To evaluate the safety and efficacy of thalidomide in attenuating weight loss in patients with cachexia secondary to advanced pancreatic cancer

Fifty patients were randomized to receive 200 mg of thalidomide by mouth daily or placebo for 24 weeks. At four weeks, 33 patients were evaluated; at eight weeks, 20 patients were evaluated.

Patients were included in the study if they

• Had inoperable pancreatic cancer
• Experienced 10% weight loss over the preceding six months
• Had a life expectancy of at least six weeks.

Patients were excluded if they

• Had received any form of antineoplastic treatment in the preceding six weeks
• Weighed less than 40 kg
• Concurrently used steroids, anabolic drugs, hormonal agents, or appetite stimulants
• Were younger than 18 years of age
• Had peripheral neuropathy
• Had severe constipation.

The study was a randomized, placebo-controlled trial.

• Primary outcome: Change in weight at four weeks
• Secondary outcomes:
  • Change in bone and free muscle mass
  • Grip strength
  • Quality of life (physical performance and global health status)
  • Survival

At four weeks, 33 patients were evaluable. The thalidomide arm gained 0.37 kg in weight and 1 cm³ of arm circumference muscle mass. The placebo arm lost 2.21 kg in weight and 4.46 cm³ of arm circumference muscle mass.

At eight weeks, 20 patients were evaluable. The thalidomide arm lost 0.06 kg in weight and 0.5 cm³ of arm circumference muscle mass. The placebo arm lost 3.62 kg in weight and 8.4 cm³ of arm circumference muscle mass.

Thalidomide was well tolerated and effective at attenuating weight loss and loss of lean body mass. Findings were unable to demonstrate that attenuation in weight loss led to improvement in quality of life.

• The study had a high attrition rate: 70% were evaluable at four weeks, and 43% were evaluable at eight weeks.
• Baseline weight in the control group was 4 kg lighter.
• Change in appetite was not measured as a primary outcome.

To demonstrate the efficacy, safety, and acceptability of intranasal sufentanil as a treatment for cancer-related breakthrough pain (BTP)

Dose titration included three steps. In step 1, a clinician administered 9 mcg sufentanil. Administration was repeated at 10 and 20 minutes, as  required. If sufentanil was ineffective at 30 minutes, the clinician administered, the patient's usual BTP opioid. Step 2 comprised actions relating to the next episode of BTP. During this episode, the clinician administered 18 mcg sufentanil, using the same repetition procedure as in step 1. In step 3, during the next episode of BTP, the clinician administered 36 mcg sufentanil, using the same repetition procedure as in step 1. In all steps, pain was assessed at 0, 5, 10, 15, 30, 60, and 120 minutes. In the ongoing phase of the study, in each BTP episode, each patient received the titrated dose that had proven effective.

• The sample was composed of 30 patients. The study comprised 64 BTP episodes.
• Authors did not report information about patients' ages.
• Authors did not report information about the gender of patients.
• The sample comprised patients who had cancer, were not opioid naive, showed clinical evidence of opioid responsiveness, and were taking stable doses of long-acting opioids. The sample included 11 cases of neuropathic pain, 7 of visceral pain, 6 of somaic pain, 5 of mixed pain, and one of pain of an unknown type. No patient died during the study.

• Multisite
• Inpatient
• Three palliative care units in Australia

Prospective, descriptive study

• Verbal rating, on a 0–10 scale, of percentage of pain intensity difference (%PID)
• Respiratory rate
• Oxygen saturation
• Presence or absence of nausea, vomiting, confusion, nasal pain, or nasal bleeding
• Drowsiness scale (0 = none, 4 = unarousable)

• Median verbal rating of PID at baseline was 5.5, mean rating was 5.9 (SD = 1.8); median verbal rating of PID at 15 minutes was 3, mean rating was 3.3 (SD = 2.3) (p < 0.0001); median verbal rating of PID at 30 minutes was 2, mean rating was 2.5 (SD = 2.4) (p < 0.0001).
• The %PID was greater than 33% at 30 minutes, by which time 40 of 64 patients (63%) had responded to treatment.
• Dose range was 9–108 mcg. Median dose was 18 mcg.
• Of 30 participants, 23 rated intranasal sufentanil as better than usual medications.
• Four of 64 patients (6%), reverted to usual BTP medication after 30 minutes.
• Authors found no correlation between baseline opioid dose and the dose that was effective in treating BTP.
• In three episodes the drowsiness score was higher than 2. In two patients, the adverse effect was nausea. In one patient, the adverse effect was headache.

