To examine the risk of uncontrolled chemotherapy-induced nausea and vomiting (CINV) among patients with lung cancer receiving multiday chemotherapy and ondansetron- or palonosetron-initiated prophylactic antiemetic regimens in a community oncology setting

The Georgia Cancer Specialists electronic medical records database was used to identify patients with lung cancer who received multiday cisplatin or carboplatin regimens with ondansetron or palonosetron on day 1 between April 1, 2006, and July 31, 2009. Uncontrolled CINV was identified. Risk for uncontrolled CINV, up to 7 days after last chemotherapy administration, was analyzed at cycle level using logistic regression.

• The study reported on 362 patients; 209 of these patients received a total of 702 cycles of palonosetron, and 153 patients received 515 cycles of ondansetron.
• The palonosetron group was significantly older than the ondansetron group (66.8 years old versus 63.9 years old [p < 0.01]).
• The palonosetron group was 54% female, and the ondansetron group was 53% female.    
• Patients were diagnosed with lung cancer, received multiday cisplatin or carboplatin regimens, and used palonosetron or ondansetron on day 1 (and did not receive aprepitant on day 1). The palonosetron group received antiemetics every other day, whereas patients in the ondansetron group received ondansetron every day except for the last day, in which they received palonosetron.
• The palonosetron group had a Charlson comorbidity index of 3.6 and the ondansetron group had a Charlson comorbidity index of 3.5.
• The palonosetron group included 25 patients with multicancer diagnoses and the ondansetron group included 27 patients with multicancer diagnoses.

This was a multi-site study based on electronic medical records data from Georgia Cancer Specialist, a community-based practice that included 30 offices and 46 medical oncologists throughout Georgia.

• Patients were in active treatment.
• This study has application to late effects and survivorship.

This was a retrospective descriptive study using data from an electronic medical records review.

The rate of uncontrolled CINV events measured from first chemotherapy agent administration of the cycle (start date) through 7 days after the last chemotherapy agent administration (end date) for

• Assessment of a CINV event using
  • ICD-9-CM codes 787, 787.01, 782.02, 787.03 (nausea/vomiting), and 265.51(dehydration).
  • CPT codes 09760, 90761, 96360, and 96361 (hydration).
• Rescue medications (NDC code for dexamethasone/Decadron, diphenhydramine/Benadryl, olanzapine/Zyprexa, promethazone/Phenergan, haloperidol/Haldol, prochlorperazine/Compazine, lorazepam/Ativan, or metoclopramide/Reglan).
• Nausea/vomiting hospitalizations.
• Oral antiemetic medications and administration of fosaprepitant and aprepitant.
• IV antiemetic therapy after last chemotherapy administration of the cycle.

Rescue antiemetic after the first day chemotherapy or IV antiemetic after the last chemotherapy administration date were considered as nonprophylactic use.

• Overall, 273 uncontrolled CINV events were found during 702 platinum cycles in the palonosetron cohort (38.9%) and 455 events were found during 515 cycles (88.4%) in the ondansetron cohort (p < 0.01).
• Palonosetron cycles had 63% lower risk for uncontrolled CINV events versus ondansetron cycles (OR = 0.37, p < 0.01).
• Subanalysis by chemotherapy agents supported overall analysis (cisplatin OR = 0.09, p < 0.01, carboplatin OR = 0.46, p < 0.01).

Among patients with lung cancer receiving multiday chemotherapy cycles, administration of palonosetron on day 1 was associated with a significantly lower risk for uncontrolled CINV events versus ondansetron-initiated chemotherapy cycles.

• No appropriate control group was included.
• Retrospective EMR reviews introduce some limitations. For example, CINV events or hospitalization may have been underestimated, and at-home antiemetic use is not detectable.
• The palonosetron group was significantly older, which may have lowered CINV risk. Significantly more patients in the palonosetron group received moderately emetogenic chemotherapy than in the ondonsetron group, which may have influenced the comparison between the two.
• Race, smoking status, and alcohol use were not assessed.

