The purpose of the study was to study the effect of administration of primary prophylactic (PPG) colony-stimulating factory and duration of administration on the occurrence of chemotherapy-induced neutropenia hospitalization in older adult patients with breast cancer.

The study sample included women older than age 66 years. Women with stage 0 were excluded because stage 0 does not require chemotherapy, and women with stage 4 were excluded because stage 4 palliative therapy is very different from standard first-course administration.

The SEER data from 16 registries (1994–2002) was used. The outcome of interest was neutropenia hospitalizations defined as ICD9 code 288.0X in the first, third or sixth months after the first course of chemotherapy.  Administration of G-CSF had to be initiated within five days after the first course of chemotherapy as primary prophylaxis. G-CSF was defined according to procedures codes.

• The total sample was 10,441 patients aged 66 years and older.
• All participants were female
• All had stage l, ll, or lll breast cancer
• Patients had to be receiving chemotherapy with in six months of diagnosis.
• Neutropenia hospitalization had to occur within the first three or six months.
• Exclusion criteria: Chemotherapy initiation after six months.
   

Inpatient

Observational study

• End result Medicare data from 1994–2003
• Outcomes and treatment defined by ICD9 diagnosis and procedure codes
   

Administration of PPG-CSF during the first course of chemotherapy reduced neutropenia hospitalizations by 16% with in first three months and 17% within the first six months of chemotherapy. Hospitalization rates within the first three months of chemotherapy initiation were three times higher in women receiving less than five days of PPG-CSF compared to women receiving PPG-CSF for five or more days. Hospitalization rates within the first one and six months were also lower with longer PPG-CSF.

PPG-CSF use is associated with reductions in patient healthcare utilization.

• No controls.
• The study does not focus on incidence of neutropenia and, rather, worked on severity
• Many mild cases of neutropenia go unreported as ANC less than 2,000.
• Neutropenia hospitalization was taken as a dependant variable for the study and patients with mild neutropenia would not be taken as a part of the study,
• Retrospective data analysis only
   

PPG-CSF received during the first three months, particularly after five days of initiation of the therapy, and to be taken for at least five days, would reduce the risk of neutropenia hospitalization among older adult patients with breast cancer.

To determine the effect of repeated intravenous injection of a monoclonal antibody, directed at the inflammatory cytokine tumor necrosis factor (TNF), on the mood of patients diagnosed with treatment-resistant depression (TRD); to note the effects of the intervention on the levels of inflammatory cytokines and high-sensitivity C-reactive protein (hs-CRP) and concentrations of TNF

Patients were randomized to receive either placebo or infliximab infusions of 5 mg/kg at baseline and at weeks 2 and 6. Assessments of clinical and inflammatory status (hs-CRP, TNF, and its soluble receptors I and II) were conducted at baseline and at weeks 1–4, 6, 8, 10, and 12.

• The sample was composed of 60 participants; 30 were in the placebo group and 30 were in the infliximab group. 
• The age range of participants was 25–60 years.
• Of male participants, 33% were treated with infliximab and 33% were treated with placebo. Of female participants, 67% were treated with infliximab and 67% were treated with placebo.
• All participants were moderately resistant to treatment in the current episode, having depression of moderate severity as measured by the treatment resistance staging method and a self-report of symptoms of depression. Group assignment was stratified by gender and by hs-CRP level (< 2 or ≥ 2).
• Of all participants, 77% were white, 20% were black, and 97% were college-educated (that is, had a college education ranging from some college to the attainment of a graduate degree). The groups were evenly matched in terms of approximate age at the time of the diagnosis of major depression, number of episodes of major depression to date, and antidepressant trials in the current episode. Authors noted no significant differences in the two test groups.