The study showed that intranasal sufentanil has rapid onset and is an effective and safe means of controlling cancer-related BTP.

• The study had a small sample, with fewer than 100 patients.
• Authors did not provide a definition of effective pain relief.
• Authors did not provide demographic information.

Sufentanil may be an option for the treatment of BTP; presently, however, its use remains investigational.

Southwest Oncology Group Study 9626 evaluated  megestrol for management of menopausal symptoms in women with breast cancer. It compared two doses of megestrol acetate  versus placebo over six months. Participants were randomized to placebo, megestrol 20 mg, or megestrol 40 mg daily for three months. If success was achieved, treatment continued for three additional months. If not, the patient was unblinded and given megestrol 20 mg daily.

Participants: 288 patients with T 1-3, N0-1 breast cancer following surgery, chemotherapy, and at least four months of tamoxifen, if prescribed, were enrolled. 225 completed the trial.

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

At the initial evaluation, patients completed a seven-day patient daily log of hot flashes with re-evaluation at three and six months. The primary endpoint was differences in the probability of hot flash reduction in three comparison groups.  Instruments included:

• The patient report of menopausal symptoms
• The symptom log
• National Cancer Institute Common Toxicity Criteria, version 2.
• Performance status assessed using ECOG scale

At three months, improvement was 14% with placebo, 65% withmegestrol acetate 20 mg, and 48% with megestrol acetate 40 mg. Both doses were superior to placebo (p < .0001). Duration of effectiveness continued at six months. Megestrol 40 mg was not superior to megestrol 20 mg.

The recommended daily dose is 20 mg.

The study was not designed to evaluate long-term toxicities or relapse of symptoms with long-term use. Concern remains regarding the use of progestins in women with a history of breast cancer.

To determine if there is sufficient evidence that pre-emptive antifungal treatment is as effective as antifungal prophylaxis with posaconazole. The patient populations addressed included patients with acute myelogenous leukemia or myelodysplastic syndrome with prolonged chemotherapy-induced neutropenia and allogeneic hematopoietic stem cell transplantation (HSCT) recipients with significant graft-versus-host disease.

Prophylactic antifungal therapy is defined as the initiation of an antifungal agent to high-risk patients to prevent a fungal infection. Pre-emptive antifungal therapy is defined as the initiation of antifungal therapy in high-risk patients based on laboratory markers, radiologic monitoring, or both to identify early ​invasive fungal infections (IFIs) before clinically overt disease develops. The authors based their evaluation on the principle that prophylaxis of fungal infections is important due to the significant morbidity and mortality associated with fungal infections, the incidence in high-risk patients, the safety of available antifungal agents, and the lack of sensitive methods of early detection. A pre-emptive approach is limited by the sensitivity and specificity of available detection methods. The authors reviewed the current literature on posaconazole prophylaxis and pre-emptive antifungal therapy.

No databases used for a search were listed, nor were any inclusion or exclusion criteria mentioned. However, keywords searched were invasive fungal infection, prophylaxis, pre-emptive therapy, and aspergillosis.

One prospective, randomized trial compared posaconazole with fluconazole or itraconazole as a primary antifungal prophylaxis in patients with acute myelogenous leukemia or myelodysplastic syndrome with prolonged chemotherapy-induced neutropenia. Proven or probable IFIs occurred in seven (2%) patients in the posaconazole group and 25 (8%) patients in the fluconazole or itraconazole group (p < 0.001). Significantly fewer patients in the posaconazole group had invasive aspergillosis. Survival was improved in posaconazole recipients (p = 0.04). Serious adverse events possibly related to treatment occurred in 6% of patients in the posaconazole group and in 2% in the fluconazole or itraconazole group (p = 0.01).