For the patients receiving multiple day, platinum based chemotherapy for the treatment of lung cancer, every-other-day palonosetron would be an option to lower the risk of the incidence of uncontrolled CINV.

To evaluate the applicability and effectiveness of existential behavioral therapy (EBT)  to informal caregivers of palliative care patients with regards to psychological distress and quality of life when compared with treatment as usual

The intervention was six group sessions totaling 22 hours. The sessions focused on introductions and mindfulness, death, bereavement and mindfulness, activating resources, finding meaning, self-care and stress management, personal values for (re-)orientation, and moving forward. Sessions were administered in small (10 participants or fewer), closed groups by a trained behavioral therapist following a study manual. Evaluations occurred at baseline, pre- and post-intervention, and at 3- and 12-month follow-up (five time points).

• N = 133  
• MEAN AGE = 54.5 years (13.2 years)
• MALES: 30.1%, FEMALES: 69.9%
• KEY DISEASE CHARACTERISTICS: Primarily (92.7%) various cancer diagnoses and neurological diseases; six months or less to live; currently in an inpatient palliative care unit
• OTHER KEY SAMPLE CHARACTERISTICS: German speaking; 61.7% identified as partners, 26.3% as parents, 4% as children, and 12% as other

• SITE: Multi-site    
• SETTING TYPE: Inpatient  
• LOCATION: Munich, Germany

• PHASE OF CARE: End-of-life care
• APPLICATIONS: Palliative care 

• RCT

• Brief Symptom Inventory (BSI) subscales—somatization, anxiety, and depression
• Quality of life
  • Satisfaction With Life Scale (SWLS)—cognitive aspects
  • World Health Organization Quality of Life (WHOQOL)-BREF
  • Numeric rating scale for quality of life—QOL-NRS (single-item, scale of 1–10)
• Positive and Negative Affect Scale (PANAS)

EBT showed medium effects at the pre-/immediate post-test evaluation with improvement in anxiety (p 0.006) and on all measures of quality of life (p 0.009, 0.007, < 0.001). At the three-month evaluation, EBT showed no significant effects, with only small effect sizes on one-third of the quality-of-life measure SWLS (p 0.04). However, at the 12-month evaluation, EBT demonstrated medium effects on depression (p 0.04) and QOL-NRS (p 0.002). Interestingly, similar patterns resulted when examining secondary outcomes of affect, with significantly less negative affect demonstrated at post-test (p 0.003), which then was not noted at the three-month evaluation, and at 12 months, significantly less negative affect was measured again (p 0.003). Positive affect, although never significant, always was trending more positive than when compared with controls. High level of satisfaction existed with the group, the therapist, information, mindfulness, and values.

EBT shows promise as an intervention to improve psychological distress and quality of life for carers of patients with cancer at end of life. The effect is greatest immediately following the intervention. Additional work is required with attentional control groups and outpatient patient populations to further support the benefits of this intervention.

• Risk of bias (no appropriate attentional control condition)  
• Risk of bias (sample characteristics)
• Intervention expensive, impractical, or training needs
• Other limitations/explanation: Heterogeneous sample—variety of care types, partners versus relatives and carers of living and dead patients were included in the same groups, meaning that for some, they already were in the grieving process at the start of the intervention. When compared to treatment as usual, which is no intervention, whether EBT or just being part of a group, or having attention of the therapist accounted for the improved outcomes is unclear. Intervention included specially trained behavioral therapist, not nurses.

Interventions such as EBT that target informal carers of patients with cancer have the potential to relieve distress and improve quality of life for the carer and the patient.

RESOURCE TYPE: Expert opinion

PHASE OF CARE: Active antitumor treatment

Review article

Literature review of common checkpoint inhibitor adverse and serious adverse events. No evidence quality review was provided.

Research is needed on the management of checkpoint inhibitor therapy toxicities.