• Single site
• Outpatient
• Emory University, Division of Digestive Diseases, Atlanta, Georgia

Transition phase after active treatment

Randomized double-blind placebo-controlled trial

• Self-report
• Hamilton Rating Scale for Depression (HRSD, which the authors referred to as HAM-D; clinical response defined as at least 50% reduction in HAM-D score) and the Clinical Global Impression-Severity (CGI-S) scale
• Measures of hs-CRP, TNF, and TNF soluble receptors I and II

There were no differences in HAM-D score changes over time between groups.  These scores declined significantly over time in both groups (p = 0.01). Subgroup analysis showed that, for patients with baseline hs-CRP concentration greater than 5 mg/L, those on infliximab had greater improvement in HAM-D scores (effect size = 0.41). Treatment response rates were not different between groups

Treatment with infliximab is not an effective intervention for treatment-resistant depression. However, as levels of hs-CRP increase, infliximab has greater effect. Antagonism of TNF is ineffective against treatment-resistant depression. More research is needed to determine inflammatory biomarkers in patients who may uniquely respond to immune-targeted therapies.

• The study had a small sample size, with fewer than 100 participants.
• The study had a risk of bias due to no control.

This study yields no results that can immediately be applied to practice. Nurse-researchers should consider constructing and implementing clinical trials aimed at exploring, developing, and understanding inflammatory biomarkers to identify immune-targeted therapeutic interventions.

The purpose of the study was to evaluate if prophylaxis with oral levofloxacin will reduce or delay the febrile neutropenic episodes in chemotherapy-induced neutropenia.

Patients enrolled were assigned randomly to receive 500 mg of levofloxacin orally once daily, or an identical-appearing placebo, starting on day 1 of chemotherapy. Prophylaxis was continued until neutropenia had resolved or fever was documented. Patients were examined daily for clinical signs of infection.

The primary end point of the study was the occurrence of fever, requiring empirical antibacterial therapy during neutropenia. Secondary end points were the type and number of documented infections, the use of parenteral antimicrobial agents during neutropenia, survival at the resolution of neutropenia, compliance, and tolerability.
 

• 80 adult patients made up the sample
• Female, 35%
• Male, 65%
• All had a diangosis of acute leukemia

Active treatment
 

Prospective, randomized, placebo-controlled, single-blinded study.

• Time to first fever requiring empiric antibiotic coverage
• In non-neutropenic patients, axillary temperature exceeded 101°F and, in neutropenic patients (absolute neutrophil count of less than 500/mm³), a single oral temperature of 101ºF or higher, or a temperature of 100°F or higher for more than one hour, was taken as a sign of infection or septicemia.
• Type and number of documented infections
• Survival at the resolution of neutropenia
• Compliance
   

Levofloxacin prophylaxis reduced the incidence of fever (17/25 patients (68%) compared to18/23 patients (78%) in placebo group; relative risk = 0.87; absolute difference in risk = 10%, p < 0.001) and reduced the incidence of microbiological proven infection (4/25 [16%] in the levofloxacin group compared to 7/23 [30.4%] in the placebo group; relative risk = 0.52; absolute difference in risk = 14.4%; p < 0.001). However, patients in the levofloxacin group were more likely to have a fever that lasted more than seven days (23%) compared with the control group (12.5%, p not stated).

This prospective study does not make a strong case for the use of levofloxacin to prevent neutropenic fever in patients with acute leukemia..

• The sample size was small (less than 100).
• The statistical analysis was not described. It appears that the study is not adequately powered to detect differences between the treatment groups.
• Levofloxacin prophylaxis was started on day 1 of chemotherapy in this study, rather than after the chemotherapy in anticipation of the chemotherapy nadir, which is the more common practice.
• The risk of antibiotic resistance is a concern which is not evaluated in this study.
• This study was conducted in Bangladesh and the authors stated the concern that the hospital environment was not hygienic, so the data may not be applicable to the hospital setting in other countries.
• The statistical analyses do not appear adequate to use the data to make any definitive recommendations about levofloxacin prophylaxis.
   

This study suggests that levofloxacin may reduce fever and infection in patients with acute leukemia. There is a concern regarding antibiotic resistance with the use of prophylactic antibiotics.

To assess the effectiveness of a group mindfulness-based stress reduction program on fatigue severity and life quality measures in women with breast cancer

The intervention was a standard mindfulness-based stress reduction program consisting of mindfulness skills, meditation, relaxation, and yoga. The program was provided in a group setting once weekly over an eight-week period. Patients randomly were assigned to the intervention or control group, which received no intervention. Patients were excluded from the analysis if they did not want to continue to participate in the intervention or missed more than two sessions.