One prospective, randomized trial compared primary antifungal prophylaxis with posaconazole versus fluconazole in allogeneic HSCT recipients with significant graft-versus-host disease on immunosuppression. Posaconazole was at least as effective as fluconazole in preventing IFIs during the prespecified period of observation (incidence, 5.3% versus 9%, respectively; p = 0.07) but was superior in preventing invasive aspergillosis and deaths caused by IFIs. If the analysis was restricted to the period in which patients received the study drug, posaconazole was considered superior to fluconazole in preventing IFIs (incidence, 2.4% versus 7.6%; p = 0.004), particularly invasive aspergillosis (incidence, 1% versus 5.9%; p = 0.001). Treatment-related adverse events were similar between the groups. One peer-reviewed publication reported pre-emptive antifungal therapy. The study was a feasibility study in which a total of 136 treatment episodes for patients with neutropenia at high risk for IFI were screened with daily serum galactomannan testing. There was a diagnostic algorithm that included chest computed tomography (CT) scans and bronchoalveolar lavage. Patients who met prespecified criteria for probable or proven invasive fungal infection received pre-emptive therapy with liposomal amphotericin B; neutropenic fever alone did not trigger modification in the antifungal regimen. Although this approach was successful in identifying early invasive aspergillosis and avoiding amphotericin B use in most patients with persistent neutropenic fever of unknown origin, invasive aspergillosis developed in 17 patients and zygomycosis in one patient among 136 chemotherapy treatment episodes. All cases of invasive aspergillosis were identified through positive antigenemia results. Seven (41%) deaths occurred in patients with positive serum galactomannan results; of these, six had autopsy-proven invasive aspergillosis. However, only two patients were considered to have died directly because of invasive aspergillosis.

The authors believe that insufficient evidence exists to recommend a pre-emptive antifungal therapy approach in place of posaconazole prophylaxis in patients with acute myelogenous leukemia or myelodysplastic syndrome with prolonged chemotherapy-induced neutropenia and allogeneic hematopoietic cell transplantation (HCT) recipients with significant graft-versus-host disease.

No conflict of interest was stated.

Posaconazole is recommended as a primary antifungal prophylaxis in patients with acute myelogenous leukemia or myelodysplastic syndrome with prolonged chemotherapy-induced neutropenia and in allogeneic HCT recipients with significant graft-versus-host disease. Pre-emptive treatment is not recommended in these patient populations.

To assess the effectiveness of and adverse events associated with opioid rotation for the management of cancer-related pain

All consecutive patients who attended the clinics of participating hospitals were eligible. A single opioid conversion table was used by all participants. If a rotation was used because of pain and toxicity, the baseline dosage was reduced by 25%–50% prior to the change. If no toxicity was present, an equivalent dose was used. Pain was assessed days prior to the implementation of the rotation and one week postimplementation. During the week, changes in opioid dosage were allowed and recorded. Patients were followed for 90 days.

• N = 67  
• MEDIAN AGE = 61 years (range 27–91 years)
• MALES: 73.1%, FEMALES: 26.9%
• KEY DISEASE CHARACTERISTICS: Various tumor sites; lung cancer was most prevalent; most had advanced disease
• OTHER KEY SAMPLE CHARACTERISTICS: Pain was nociceptive in 53.6% and mixed or neuropathic in 46.3%

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

• PHASE OF CARE: Late effects and survivorship
• APPLICATIONS: Palliative care 

Observational

• Numeric Rating Scale (NRS) for average and breakthrough pain
• Number of breakthrough episodes per day
• Common Terminology Criteria for Adverse Events (CTCAE)

About 89.5% of patients had one opioid rotation. The most common drugs used for the rotation were morphine, fentanyl, and transdermal buprenorphine. The most common switch was from fentanyl to morphine. The rotation was effective in 75.4% of patients for reducing average pain and in 57.8% for breakthrough pain. Average pain decreased at day 7 (p < 0.001) by four points, breakthrough intensity decreased by four points (p < 0.001), and the number of breakthrough episodes decreased on average from three to one (p < 0.001). Among patients in whom the rotation was effective, there were no significant differences between pre- and postequivalent doses of opioids. In 10 switches (out of a total of 75), there were no toxicities postrotation at one week. Rotations to methadone appeared to be associated with more postrotation adverse events.

