/or physician-estimated daily intake of less than 20 calories/kg/day.
• All patients had to perceive that weight loss was a problem, and the physicians had to view weight gain as a beneficial outcome.
• Exclusion criteria other than previously listed tumor types were use of tube feedings or parenteral nutrition; edema or ascites; use of adrenal steroids (other than short-term dexamethasone with chemotherapy), androgens, progestational agents, or other appetite stimulants within the past month; brain metastases; insulin-requiring diabetes; pregnancy; lactation; poorly controlled hypertension or congestive heart failure; history of thromboembolism; and obstruction in alimentary tract, malabsorption, or intractable vomiting.

The study was a collaborative effort of the North Central Cancer Treatment Group (NCCTG) and the National Cancer Institute of Canada, conducted at 26 primary treatment centers.

A double-blinded, randomized, three-armed trial design was used.

• Weight measured at MD’s office at baseline and monthly
• NCCTG questionnaire to measure appetite and weight loss at baseline, weekly, for four weeks, and then monthly 
• Functional Assessment of Anorexia/Cachexia Therapy (FAACT) administered at same intervals as above
• Single-item uniscale question to measure global quality of life administered at same intervals as above

The primary endpoint was weight gain of 10% or more (chosen because of previously proven efficacy of megesterol acetate). Among the three arms, 6% of patients achieved this in the EPA arm, 18% in the megesterol arm, and 11% in the combination arm. There was a p value of 0.01 showing greater efficacy with single-agent megesterol acetate. Appetite results using the NCCTG questionnaire were comparable for all three groups, showing varying degrees of favorable effects in all treatment arms. Appetite results using FAACT showed that the megesterol acetate and combination arms provided better appetite stimulation than EPA alone: 40 for EPA, 55 for megesterol acetate, and 55 for combination.

There was no significant difference for survival times or quality of life between the three arms. Recommendation of authors is not to use EPA alone or in combination.

Sample size was very good, and statistical analysis was very thorough.

• The study did not include a true placebo arm; therefore, the orexigenic effects of EPA cannot be determined but rather only suggested since there was an equivalent result on the NCCTG questionnaire when compared to megesterol acetate.
• No definition of anorexia was provided.

To determine whether sunscreen prevents or mitigates epidermal growth factor receptor–inhibitor (EGFRI)-induced rashes.

Patients were stratified based on (a) first-line cancer therapy versus other therapy, (b) type of EGFRI prescribed or anticipated (e.g., small molecule inhibitor versus monoclonal antibody), and (c) use of a concurrent medication that increases sun hypersensitivity.   

Patients were randomly assigned to sunscreen with a sun protection factor (SPF) of 60 to be applied to the face, trunk, and extremities BID for 28 days versus an identical-appearing  placebo. The sunscreen included 7.5% titanium dioxide and 7.5% zinc oxide, and was shown to block more than 90% of both ultraviolet A and ultraviolet B light in preclinical trials. All patients were instructed to stay indoors or in a covered area from 10 AM to 3 PM to avoid peak sun exposure. 

• The study reported on a final sample of 89 patients. Initially, 54 patients were in the sunscreen arm and 56 patients were in the placebo arm.
• Median patient age was 63 years (range 36–90) in the sunscreen arm and 62 years (range 37–88) in the placebo arm.
• The sample was 54% female and 46% male in the sunscreen arm, and 52% female and 48% male in the placebo arm.
• In the sunscreen arm, 22 patients (41%) had lung cancer, 22 patients (41%) had gastrointestinal cancer, and 10 patients (19%) had another type of cancer. In the placebo arm, 17 patients (30%) had lung cancer, 23 patients (41%) had gastrointestinal cancer, and 16 patients (29%) had another type of cancer.
• EGFRI characteristics were as follows. In the sunscreen arm, 21 patients (39%) received erlotinib (or another small molecule inhibitor) and 33 patients (61%) received cetuximab (or another antibody). In the placebo arm, 22 patients (39%) received erlotinib (or another small molecule inhibitor), and 34 patients (61%) received cetuximab (or another antibody).

• Multi-site
• Outpatient clinic
• United States

Patients were undergoing the active treatment phase of care.

This was a placebo-controlled, double-blind trial.