• N = 24  
• MEAN AGE = 43.6 years (range = 30–55 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All patients had breast cancer and were receiving chemotherapy.
• OTHER KEY SAMPLE CHARACTERISTICS: None provided

• SITE: Single site  
• SETTING TYPE: Not specified  
• LOCATION: Iran

• PHASE OF CARE: Active antitumor treatment

Randomized, controlled, trial 

• Fatigue Severity Scale (FSS)
• Global Quality of Life in Cancer Patients (GLQ-C30)
• Life Quality in Breast Cancer (QLQ-BR23)

Role, emotional function, social function, and cognitive function improved over time in both groups. Pain and fatigue declined over time in both groups (p < 0.001). There was a significant effect of group assignment over time with greater improvements in the intervention group for fatigue and pain (p < 0.001) as well as multiple areas of functioning.

Mindfulness-based stress reduction may be helpful in the management of fatigue among women receiving treatment for breast cancer.

• Small sample (< 30)
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Other limitations/explanation: No information was provided regarding adherence to sessions or drop-outs during the study.

Mindfulness-based stress reduction may be helpful for patients with cancer in the management of fatigue and some aspects of quality of life. Additional research involving the use of therapy interventions provided in groups should include appropriate group and attention control conditions because these factors can be expected to have an effect on perceived symptom severity.

To examine the effects of an integrated yoga program in reducing frequency and intensity of nausea and vomiting in chemotherapy-naïve patients with early stage breast cancer 

Patients were randomly assigned to receive either a yoga intervention or a supportive therapy intervention. Patients in the yoga group received both supervised and home practice of yoga sessions for 60 minutes daily, starting prior to chemotherapy. These patients received supervised initial training, audio and videocassettes for home use, and a supervised home visit. Patients in the control group received supportive therapy and coping preparation during hospital visits over a complete course of chemotherapy. Both interventions were initiated prior to the first chemotherapy cycle. The yoga instructor was trained in counseling and facilitated both groups. 

• The study consisted of 62 participants. The yoga intervention group had 28 patients, and the supportive therapy intervention group had 34 patients.
• Patients ranged in age from 30–70 years.
• All patients had at least a high school education.
• Patients were chemotherapy naïve with recently diagnosed, operable stage II or III breast cancer with a treatment plan that included surgery followed by adjuvant chemotherapy or both adjuvant chemotherapy and radiation therapy.
• Patients had Zubrod’s performance statuses of 0–2.
• Patients were excluded from the study if they had a medical condition that was likely to interfere with treatment; major psychiatric, neurologic, or autoimmune disorders; known metastases; a history of intestinal obstruction; or a known sensitivity to antiemetics.

Patients were recruited from a comprehensive cancer care center in India.

Patients maintained diaries to record episodes of vomiting and duration of nausea, and, at the fourth cycle, they completed the Morrow Assessment of Nausea and Emesis (MANE), State-Trait Anxiety Index (STAI), Beck Depression Inventory (BDI), Functional Living Index-Cancer (FLIC), and a symptom checklist questionnaire.

• The severity of post-chemotherapy vomiting was mild to moderate in both groups.
• The nausea severity was moderate to severe for the control group and mild to moderate for the yoga group.
• Frequency and intensity of nausea were lower in the yoga group. In addition, intensity of anticipatory nausea and vomiting was lower in the yoga group compared to the control group.
• A positive correlation was found between MANE scores and anxiety, depression, and distressful symptoms.

The yoga intervention was effective in reducing the frequency and intensity of nausea and the intensity of anticipatory nausea and vomiting in women with early stage breast cancer.

• The antiemetics for the management of delayed emesis were not based on guidelines or consensus statements.
• Participants in the control group were offered supportive therapy and coping less frequently than the yoga intervention group. In addition, the yoga group started the intervention earlier than the control group, closer to the time of surgery and radiation than chemotherapy.
• With the overlap of physical symptoms of cancer, the BDI and STAI in cancer populations have limitations.