To evaluate the effects of a specialized breathlessness intervention service compared to usual care

The breathlessness intervention service (BIS) was a multidisciplinary complex intervention including nonpharmacologic and pharmacologic interventions to support patients with advanced disease and dyspnea. The BIS used first-stage interventions such as positioning to reduce the work of breathing, education, individualized exercise plans, relaxation techniques, sleep hygiene, cognitive behavioral therapy approaches, and other supports. Second-stage interventions applied concurrently included opioids, antidepressants, anxiolytics, etc. Patients referred to this service were randomly assigned to the intervention or to a wait-list control group. Study measures were obtained at baseline and after the intervention. Interviews were done before randomization, at two weeks, and at five weeks. The interviews were recorded and transcribed verbatim for analysis. A final qualitative analysis was done from 20 intervention transcripts that were purposefully sampled to obtain a diverse group from those who improved and did not improve.

• N = 54 (47 completed five-week evaluations, 39 respondents)
• MEAN AGE = 69 years (SD = 11.5 years)
• MALES: 59%, FEMALES: 41%
• KEY DISEASE CHARACTERISTICS: Lung cancer was most prevalent

• SITE: Single site  
• SETTING TYPE: Not specified    
• LOCATION: United Kingdom

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

Randomized, controlled trial

• Distress scores caused by breathlessness
• Hospital Anxiety and Depression Scale (HADS)
• Chronic Respiratory Questionnaire (CRQ)
• Numeric Rating Scale (NRS) for distress
• EuroQol Five Dimensions Questionnaire (EQ 5-D) for generic health status

Patients in the intervention group had greater reductions in breathlessness (1.68 versus 0.23 points, p = 0.049). There were no other significant differences in outcomes for patients or caregivers between study groups. Interventions identified as helpful were providing and teaching the use of a handheld fan, encouraging exercise, coaching in breathing techniques and positioning, medication changes, and referrals to other services. Total costs were lower for the intervention group, and a cost effectiveness analysis showed a 66.4% likelihood that the intervention would result in lower cost and better outcomes in terms of reduced distress from breathlessness. Scores for mastery of symptom management did not change significantly.

This complex psychoeducational and pharmacologic intervention was associated with reduced distress from breathlessness. No effects on patient or caregiver distress, anxiety, or depression were found.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Other limitations/explanation: With this complex, multicomponent intervention, it was not possible to determine which aspects were most effective in achieving improved outcomes.

Individual interventions such as opioid use have been shown to reduce dyspnea, so it was not possible to determine the relative value and utility of the combined interventions examined here. These study findings suggested that multicomponent, complex interventions to improve symptoms of breathlessness can be cost effective and improve outcomes.

To evaluate the clinical and economic impact of delayed chemotherapy-induced nausea and vomiting (CINV) on patients who received initial and maintenance therapy with the 5-hydroxytryptamine 3 (5HT3) receptor antagonist palonosetron compared to older agents

There was no intervention in this retrospective study; however, the procedure was outlined. Using the OptumInsight^® database, researchers evaluated the impact of 5HT3 on chemotherapy-naïve patients. This database provided information on all pharmacy and medical claims for each subject, and records were accessed six months prior to the initial chemotherapy treatment and six months after. Patients were not evaluated if the type of antiemetic changed or if chemotherapy was changed. ICD9 codes and pharmacy charges were monitored for primary or secondary diagnoses of nausea, vomiting, and dehydration. Economic outcomes also were evaluated and calculated.

• N = 26,974
• AVERAGE AGE = 55.7 years
• MALES: 30.9%, FEMALES: 69.1%
• KEY DISEASE CHARACTERISTICS: Patients who were chemotherapy-naïve; not receiving multiday chemotherapy; 53% breast; 20% lung; remainder split between ovarian, colon, and other cancers
• OTHER KEY SAMPLE CHARACTERISTICS: 72% of patients had a diagnosis for a single site.