• History and physical (baseline, end of week 4, and end of week 8)
• Performance status score (baseline, end of week 4, and end of week 8)
• Brief rash incidence questionnaire (weekly for eight weeks)
• Skindex-16 (quality-of-life tool) (weekly for eight weeks)
• Previously used questionnaire on patient compliance with EGFRI therapy (weekly for eight weeks)
• National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (end of week 4 and end of week 8)

• During the four-week intervention, physician-reported rash occurred in 38  patients (78%) in the sunscreen arm and 39 patients (80%) in the placebo arm (p = 1.00). No statistically or clinically significant differences existed in physician-reported rash severity or patient-reported outcomes of rash. Adjustments for sun intensity by geographical zone, season, and use of photosensitivity medication did not yield a significant difference in rash across the study arms (p = 0.2). 
• The patient-reported Skindex-16 questionnaire did not reveal major differences between the study arms. Quality-of-life scores declined but remained comparable between arms. 
• The sunscreen was well tolerated with low and almost identical rates of adverse events in the two study arms.
   

The use of sunscreen (SPF of 60) did not prevent or decrease the severity of EGFRI-induced rash.

• The sample size was fewer than 100 patients. 
• No tool was available to measure the actual degree of sun exposure for each patient.  
• The generalizability of the results is limited. This study primarily included patients who were receiving erlotinib or cetuximab. Other small molecule inhibitors (e.g., lapatinib) and monoclonal antibodies (e.g., panitumumab) exist, and patients receiving those drugs might respond to sunscreen differently.
• Patients were not to be in the sun from 10 AM to 3 PM, so their sun exposure was greatly limited. In addition, actual patient compliance with avoidance of sun exposure and application of sunscreen or placebo was not evaluated or reported.

No evidence existed to support the use of sunscreen to prevent or decrease the severity of EGFRI-induced rash.

STUDY PURPOSE: To evaluate evidence for psychological interventions in women with breast cancer

TYPE OF STUDY: Meta analysis and systematic review

PHASE OF CARE:  Multiple phases of care

In 24 of 28 trials, cognitive behavioral therapy was the basis of the intervention. Most studies had unclear risk of bias, and for studies aimed at anxiety and depression, quality of the evidence was graded as low. Comparison of CBT versus control across multiple studies for depression showed an overall standard mean difference (SMD) of -1.01 (p = 0.02) in favor of the CBT intervention. Only two studies examined CBT delivered individually, showing no significant benefit and high heterogeneity. Examined separately, group CBT also did not consistently show significant benefit for depression. Eight studies looked at change in anxiety. Both individual- and group-delivered CBT showed significant benefit, with an overall SMD -10.48 (p = 0.0006). CBT showed a significant positive effect for stress, and only marginal effect on quality of life.

Findings showed overall benefit of CBT for anxiety and depression in women with early-stage breast cancer

Although studies have shown that psychological interventions are more effective for individuals with psychological problems, the studies included here excluded women with psychological morbidity.  There was high heterogeneity, and most studies were of low quality.

CBT delivered in a group or individual setting has been shown to have a positive effect on depression and anxiety among women with early-stage breast cancer. The strength of these results is limited by the relatively low quality of studies included in this review.

• The author described strategies to prevent or minimize symptoms of palmar-plantar erythrodysesthesia (PPE).
  • Dose reduction or interruption of therapy often is necessary.
  • Use a systemic strategy.
  • Pyridoxine has been found beneficial as therapy (doses of 50–150 mg per day).
  • High-potency corticosteroids and a wet disinfectant treatment of blisters and erosions have been effective as local topical therapy. For grade 1 PPE, avoiding mechanical irritation of the skin on the palms and soles and mild emollient creams are sufficient. Cooling the affected areas with a cooling battery or hand and foot baths (without extensive washing) may relieve the symptoms.

Multiple interventions can be implemented to prevent or minimize PPE, including teaching patients to avoid mechanical irritation of the skin, use topical emollient creams, and use regional cooling.

• Patients received 910 mg/m² IV amifostine as a 15-minute infusion prior to 200 mg/m² melphalan.
• Ten consecutive patients who were treated within the same protocol without amifostine were used as controls.
• Patients received granulocyte colony-stimulating factor (G-CSF) from day +4 to neutrophil recovery.

• The study reported on a sample of 20 patients.
• All patients were receiving 200 mg/m² high-dose melphalan and autologous stem-cell transplant (ASCT).
• Patients were given cytoxan, mesna and G-CSF for mobilization.

The study was conducted between November 1998 and February 2000.

This was a pilot, feasibility study.

The National Cancer Institute (NCI) Common Toxicity Criteria for Oral Mucositis was used to assess oral mucositis daily.