To examine whether the post hoc analysis presented here confirms the original findings of the APF530 phase III trial, that APF530 is an alternative to palonsetron for preventing acute and delayed chemotherapy-induced nausea and vomiting (CINV) after moderately emetogenic chemotherapy (MEC) and highly emetogenic chemotherapy (HEC)

In the original study, patients were randomized 1:1:1 to receive APF530 500 mg subcutanous plus placebo IV, APR530 250 mg subcutaneous and palonosetron 0.25 mg plus placebo. The first objective was to establish noninferiority of APF530. For the second cycle, the placebos were dropped, and individuals who had been randomized to the palonsetron were randomly assigned to either 250 or 500 mg of APR530.

• N = Original study: 1,341 patients, secondary analysis: 1,299 patients (609 in the MEC group and 690 in the HEC group). Forty-two patients were dropped because they were reclassified as receiving regimens now considered less emetogenic than MEC. Of the remaining subjects, almost 50% were reclassified from MEC to HEC or HEC to MEC.  
• MEAN AGE = 60.3 years (MEC group), 53.4 years (HEC group)
• MALES: 24.8%, FEMALES: 75.2%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: The most common tumors were lung, ovarian, and breast.

• SITE: Multi-site   
• SETTING TYPE: Multiple settings    
• LOCATION: International study—United States, Europe, India

ACUTE PHASE OF CARE: Active antitumor treatment

Secondary analysis of a randomized, controlled study

Complete response (CR) was measured by no emetic episodes and no use of rescue medications during the acute and delayed phases of CINV after cycle one. Noninferiority was established if the confidence interval for the difference in CR was greater than 15%.

The results of this secondary analysis did not find significance difference between APF530 and palonsetron for acute and delayed CINV in patients receiving HEC and MEC regimens. There were no notable differences in the results of this study and the original analysis, except they found numerically higher CR rates in patients receiving MEC and lower CR rates in patients receiving HEC for all study arms.

The post hoc analysis presented here confirms the original findings of the APF530 phase III trial, that APF530 is an alternative to palonsetron for preventing acute and delayed CINV after MEC and HEC.

Post hoc analysis

The results of this study will not change the current use of slow-release granisetron (noninferior to palonsetron) for acute and delayed CINV after HEC and MEC, but confirms previous knowledge with new ASCO emetogenicity criteria.

To compare two dose levels of AFP530 and palonosetron in preventing acute and delayed chemotherapy-induced nausea and vomiting (CINV) after moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC)

Eligible patients were 18 years of age or older with a confirmed malignancy scheduled to receive single-day MEC or HEC defined by the Hesketh algorithm. Patients were stratified according to their chemotherapy emetogenicity (MEC or HEC) and randomized 1:1:1 to receive APF530 at 250 mg subcutaneously (granisetron 5 mg) plus a placebo IV; APF530 at 500 mg subcutaneously (granisetron 10 mg) plus a placebo IV; or palonosetron IV at 0.25 mg plus a placebo subcutaneously prior to chemotherapy. After cycle 1, all patients were invited to continue in the study. If they consented, they were rerandomized to maintain blinding, but only patients who received IV palonosetron in cycle 1 were actually randomized 1:1 to receive APF530 at 250 or 500 mg subcutaneously for less than or equal to three subsequent cycles. Efficacy measures were determined from patient diaries in which patients recorded emetic episodes, rescue medications, and the severity of nausea for each 24-hour period after chemotherapy.

• N = 1,396 (653 received MEC, 742 received HEC)
• MEAN AGE RANGE = 54.8–58.1 years 
• MALES: 27.2%–12.25%, FEMALES: 62.8%–87.75% (across treatment arms and emetogenicity strata)
• KEY DISEASE CHARACTERISTICS: 63.3%–69.5% patients with breast cancer receiving MEC; 25.4%–32.8% patients with lung cancer; and 25.4%–27.6% patients with breast cancer receiving HEC
• OTHER KEY SAMPLE CHARACTERISTICS: Greater than half of the patients received prior chemotherapy. Eastern Cooperative Oncology Group performance statuses were greater than or equal to 2.