• SITE: Not stated
• SETTING TYPE: Not specified  
•  LOCATION: OptumInsight database

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

Retrospective database analysis

No instruments were used, but information extracted from the database included patient and treatment characteristics, nausea, vomiting, Charlson Comorbidity Index scores, antiemetic therapy, and specific 5HT3 use.

Preindex comorbidity scores were lowest in the palonosetron group and highest in the dolasetron group. The overall rate for delayed CINV at cycle 1 was 15.6% for all groups. When compared to palonosetron, patients who received ondansetron (p < 0.002), granisetron (p < 0.001), and dolasetron (p = 0.002) had higher rates of CINV in the second and subsequent cycles of chemotherapy. Dexamethasone was consistently used in the first cycle for all treatment groups. Aprepitant was used most often in the palonosetron group (10.7%) compared to ondansetron (3.6%), granisetron (2.3%), and dolasetron (2.5%).

5HT3 agents were effective in preventing CINV. There were differences in 5HT3 efficacy and cost. Delayed CINV rates increased with subsequent cycles of older 5HT3 agents. Palonosetron showed improvement over time. Similar trends were seen with healthcare resource use.

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Risk of bias(sample characteristics)
• Key sample group differences that could influence results
• Measurement/methods not well described 
• Other limitations/explanation: Comorbidities were lowest in the palonosetron group. The palonosetron group received aprepitant more often than the other groups. This may have influenced the outcome measures. This was a claims analysis, and cases of delayed CINV may not have been captured, especially when patients were given a supply of antiemetics to use at home. This study only included patients who were commercially insured. It did not capture any complementary methods that may have been used (i.e., acupressure, nutraceutical).

This study demonstrated cost effectiveness. Medical costs constituted the largest costs. Costs were higher if a patient experienced CINV. Nurses need to use guidelines and risk factors when starting patients on chemotherapy. Using a 5HT3 agent based on the emetogenic potential of chemotherapy is important.

To investigate the safety and efficacy of intraperitoneal bupivacaine and dexmedetomidine in patients undergoing laparascopic colorectal surgery for postoperative pain management

Patients were randomized to one of three groups: (a) control (intraperitoneal injection of saline), (b) bupivacaine only (125 mg, 0.25%) injection, and (c) combined dexmedetomidine and bupivacaine (bupivacaine 0.25% and 1 mcg/kg dexmedetomidine). After hemostasis was achieved in surgery, intraperitoneal instillation of study drugs was sprayed uniformly into the periotoneal cavity guided by camera. Pain was assessed at baseline and at 2, 3, 6, 8, 12, and 24 hours postoperatively. IV tramadol (100 mg) was given when pain was at least 3 or upon patient request.

• N = 45   
• MEAN AGE = 50 years 
• MALES: 53.3%, FEMALES: 45.6%
• CURRENT TREATMENT: Other
• KEY DISEASE CHARACTERISTICS: All had colorectal cancer and were undergoing laparascopic surgical procedures. Most were undergoing hemicolectomy. Others had anterior resections.
• OTHER KEY SAMPLE CHARACTERISTICS: No differences existed between groups in duration of surgery.

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: Egypt

• PHASE OF CARE: Active antitumor treatment

• Double-blind, placebo-controlled, three-group, randomized trial

• Visual analog scale (VAS) for pain severity
• Observer's Assessment of Alertness/Sedation Scale (OAA/S)

The group that received bupivacaine and dexmedetomidine had significantly lower pain at 2, 4, and 24 hours compared to the other study groups (p < 0.03) and needed rescue analgesic much later (p = 0.0002). No difference in time to analgesia existed between study groups 1 and 2. Average overall postoperative tramadol consumption was lower in the group receiving the combined intraperitoneal analgesia (p = 0.001).

Intraperitoneal administration of bupivacaine and dexmedetomidine improved the effectiveness and duration of postoperative analgesia compared to bupivacaine alone or placebo.