Most of the patients (9 out of 10) received the full dose of amifostine. One patient received only 780 mg/m² because of recurrent hypotension. Significant nausea, as well as hypotension and vomiting, occurred.

Amifostine did not show a benefit for gastrointestinal toxicity or mucositis of more than grade 2.

• This was a feasibility study.
• The sample size was small.

To evaluate the efficacy of ramosetron, aprepitant, and dexamethasone in preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving cisplatin-based chemotherapy

On day 1, all patients received intravenous 0.6 mg ramosetron and oral 12 mg dexamethasone 30 minutes before chemotherapy, and they received 125 mg aprepitant orally one hour before chemotherapy. On days 2 and 3, patients received 80 mg aprepitant and 8 mg dexamethasone orally in the morning. On day 4, patients only received 8 mg dexamethasone. Patients could take rescue antiemetic medications at any time for vomiting or severe nausea. Antiemetic rescue medications were determined by treating physicians.

• N = 39  
• MEDIAN AGE = 59 years (range = 43–74 years)
• MALES: 75.6%, FEMALES: 24.4%
• KEY DISEASE CHARACTERISTICS: Multiple types of cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Both adjuvant and palliative chemotherapy (primarily palliative)

• SITE: Multi-site    
• SETTING TYPE: Outpatient    
• LOCATION: Korea

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Palliative care 

Prospective, open-label study

• Complete response (no vomiting and no rescue medications divided into acute phase [0–24 hours], delayed phase [24–120 hours], and overall phase)
• Absolute complete response (no vomiting, no rescue medications, and no nausea) 
• Multinational Association of Supportive Care in Cancer Visual Analog Scale (MASCC VAS)
• Common Toxicity Criteria for Adverse Events (CTCAE) clinical and laboratory adverse events

Complete response (CR) was achieved by 94.9% of patients in the acute phase, 92.3% in the delayed phase, and 92.3% in the overall phase. Absolute CR was achieved by 74.4% in the acute phase, 51.3% in the delayed phase, and 46.2% in the overall phase. The median nausea score during the acute phase was 0 (interquartile range [IQR] 0–1), 0 in the delayed phase (IQR 0–4), and 2 during the overall phase (IQR 0–4). On the VAS, mild nausea was observed in 10% of patients in the acute phase and 13% of patients in the delayed phase. Moderate to severe nausea was observed in 15% of patients in the acute phase and 36% of patients in the delayed phase.

The combination of ramosetron, aprepitant, and dexamethasone is an effective CINV regimen. The overwhelming majority of patients in this study achieved a complete response and experienced no nausea or vomiting in both the acute and delayed phase after chemotherapy.

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

Ramosetron, aprepitant, and dexamethasone is an effective regimen to prevent CINV in patients receiving cisplatin-based therapy. Almost all of the patients were able to achieve a complete response in both the acute and delayed phase after administration of chemotherapy. In this study, the majority of patients were receiving palliative care, therefore this combination of drugs should be considered for palliative care patients.

To investigate the effect of a combined hatha and restorative yoga intervention on memory in cancer survivors and to explore relationships between memory and sleep

YOCAS^©® (Yoga for Cancer Survivors) is an instructor-guided standardized program that incorporates movement emphasizing restorative poses, breathing exercises, and mindfulness exercises. The intervention was offered twice a week in the late afternoon or evening over 75 minutes for a total of eight sessions. Although all the group trainers were Registered Yoga Alliance Teachers, they were also required to complete a training session, reviewing a detailed YOCAS^©® manual to facilitate standardization across sites.

• N = 328   
• MEAN AGE = 54.62 years
• AGE RANGE = 26–72 years
• MALES: 4%, FEMALES: 96%
• CURRENT TREATMENT: Hormonal therapy in 53% of sample
• KEY DISEASE CHARACTERISTICS: Various cancers but predominantly breast cancer (77%)
• OTHER KEY SAMPLE CHARACTERISTICS: Of the sample, 82% had a partial college education or more. Seventy-four percent of women were postmenopausal.

• SITE: Multi-site  
• SETTING TYPE: Outpatient    
• LOCATION: 12 cities within the United States

PHASE OF CARE: Late effects and survivorship

Secondary analysis of a randomized, clinical trial

• MD Anderson Symptom Inventory (MDASI)—primary outcome was one item regarding perceived memory.
• Pittsburgh Sleep Quality Index (PSQI)—primary outcome was global sleep quality.