• SITE: Multi-site    
• SETTING TYPE: Not specified    
• LOCATION: 103 centers in the United States, Poland, and India

• PHASE OF CARE: Active antitumor treatment

Prospective, multicenter, randomized, double-blinded, double-dummy, parallel-group, phase 3 trial

• Efficacy measures were determined from diaries in which patients recorded emetic episodes, rescue medications, and the severity of nausea for each 24-hour period after chemotherapy.

The original analysis under the Hesketh criteria for emetogenicity demonstrated that AFP530 at 250 and 500 mg subcutaneously was noninferior to palonosetron as assessed by complete response (CR) in the control of acute CINV after MEC (CR rates of 74.8% and 76.9%, respectively, versus 75% for palonosetron). The result was similar for patients receiving HEC with acute CR rates of 77.7% and 81.3% for APF530 at 250 mg and 500 mg, respectively, versus 80.7% for palonosetron. APF530 at 500 mg subcutaneously also was noninferior to palonosetron in preventing delayed CINV after MEC with a CR rate of 58.5% versus 57.2% for palonosetron. The superiority of APF530 at 250 or 500 mg subcutaneously versus palonosetron at 0.25 mg IV in preventing delayed CINV after HEC in cycle 1 was not determined. However, CR rates were similar for APF530 at 500 mg subcutaneously and palonosetron at 0.25 mg IV. In a post hoc analysis, patients receiving chemotherapy regimens whose antiemetic risk had been revised according to the updated antiemetic practice guidelines (notably cyclophosphamide plus anthracyclines [reclassified from MEC to HEC] and carboplatin-based regimens [reclassified from HEC to MEC]) were reclassified at the request of the U.S. Food and Drug Administration. The results of this reanalysis showed no notable statistic or clinical difference in response rates between APF530 and palonosetron.

A single, subcutaneous APF530 injection offered a convenient alternative to palonosetron for preventing acute and delayed CINV after MEC or HEC with similar safety profiles.

• Measurement/methods not well described
• Other limitations/explanation: Patient diaries and ratings were not clearly described. Chemotherapy was single-day only, and nausea and vomiting was measured for only a 24-hour period.

Single-dose APF530 subcutaneously was noninferior to palonosetron at 0.25 mg IV for controlling acute CINV in patients who received single-day MEC or HEC as determined by CR. This provides another option for antiemetic chemotherapy premedication. Because of changing emetic classifications, antiemetic study interpretation can be a complicated process. The findings of this study cannot be generalized to multiday chemotherapeutic regimens because multiday chemotherapeutic regimens were not included in the design of the study.

To draw a comparison between the therapeutic effects of treatment modalities (topical steroid, honey, honey plus coffee) in patients with oral mucositis

Patients were randomized to one of three groups that each received a 600 g syrup solution. The solution in the steroid group (S) contained 20, 8 mg Betamethasone solution ampoules. The solution in the honey plus coffee group (HC) contained 300 g of honey plus 20 g of instant coffee. The solution in the honey group (H) contained 300 g of honey. Every three hours for one week, patients were instructed to sip 10 ml of their solution and swallow it. Data were collected prior to the initiation of the intervention and one week later. Patients were not allowed to use any other anti-inflammatory agents during the study. Patients and providers were blinded to the groups.

• N = 75
• AVERAGE AGE = 55.2 years
• MALES: 48%, FEMALES: 52%
• KEY DISEASE CHARACTERISTICS: None presented
• OTHER KEY SAMPLE CHARACTERISTICS: Participants who presented with oral mucositis after chemotherapy during a period of three years at the hospital site; patients with oral mucositis after chemotherapy between 15 and 80 years old

• SITE: Single-site    
• SETTING TYPE: Inpatient    
• LOCATION: Baqiyatallah University Hospital, Tehran, Iran

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Pediatrics, elder care, palliative care 

Double-blinded, randomized clinical trial

• The World Health Organization (WHO) oral toxicity scale was used to grade oral mucositis.
• A physician-rated questionnaire was created and validated for this study (questions not available).

All three regimens significantly reduced oral mucositis at the end of the intervention week (p < .05).