• Small sample (< 100)

Findings showed that loco-regional analgesic administration after laparoscopic colorectal surgery was effective for postoperative analgesia, and the addition of dexmedetomidine to bupivacaine improved efficacy and duration of analgesic effect.

To investigate the safety and efficacy of three doses of intrathecal morphine in patients receiving major abdominal surgery

Patients were randomly assigned to receive 0.2 mg, 0.5 mg, or 1 mg of morphine injected into the L3-4 space prior to anesthesia. All patients received the same type of anesthesia and reversal. Vital signs and Visual Analog Scales for pain were assessed at six, 12, 18, 24, 36, 48, and 72 hours postoperatively. At patient request, or for a pain score greater than or equal to 3, rescue analgesia of 100 mg IV tramadol was given.

• N = 90  
• MEAN AGE = 50.45 years (range = 35–64 years)
• MALES: Not provided  
• FEMALES: Not provided
• KEY DISEASE CHARACTERISTICS: Patients had surgeries including pelvic excentration, hemicolectomy, sigmoidectomy, cystectomy, and hysterectomy. The majority of procedures were American Society of Anesthesiologists class 2.

• SITE: Single site  
• SETTING TYPE: Outpatient    
• LOCATION: Egypt

• PHASE OF CARE: Active antitumor treatment

Double-blinded, randomized trial

• Time till first analgesic request
• Total analgesic consumption
• Observers Assessment of Alertness/Sedation (OAA/S)
• Postoperative adverse effects
• Visual Analog Scale (VAS)

The mean time in hours till the first analgesic request was longer in those receiving 0.5 mg (22.13, p < 0.001) and 1 mg (30.83 , p < 0.001) of morphine. Mean total tramadol consumption also was lower in these groups (p < 0.001) with the lowest consumption in those receiving 1 mg (p < 0.04). For the first 18 hours postoperatively, those receiving higher doses of intrathecal morphine had lower pain scores (p < 0.02) than those receiving 0.2 mg. At 24 hours and beyond, there were no significant differences in pain scores among groups. More patients in the higher dose groups developed pruritus (p = 0.01). There were no other significant differences in overall adverse effects between groups. One older patient in the 1 mg dose group developed respiratory depression.

Doses of 0.5 mg and 1 mg intrathecal morphine preoperatively resulted in longer postoperative pain control and less analgesic consumption with nonsignificant differences in adverse effects compared to a dose of 0.2 mg.

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

The provision of high-dose intrathecal morphine preoperatively resulted in improved postoperative pain control among patients receiving major abdominal surgeries for cancer. Higher doses were associated with better pain outcomes for the first 24–48 hours after surgery. The administration of high-dose intrathecal morphine necessitated careful patient selection and strict postoperative monitoring.

To evaluate whether a topical menthol product has clinical benefit for pain of peripheral neuropathy

Patients were given a 1% menthol in aqueous cream and were instructed how to apply it to the affected area and corresponding dermatome region of the spine twice daily. Patients were followed for four to six weeks.

• N = 40  
• MEAN AGE = 61 years
• AGE RANGE = 20–89 years
• MALES: 37%, FEMALES: 63%
• KEY DISEASE CHARACTERISTICS: Patients had chronic neuropathic pain: 80% had chemotherapy-induced peripheral neuropathy diagnosed by a physician, and 20% had scar pain related to treatment for breast cancer. Breast and colon cancers were the most common. 
• OTHER KEY SAMPLE CHARACTERISTICS: Median of 11 months since chemotherapy treatment

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: United Kingdom

PHASE OF CARE: Late effects and survivorship

Open-label

• Brief Pain Inventory-Short Form (BPI-SF)
• Hospital Anxiety and Depression Scale (HADS)
• Leeds Assessment of Neuropathic Symptoms and Signs (LANSS)
• Walking ability: GAITRite mat to measure velocity and cadence
• Hand dexterity
• Quantitative sensory testing (QST)

Eighty-two percent showed an improvement in pain scores (p < 0.001). Significant improvements were observed in some aspects of quantitative sensory testing for mechanical detection threshold, cool stimulus, and warm stimulus. Both walking velocity and cadence improved. No significant changes in hand dexterity or LANSS scores were reported.