At baseline, the average score on the MDASI indicated only a mild level of perceived memory problems overall. Although both groups continued to report memory problems as being mild, a significant decrease (p < 0.05) was observed in patients who completed the intervention. This difference continued to be significant when controlling for differences in age, gender, educational level, past treatment regimen, current hormonal therapy, baseline memory, and baseline sleep scores. Of note, those who received the intervention also had improved sleep (p < 0.05), which accounted for approximately 26% of the improvement in memory (p = 0.039).

Although yoga appeared to decrease perceived memory problems, this outcome was based on a single item of the MDASI. Further longitudinal studies designed specifically to measure the effect of yoga on cognitive function as measured by both objective and subjective measures are warranted.

• Risk of bias (no blinding)
• Measurement validity/reliability questionable

Although this study suggested that yoga may improve patients’ perception of memory problems, some of the benefit was because of better sleep.

To compare the efficacy of massage therapy to a social attention condition in Taiwanese patients with cancer with bone metastases

• A five-day, two-group trial with a pre/post-test design was used.
• The experimental intervention was 45 minutes of massage; condition control was caring therapist for a comparable amount of time.

• The sample was 72 patients with cancer with bone metastasis.
• Mean patient age was 50 years.
• The sample was 42% male and 58% female.
• The sample was Taiwanese, age 18 or older, oriented x3 (alert and normal), Chinese-speaking and reading, radiologically diagnosed with bone metastasis via bone scan, and reporting moderate bone pain of at least 4 on a 0–10 scale.
• Patients were excluded if they were regularly receiving massage therapy, were undergoing surgeries or procedures during admission, or had allodynia, thrombocytopenia, spinal cord compression syndrome, deep vein thrombosis, or other contraindications to massage therapy.

• Single site
• Inpatient setting
• Five hospital oncology units

• Patients were undergoing the active treatment phase of care.
• The study has clinical applicability for end-of-life and palliative care.

The study was a randomized, controlled clinical trial.

• Present Pain Intensity (PPI) – Visual Analog Scale (VAS)     
• Mood VAS
• Relaxation VAS
• Sleep VAS
• Symptom Distress Scale
• Demographic and medical profiles

• Pre- to postintervention effects: No statistical significance was shown in individual patients.
• Results from MANCOVAs showed statistically significant intervention effects on pain, mood, and relaxation VASs, but not the sleep VAS.
• There was a significant linear group by time effect on relaxation VAS in both groups: F (1, 69) = 10.39, p = 0.002, indicating a different pattern of change in relaxation VAS change scores between the groups.

This trial documented therapeutic effects of massage on improving pain intensity, mood status, and muscle relaxation in patients with metastatic bone pain. The study has clinical implications supporting massage therapy and other medical modalities for optimal improvement in patients with cancer with bone metastases.

• The study had a small sample, with less than 100 participants.
• The patient population was heterogeneous.
• The study involved a short course of therapy.
• The study lacked multidimensional measurement of pain and patient binding.

Massage therapy may play an important role in cancer bone pain, sleep, and, mood.

• FINAL NUMBER STUDIES INCLUDED = 5
• TOTAL PATIENTS INCLUDED IN REVIEW = 415
• SAMPLE RANGE ACROSS STUDIES: 66–93 patients
• KEY SAMPLE CHARACTERISTICS: Mean age = 54.5 years; mean weight = 73.9 kg; mean height = 169 cm; predominantly Caucasian

PHASE OF CARE: Multiple phases of care (not reported)
 
APPLICATIONS: Palliative care

No head to head trials between products existed. FBT produced a greater improvement in PID in the first 60 minutes after dosing (66% more probable than ODT and 68% more than OTFC). ODT and OTFC showed similar benefits, and ODT had a slightly higher benefit with a 53% probability of pain relief at 60 minutes. The two agents compared with morphine sulfate immediate-release, FBT and ODT, were compared, and benefits were significant within 15 minutes after dosing.

FBT may be advantageous as a fentanyl product, as it showed an advantage over ODT and OTFC.

Two of the trials compared FBT to a placebo, so more paitents received FBT. Therefore, cell sizes were not similar, resulting in an unequal comparison. Seven transmucosal immediate-release fentanyl (TIRF) studies existed. Only three were used in the comparison. Limited databases were searched.

Some TIRF products may have better efficacy compared to others. This analysis showed that FBT had an advantage. All products were shown to be superior to morphine in achieving pain relief one hour after dosing. Additional head to head comparison studies are needed.