The results of this study suggest that opioid rotation can be effective for pain management and the reduction of opioid-associated toxicities in most patients. Rotations to methadone appeared to be associated with more toxicities than rotations to other medications.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Questionable protocol fidelity
• Other limitations/explanation: Throughout the study period, the total opioid doses were not maintained although there was no overall significant difference in the morphine equivalents found. The study reported results at only one week. There was no information on the length of time patients received opioids prior to the study or the severity of toxicities prior to the rotation. There was no information regarding any potential adjuvant medication use.

In patients with severe cancer-related pain, opioid rotations may be beneficial for improving pain management and addressing opioid-related toxicities. However, the duration of this effect is not clear. These results suggest that switching to methadone might not be the best choice for reducing toxicities.

To assess the safety and efficacy of methylphenidate for cancer-related fatigue. Secondary outcomes included depression, cognition, and adverse effects.

TYPE OF STUDY: Meta-analysis and systematic review

DATABASES USED: PubMed. EMBASE, PsycINFO, Cochrane Collaboration

KEYWORDS: Methylphenidate, dimethylphenidate, Ritalin, cancer, fatigue, asthenia, tiredness, and randomized controlled trial

INCLUSION CRITERIA:  Randomized controlled trials, adults older than 18 years, the trial examined efficacy of methylphenidate on fatigue, and results were sufficient to calculate effect sizes

EXCLUSION CRITERIA: None specified

TOTAL REFERENCES RETRIEVED: N = 374

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: The Jadad scale was used for quality assessment.

• N (studies) = 5
• SAMPLE RANGE ACROSS STUDIES: 10–62
• TOTAL PATIENTS INCLUDED IN REVIEW: 198
• KEY SAMPLE CHARACTERISTICS: Three studies included mixed tumor types, one was in prostate, and one was in patients with primary brain tumor.

PHASE OF CARE: Multiple phases of care

Meta-analysis was done with studies grouped according to the measure of fatigue that was used. In studies using the FACT-F (three studies), results showed a favorable effect of methylphenidate with a mean difference of -3.13 and a signficant overall effect (p -0.01). In studies using the BFI, results showed a favorable effect with mean difference of -0.69, but the Z test of overall effect was not significant. Methylphenidate had no effect on depression (two studies) or cognitive impairment (two studies). Studies varied widely in terms of the duration of treatment. Treatment for greater than four weeks was superior compared to placebo. However, treatment for less than four weeks did not show a significant effect compared to placebo. Rates of adverse effects between those getting methylphenidate and those getting a placebo were not significantly different. Those receiving methylphenidate had significantly more vertigo, anxiety, and nausea.

Results suggest that treatment with methylphenidate for at least four weeks is effective in reducing cancer-related fatigue and is not associated with a high rate of adverse effects. Treatment with methylphenidate did not improve depression or cognitive impairment. Use of different methods of measurement of fatigue showed different results.

Few studies were included, and some of these had very small sample sizes. Included studies did not provide sufficient information on relevant concomitant conditions of patients, such as sleep disorders and anxiety. Dosages and dosage increase approaches with methylphenidate varied.

Findings suggest that treatment with methylphenidate for at least four weeks can be helpful in managing cancer-related fatigue. However, the most appropriate dosages are not clear. Patients can experience side effects, and if methylphenidate is used, nurses need to monitor patients for side effects. Further large studies are needed to strengthen evidence related to effects and side effects of methylphenidate.

To determine the incidence of early onset hemorrhagic cystitis (EOHC) and identify the effectiveness of preventive measures upon EOHC

This retrospective study evaluated the effects of hyperhydration, diuresis alkalization, mesna, fluoroquinolone antibiotic prophylaxis, urethral catheterization, and CBI on 158 patients in two centers undergoing BMT regime upon EOHC. EOHC was defined as HC occurring within the 21 days after transplantation.

• N = 158  
• MEAN AGE = 41.9 years
• MALES: 59%, FEMALES: 41%
• KEY DISEASE CHARACTERISTICS: Patients receiving conditioning BMT regimes for either autologous (n = 5) or allogeneic (n = 153) BMT for hematologic malignancies  
• OTHER KEY SAMPLE CHARACTERISTICS: 40% of patients had AML.