The findings suggest that the topical application of menthol can improve symptoms of chronic chemotherapy-induced peripheral neuropathy.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Subject withdrawals ≥ 10%

This study is limited by its small sample size and study design, but shows promising proof of concept results related to molecular receptors in sensory nerves that appear to respond to topical menthol. Very few interventions have been shown to prevent or effectively treat chemotherapy-induced peripheral neuropathy, so further research on the use of topical menthol is warranted. Further well designed studies are needed.

To determine the effectiveness of pregabalin in conjunction with radiotherapy to treat patients with cancer-induced bone pain (CIBP)

This double-blind randomized study examined the concurrent use of pregabalin with palliative radiotherapy (versus placebo with radiotherapy) to prove the efficacy of use for treatment of CIBP. Patients were given 75 mg pregabalin or placebo twice daily for 35 days. Assessment of analgesia was done every seven days from baseline. If adequate analgesia was not achieved, trial medication was increased incrementally up to 300 mg twice daily. Radiotherapy was given in either one fraction of 8 GY or 20 Gy in five fractions.

• N = 233   
• AGE:18 years or older; more than 95% of participants were 45 years or older
• MALES: 50.9% pregabalin, 60.7% placebo; FEMALES: 49.1% pregabalin, 39.3% placebo
• CURRENT TREATMENT: Radiation 
• KEY DISEASE CHARACTERISTICS: Those with radiologically proven bone metastases who were scheduled to receive radiotherapy as pain treatment and who had pain scores equal to or greater than 4 on the 0–10 pain scale
• OTHER KEY SAMPLE CHARACTERISTICS: Participants had a life expectancy greater than two months, one or more sites of CIBP being treated with radiotherapy, the ability to provide informed consent to participate in the trial, and did not currently use gabapentin and/or pregabalin in therapeutic regimen (in other words, participation in this study would be the introduction of pregabalin in those participants, not in the placebo arm). Patients who had any change in cancer treatment therapy before entering the study (with the potential to influence pain perception) were excluded.

• SITE: Multicenter
• SETTING TYPE: Outpatient
• LOCATION: Five cancer centers in the UK

• PHASE OF CARE: End-of-life care
• APPLICATIONS: Palliative care 

• Multicenter, double-blinded randomized trial

• 0-10 Numeric Rating Scale
• Brief Pain Inventory (BPI) for worst pain and pain interference
• Hospital Anxiety and Depression Scale (HADS)

No statistically significant differences in average pain, pain intereference, or quality of life were discovered. However, differences in mood and breakthrough pain duration, which was lesser in the pregabalin arm (p = 0.037), were present.

These findings do not support use of pregabalin in patients with CIBP receiving palliative radiotherapy.

• Optimal dose of pregabalin was not determined prior to the study.
• No subgroup analysis based on fractionation/schedule of radiotherapy
• No information regarding any use of bone-modifying agents

Nurses providing care to patients in the outpatient setting are in prime position to conduct further research to determine the efficacy of adjunct medications and/or other treatment modalities used for treatment of CIBP and chronic cancer pain in general. Nurses may serve as principal investigators or coinvestigators in further research to determine the most effective interventions. Nurses may also serve to make recommendations for Putting Evidence into Practice (PEP) in outpatient cancer treatment settings, and in doing so serve as patient advocates. Findings do not support the use of pregabalin for metastatic bone pain in patients with cancer.