A steroid solution, honey plus coffee solution, or honey only solution reduced the severity of oral mucositis after one week of treatment.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no appropriate attentional control condition)
• Unintended interventions or applicable interventions not described that would influence results
• Key sample group differences that could influence results
• Findings not generalizable
• Other limitations/explanation: The study did not take into account what chemotherapy regimens the participants received or the point in the treatment regimens at which mucositis developed. The study also did not report which disease characteristics the participants had prior to treatment. The study did discuss in great length how each solution was prepared. There was no control group.

Further investigation is needed on this intervention taking into account participants' diseases and chemotherapy regimens received.

To assess the long-term tolerability, acceptability, and consistency of fentanyl-pectin nasal spray (FPNS) in patients with breakthrough cancer pain

Newly enrolled patients participated in four study phases. Phase 1 was screening. Phase 2 consisted of dose titration based on the approach used in controlled trials: The lowest FPNS dose was uptitrated, one dose per episode of pain, to a maximum of 800 mcg per dose until two consecutive episodes of breakthrough cancer pain were successfully treated without causing adverse events. Phase 3 consisted of 16 weeks of open-label treatment: Patients were provided with a four-week supply of FPNS, either 100 mcg/spray or 400 mcg/spray, based on the findings in the titration phase. Patients self-administered FPNS. If FPNS was ineffective, patients could take their usual analgesia. Investigators initiated weekly calls to patients during the first four weeks. In these calls patients and investigators discussed progress, dose adjustments, and side effects. An investigator considered dose adjustment during the participant’s monthly visit. Consideration was based on information in an e-diary, which each patient submitted, and drug-related adverse events. Phase 4 was the end-of-treatment phase. Those previously enrolled in phase III CP043 (FPNS compared to placebo in the United States, Argentina, and Costa Rica) or CP044 (FPNS compared to immediate-release morphine sulphate in the European Union and India) went through phase 3 and phase 4.

• The sample was composed of 403 patients.
• Mean patient age was 53.8 years.
• Of all patients, 53.1% were male and 46.9% were female.
• Patients had to have a histologically confirmed diagnosis of cancer.  
• To be eligible, participants could have more than one type of breakthrough cancer pain or pain in multiple areas; however, only one location and cancer type were considered the target of the medication.
• Participants could not participate if they had
  • Uncontrolled or rapidly escalating background pain or were medically unstable
  • Breakthrough pain not primarily related to cancer
  • Inability to tolerate fentanyl or other opioids
  • History of alcohol or substance abuse
  • Been treated with monoamine oxidase inhibitors or with investigational drugs within the previous 30 days
  • Any disorder or medication use that would adversely affect the normal function of the nasal mucosa

• Multisite
• Outpatient
• A total of 91 centers in Argentina, Costa Rica, the Czech Republic, France, Germany, the United Kingdom, India, Italy, the Netherlands, Poland, Spain, and the United States
   

• Phases of care: multiple
• Clinical applications: late effects and survivorship, end of life, palliative care
   

Multicenter open-label study

• Episode acceptability assessment    
• Breakthrough pain questionnaire
• Electronic diary that recorded patient's overall satisfaction by means of satisfaction scales
• Survey of adverse events recorded in categories (mild, moderate, and severe)
• Objective nasal assessments
• Subjective nasal assessment
   

• Analysis for intent to treat and safety included 403 patients; 356 entered the treatment phase, and 110 completed the full 16 weeks.
• Approximately 25% of the 403 patients experienced treatment-related, treatment-emergent adverse events that were mild to moderate and typical of opioids. Twenty patients stopped treatment because of an adverse event, and nine stopped as a result of an adverse drug reaction.
• Nasal assessments revealed no significant effects.
• Of all treated episodes, 94% required no additional rescue medication. During the study, more than 90% of patients did not have to have their dose increased. Patients were satisfied with overall outcome for 90% of episodes. At 12 weeks, 97% were satisfied with the ease and convenience of FPNS.

Per patient reports, FPNS is generally easy to use and well tolerated for the treatment of breakthrough cancer pain. FPNS doses were relatively stable during this four-month study; typically, multiple dose changes were not required. Spray, as a means of delivery, is a benefit, especially to those who have difficulty taking pills. The FPNS had little effect on the nasal passages. The results of this study appear generalizable, and administration of fentanyl by means of a nasal spray appears to be acceptable in many institutions across the world. All these outcomes indicate that FPNS may be a helpful intervention for the treatment of breakthrough cancer pain.