• SITE: Multi-site    
• SETTING TYPE: Inpatient    
• LOCATION: Italy

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

• Retrospective study of patients receiving BMT regimes at two Italian centers

Groups were compared using the Mann-Whitney U test (for continuous variables) and Yates’ correction (for categorical variables). Logistic regression was used to identify factors contributing to the development of EOHC, including gender, age, smoking habits, type of transplantation, stem-cell donor, Cytoxan dose, urethral catheterization, and CBI. A multivariate regression model using a backward stepwise selection algorithm was employed.

Thirty-one patients (all allogeneic transplantations) developed EOHC. Female gender (p = 0.24) and the dose of cytoxan (p = 0.016) were identified as independent risk factors for EOHC. The daily dose of mesna was the only significant measure (p = 0.01) identified between those who developed EOHC (median = 4.463) and those who did not (3.701).

Univariate analysis does not support the current standard, prophylactic catheterization and CBI, for prevention of EOHC. The best practice includes hyperhydration association with diuresis alkalization and mesna infusions.

• Unintended interventions or applicable interventions that would influence results were not described.
• This was a retrospective study.

Nurses caring for patients at risk of HC may need to reassess current standards for prophylactic treatment of HC.

• FINAL NUMBER STUDIES INCLUDED = 13 
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,003
• SAMPLE RANGE ACROSS STUDIES = 16–230 patients
• KEY SAMPLE CHARACTERISTICS: Various tumor types, patients in active treatment undergoing chemotherapy or radiation therapy

PHASE OF CARE: Active antitumor treatment
 
APPLICATIONS: Palliative care

Interventions considered to be BT were healing touch, Reiki, and therapeutic touch. The effect on pain was examined in seven studies. There were some mixed findings, but most showed a reduction in pain over short time periods. Fatigue was assessed in five studies. These demonstrated fatigue reduction post-treatment, but data were conflicting over a longer period of four to eight weeks. Anxiety and depression were examined in seven studies. All but one found a significant reduction in mood disorders, but a study comparing Reiki, sham Reiki, and usual care found no difference between the sham and actual Reiki groups. Most studies were of descriptive or quasi-experimental design; potential confounding variables were not examined, and placebo effects could not be ruled out.

Studies using biofield therapies for relief of pain, anxiety, fatigue, and depression generally showed benefit; however, the evidence is not strong due to the limitations of the studies included.

Low-quality design studies and the short duration of study follow-up

BT therapies have not demonstrated effectiveness in well-designed clinical studies; however, though it is weak, evidence suggests potential benefit. There were no adverse effects of these interventions reported. Biofield therapies are not expensive and are low-risk, so they can be considered in the management of cancer-related symptoms. Well-designed clinical trials are needed to establish efficacy.

To describe the management of moderate to severe dyspnea in patients receiving palliative care

A retrospective study was conducted using the records of patients who were consulted by a palliative care service over a five-year period. Information about medications prescribed was collected for patients who self-reported moderate to severe dyspnea at their initial evaluations by the palliative care service. Follow-up assessments of dyspnea were conducted by the palliative care service within 24 hours of the initial assessment. Data extraction was completed by a physician.

• N = 115  
• MEAN AGE = 64 years (SD = 17 years)
• MALES: 51% (n = 59), FEMALES: 49% (n = 56)
• KEY DISEASE CHARACTERISTICS: Primary diagnoses were cancer (64%, n = 59), heart failure (8%, n = 9), and chronic obstructive pulmonary disease (5%, n = 6). 
• OTHER KEY SAMPLE CHARACTERISTICS: Half of the sample was Caucasian (54%, n = 62). Pneumonia was diagnosed in 34% of patients (n = 39), and 30% of patients (n = 35) had a pleural or pericardial effusion. 