To compare the efficacy and tolerability of fentanyl-pectin spray (FPNS) with that of immediate-release morphine sulfate (IRMS) in the treatment of breakthrough cancer pain (BTCP)

Patients in the study were experiencing 1–4 episodes of BTCP per day while taking at least 60 mg/day of oral morphine or equivalent for BTCP. Patients completing the titration phase continued to the double-blind, double-dummy phase: 10 episodes of BTCP were randomly treated with FPNS and oral capsule placebo (5 episodes) or IRMS and nasal spray placebo (5 episodes). The primary end point was pain intensity (PI) difference from baseline at 15 minutes. Secondary end points were onset PI decrease (≥ 1 point) and time to clinically meaningful pain relief. Safety and tolerability were evaluated by means of adverse events (AEs) and nasal assessments. By-patient and by-episode analysis were completed. Duration of follow-up was a maximum of 14 days in the open-label period.

• The sample was composed of 110 patients.   
• Mean patient age at baseline was 55.9 years (SD = 12.3 years). Of all patients, 65.1% were 60 years old or younger.
• Of all patients, 53.8% were male and 46.2% were female.
• All patients received fixed-schedule opioid regimens consisting of a total dose equal to or greater than 60 mg/day oral morphine for BTCP. All patients had 1-4 episodes per day of BTCP.
• Exclusion criteria barred participation of patients
  • With uncontrolled or rapidly escalating background pain.
  • Who were medically unstable.
  • Who had breakthrough pain unrelated to cancer.
  • With a past inability to tolerate fentanyl or other opioids.
  • Who anticipated receiving therapy with any pain-affecting treatment (i.e., radiotherapy, chemotherapy) during the study or who had received treatment with another investigational drug within 30 days.
  • With any disorder or using any medication likely to adversely affect normal functioning of the nasal mucosa.

• Multicenter (35 oncology centers)
• Europe and India
   

• Phase of care: active treatment
• Clinical application: palliative care

Randomized, controlled, double-blind, double-dummy, multiple crossover trial

• 11-point numeric scale (0 = no pain, 10 = worst possible pain), to measure pain intensity.
• Nasal assessments performed by the study physician.
• Four-point scale (0 = absent, 3 = severe) of subjective nasal assessment by the patient, who completed a 10-item questionnaire before the first use of the study drug, one hour after each dose of the study medication, and at the final study visit. Items rated included stuffy/blocked nose, runny nose, itching/sneezing, crusting/dryness, burning/discomfort, nosebleed, cough, postnasal drip, sore throat, and taste disturbance.
   

• Analysis of pain intensity difference pre- and post-treatment showed that FPNS provided a greater reduction in pain intensity than did IRMS, with mean ± SE 3.02 ± 0.21 for FPNS doses and 2.69 ± 0.18 for IRMS (p < 0.05). Statistical superiority of FPNS compared with IRMS, on patient-averaged PID scores, continued at each point 15–60 minutes (p < 0.05).
• After treatment, from 10 minutes onward, mean PI scores were lower for FPNS-treated episodes than for IRMS-treated episodes.
• More treatment-emergent AEs occurred after FPNS than after IRMS treatment. A higher percentage of treatment-emergent AEs occurred after 400 mcg and 800 mcg doses of FPNS. Treatment-emergent AEs were mainly mild to moderate in severity and included vomiting, somnolence, dehydration, and nausea. Of all patients, 4.7% of patients withdrew from titration due to AEs.
   

The pain intensity difference associated with FPNS was greater than that associated with IRMS. The difference between the two measures of pain intensity was statistically significant (p < 0.05).

• The study was of short duration, only 14 days. This period is not long enough to evaluate potential long-term effects on the nasal mucosa.
• The study design did not include titration to an effective dose of IRMS.

For patients receiving around-the-clock opioid treatment for chronic cancer-related breakthrough pain, FPNS appears to be effective, safe, and well tolerated. The early reduction of pain that FPNS provided either matched or exceeded that provided by IRMS. Compared to IRMS, FPNS provided more complete pain relief. The effects of long-term use of FPNS have not been evaluated; nurses must be aware that long-term effects of FPNS on the nasal mucosa are unknown.