• The study had a risk of bias due to no appropriate control group.
• Inclusion of individuals with multiple sites and multiple locations of pain and presentation of pain could have affected  outcomes: Focusing on a primary site of pain, for the purpose of a study, is difficult.
• The study was observational and did not include active comparators.
• Selection bias presents a concern, especially considering the acceptability analysis.
   

Education regarding nasal spray administration seems to play a large role in the effectiveness of a spray-delivered intervention. Further research should investigate adverse events, to ensure the well-being of patients.

To investigate constipation and the use of laxatives in patients with chronic cancer pain treated with oral morphine and transdermal fentanyl.

Patients were switched from long-acting morphine to fentanyl patches. Fentanyl doses were calculated with a conversion table based on a 100:1 dose ratio. If the calculated fentanyl dose was higher than 2.4 mg/day = 100 ug/hour (more than 270 mg/day slow-release morphine), more than one patch was used. Patients were treated with oral slow-release morphine for at least six days (morphine phase) until they reported stable pain intensity scores of 40 or less on a visual analog scale (0 = no pain, 100 = worst pain imaginable) for at least two days. Analgesic therapy then was switched from oral morphine to transdermal fentanyl (fentanyl phase). Fentanyl patches were changed regularly after three days. Fentanyl doses were increased when patients reported inadequate pain relief or had to take more than six rescue medications per day. The study was terminated after 30 days of transdermal therapy. Patients who completed the study until day 17 or longer were included in an intraindividual comparison of laxative intake using the Wilcoxon rank test.

• The study reported on a sample of 46 patients (29 males and 17 females).
• Median patient age was 57.5 years (range 31-83).
• Median patient weight was 62.5 kg, and median height was 172 cm.
• Sites of primary cancer included gastrointestinal, head and neck, genitourinary, respiratory, breast, and hematologic.

• Germany, June 1995 to January 1996
• Unclear if inpatient or outpatient; the researcher was based at the University of Cologne.

This was an open, sequential, multi-center study.

• Patient diary recording of intensity on a 0 to 10 visual analog scale three times daily, frequency of breakthrough pain and use of as-needed medications, use of laxatives, and self-assessment of frequency and consistency of defecation.
• European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QOL-C30), with 30 items that assesses nine symptoms and six dimensions of quality of life.
• Blood pressure, heart rate, respiratory rate, and skin reaction at the site of fentanyl application were documented by the treating physician on days 0, 6, 12, 18, 24, and 30.

• Forty-six patients were treated with slow-release morphine (7 were excluded in the morphine phase because stable analgesia could not be achieved), and 39 were switched to transdermal fentanyl.
• Twenty-three patients completed the study. Two patients died from basic disease, 12 were excluded for various reasons, and two did not have enough data available for evaluation.
• The frequency of bowel movements did not change significantly, but the use of laxatives was reduced in 23 and increased in 2 of 28 patients on transdermal fentanyl.
• No significant changes in vital signs were noted.
• Mild-to-moderate skin reaction was noted in five patients.
• The EORTC QOL-C30 symptom scores showed a significant decrease for constipation only.

The use of laxatives was reduced significantly with transdermal fentanyl.

• This was an open study, so prejudices from staff or patients may have biased the results.
• The site of primary tumor was situated in the gastrointestinal tract for about 25% of the patients; in those patients, constipation easily may have been caused by tumor growth.
• It may be questioned whether the conversion from morphine to fentanyl really was equianalgesic. Therefore, less constipation may have been the consequence of lower equianalgesic opioid dosage.
• Results may have been influenced by the high number of patients who dropped out of the study.
• Difference in the degree of constipation experienced by patients between the two analgesics regimens should be confirmed in a randomized, double-blind study that takes into account both constipation and use of laxatives.
• Short-acting morphine was used for breakthrough pain in both arms of the study; as a result, the patients on fentanyl also had morphine on board.
• The laxative used was not standardized; whether this influenced the results is unclear.
• The study was supported by a research grant from a pharmaceutical company.