• SITE: Single site  
• SETTING TYPE: Inpatient  
• LOCATION: Urban medical center

• APPLICATIONS: Palliative care

Retrospective chart review of patients with moderate or severe dyspnea

• Charleston Comorbidity Index (CCI) to assess the severity of illness through the classification of comorbidities to predict short- and long-term mortality
• Dosages of opioids were converted into milligrams of oral morphine per day by equianalgesic dosing.
• Plonk’s equation was used to convert methadone to morphine. 
• Dyspnea, pain, and anxiety were measured using a four-point categorical scale based on patient self-reports.
• Data from the chart review included the frequency and dose of opioids and benzodiazepines, age, sex, race, comorbidities, the presence of pneumonia, and pleural or pericardial effusion. 

Most patients reported an improvement in dyspnea within of 24 hours after palliative care service consultation. Most patients with dyspnea received opioids but only the combination of benzodiazepines and opioids was independently associated to improve dyspnea.

• Baseline sample/group differences of import
• Risk of bias (no control group) 
• Risk of bias (no random assignment) 
• Risk of bias (no appropriate attentional control condition)  
• Other limitations/explanation: The results were from a retrospective chart review. Conclusions cannot be drawn about the effectiveness of treatment or the causal relationships between medication and improvements in in dyspnea symptoms due to the study’s design. The study acknowledges potential confounding factors including patient factors, procedures, and psychological care that may impact the study’s findings. The results are reflective of the practices of one institution, which may limit generalizability. The population studied may not be generalizable to the broader palliative care population.

Because dyspnea is a common symptom in patients receiving palliative care, the authors conducted a study that reviewed the records of patients with moderate or severe dyspnea. The study found that opioids given with benzodiazepines were associated with improvements in dyspnea. Additional research to determine whether the use of benzodiazepines alone or in combination with opioids is more effective is necessary to to lead to improvements in dyspnea treatments.

To evaluate the effectiveness of preoperative dexamethasone in reducing postoperative nausea, vomiting, and pain after mastectomy

Patients were randomized to receive either IV dexamethasone 8 mg or placebo 60 minutes prior to skin incision. All patients had the same standardized general anesthesia. The same surgical team performed each surgery. Pain was assessed on entry to the recovery room and at 6, 12, and 24 hours postoperatively. Analgesia was ketorolac 30 mg every 8 hours and IV tramadol infusion 50 mg as backup medication. Patients were followed for up to 30 days after surgery.

• The sample was composed of 70 patients.
• In the placebo group, mean patient age was 49.89 years (SD = 10.58 years). In the dexamethasone group, mean patient age was 50.11 years (SD = 12.37 years).
• All patients were female.
• All patients had breast cancer. In each group, more than 90% underwent radical mastectomy with axillary node dissection.

• Single site
• Inpatient
• Guadalajara, Jalisco, Mexico

Double-blinded placebo-controlled randomized trial

• Visual analog scale, to assess pain
• Four-point ordinal scale (0 = no vomiting, 3 = vomiting), to assess postoperative nausea and vomiting

Compared to patients in the placebo group, those receiving dexamethasone had significantly lower pain scale scores immediately after surgery (p = 0.004), at 6 hours (p < 0.0005), and at 12 hours (p = 0.04). Pain score differences between groups were approximately 1 point at these times. Authors noted no differences between groups at 24 hours after surgery. More patients in the placebo group than in the dexamethasone group required analgesics (p = 0.008), and the mean dose of IV tramadol was lower for those who received dexamethasone (p = 0.03). Incidence of nausea and vomiting was lower with dexamethasone; more patients in the placebo group required antiemetics (p = 0.01)

Compared to preoperative administration of placebo, preoperative administration of dexamethasone was associated with less short-term postoperative pain, nausea, and vomiting.

• The study had a small sample size, with fewer than 100 participants.
• Patients with a history of motion sickness and other risk factors for nausea and vomiting were excluded from the study, so patients included were those at lower risk for these problems.
• Authors did not report actual intake of opioid or analgesic.

Findings suggest that preoperative dexamethasone administration can reduce short-term postoperative pain, nausea, and vomiting. In this study patients received specific anesthesia regimens. Findings may not be the same with different anesthetics. Further study in this area should identify optimal management of postoperative symptoms. The administration of a single corticosteroid dose prior to surgery can be a relatively low-risk intervention that seems to improve the patient’s experience.