To evaluate efficacy of palifermin versus placebo for prevention of oral mucositis (OM), as well as burden of patients with multiple myeloma (MM) who receive autologous stem cell transplant (SCT)

This randomized study compared three groups: (1) placebo, (2) palifermin on days -6, -5, -4, 0, 1, and 2 (pre-/post-SCT), and (3) palifermin on days 0, 1, and 2 (post-SCT). The palifermin dose was 60 µg/kg per day IV. Patients were assessed daily for OM from day 2 until day 32 or discharge.

• The study reported on 257 patients with MM.
• Median age was 57 years old with a range of 32–69 years.
• The placebo group sample was 58% male and 42% female; the group 2 sample was 55% male and 45% female; and the group 3 sample was 54% male and 46% female.
• All patients were receiving autologous SCT and high-dose melphalan.

This was a multisite, inpatient study conducted in the Netherlands.

• Patients were undergoing the active antitumor treatment phase of care. 
• This study has clinical applicability for elder care.

This was a randomized, placebo-controlled, parallel-group study.

• The World Health Organization (WHO) scale for OM, the Oral Mucocitis Daily Questionnaire, and the Quality of Life Utility Scale were used.
• Investigators recorded the use of opioids, non-opioids, days of severe OM, incidence of infections, time to absolute monocyte count (AMC) recovery, and adverse events.

• No statistically significant differences were found in maximum OM severity. Severe OM occurred in 37% of patients in the placebo group, 38% in the pre-/post-group (group 2), and 24% in the pre- group (group 3).
• No significant differences were observed with respect to PRO assessments or medical resource use, but more infections and fever during neutropenia were reported in group 2 versus the placebo group (51% versus 26%).
• No significant differences were found across groups in incidence of ulcerative OM or duration of OM. Those on palifermin pre-transplant had significantly lower incidence of opioid analgesic use compared to placebo (p = 0.03).

Palifermin was unable to reduce OM or OM-related patient burden in patients with MM undergoing transplant.

• A risk of bias exists because no blinding was done.
• Unintended interventions or applicable interventions that could have influenced results were not described.
• Findings are not generalizable.
• The authors indicated that the short period of intervention time or timing of giving palifermin may have had a suboptimal effect with palifermin. The authors also suggested that hyperkeratosis may have been misinterpreted for mucositis, despite observer training in assessment.

Short term of use of palifermin for auto-SCT in patients with MM undergoing transplant was not effective in reducing OM. The fact that authors suggest that hyperkeratosis may have been incorrectly interpreted as OM suggests that correct assessment can be an issue in evaluating this symptom. Findings suggest that the specific timing of use of this agent may be critical. In using palifermin, nurses need to be aware of the appropriate timing in concert with timing of antineoplastic treatment and treatment effects.

Parenteral nutrition supplemented with 0.57 g/kg glutamine-dipeptide was started on day 6 for a median of 19 days for patients in the treatment group.

• The sample consisted of 32 patients receiving allogenic stem cell transplantation.
• Median age in the treatment group was 49 years old with a range of 25–64 years. Median age in the control groupw as 48 years old with a range of 28–57 years.

The study was conducted between July 1999 and July 2002.

This was a randomized, double-blinded, placebo-controlled pilot study.

Oral assessment was conducted daily. Lesions, erythema, edema, pain, bleeding, dryness, and the production of viscous mucous were scored on a 0–3 scale and summed to produce a daily oral mucositis score (DMS).

• DMS was 8.1 (SD = 3.5) in the glutamine group versus 9.3 (SD = 3.1) in the placebo group; results were not significant.
• No difference was found in mean daily dose of morphine to alleviate mucositis-related pain.

• The sample size was small.
• Multiple other measures were used; most were not significant.

To evaluate the efficacy of a topical gel containing lorazepam, diphenhydramine, and haloperidol (ABH), in reducing chemotherapy-induced nausea and vomiting (CINV) among patients with cancer

This article reported on two pilot trials.

Patients in one physician practice were prescribed prophylactic antiemetics according to standard guidelines. They were given a prescription for six prefilled, capped tuberculin syringes of ABH gel when they received emetogenic chemotherapy. The patients were instructed to use the ABH gel when they developed significant nausea or vomiting in the days that followed chemotherapy, with the option to repeat use at six-hour intervals. Patients were instructed to place 0.5 ml of the gel on the palmar aspects of their wrists using the prefilled syringe. After applying the gel, the participants were instructed to rub their wrists together gently for one to three minutes to facilitate transdermal absorption.

In the first trial, an investigator contacted patients by telephone within one month. Patients provided verbal informed consent at this time. The investigator asked patients questions about their progress with ABH gels using a standard questionnaire, developed for the pilot. Patients were asked to rate their CINV and if they believed the gel to cause sedation, skin irritation, or muscle spasms.

In the second trial, after patients provided verbal consent, an investigator used a structured interview by telephone or in person to rate the severity of CINV on a combined scale at 30 minutes and fours hours after applying the ABH gel.

• Trial 1 consisted of 23 adult patients with solid tumor or hematology cancer diagnosis receiving chemotherapy.
• Trial 2 consisted of 10 adult patients with a cancer diagnosis.
• No control for diagnosis or chemotherapy treatment was included.

The trials were conducted at the outpatient clinic of a university in the midwestern United States.

• Trial 1 incorporated the use of a standardized questionnaire developed for the study.
• Trial 2 involved the use of a numeric rating scale, ranging from 0 (no nausea or vomiting) to 10 (worst imaginable nausea or vomiting).

• In trial 1, 74% of patients believed the gel decreased their nausea and 70% of patients experienced relief from vomiting. The majority of patients (70%) reported relief within 30 minutes of applying the gel. Some of the patients (13%) reported fatigue after using the gel. No patients reported skin irritation or muscle spasms.
• In trial 2, nausea scores significantly decreased at 30 minutes. No significant side effects were reported.

Transdermal ABH gel decreased the severity of CINV with only slight sedation reported.

• The sample size was small and heterogeneous.
• No control for disease, chemotherapy agents, cycle, or antiemetic agents was included.
• Trial 1 was retrospective, asking participants to recall symptom experience.

Use of transdermal ABH is convenient and easily taught to patients; however, availability of this combination topical agent may be a challenge in community settings because hospital pharmacies are less likely to compound products.

To evaluate the use of palonosetron compared to ondansetron for the complete control of chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic oxaliplatin or irinotecan plus a fluoropyrimidine regimen

Patient charts were reviewed for time periods before the use of palonosetron and after use of palonosetron. Prior to use of palonosetron, ondaansetron was given in combination with 12 mg oral dexamethasone 30 minutes prior to chemotherapy on day 1 of each regimen.  In the post palonosetron group, palonosetron was used instead of ondansetron.  In the setting of grade 1 or more vomiting or grade 2 nausea, aprepitant was added to the regimen. Nurses graded nausea and vomiting during chemotherapy administration.

• The study consisted of 305 participants.
• The majority of patients (73%) were more than 50 years old.
• The sample was 53% male and 47% female.
• Patients had been diagnosed with gastrointestinal cancers.
• In early-stage disease, more patients had received oxaliplatin. The highest percentage of patients in this study had metastatic colorectal cancer.

This was a single-site study conducted in both the inpatient and outpatient settings of a Midwest (Ohio) Academic medical center.

• All patients were in active treatment.
• This study has application to palliative care.

This study was a retrospective review of patients’ medical records.

• Failure of the prophylactic antiemetic was considered the primary endpoint in both groups. Failure was defined as vomiting at grade 1 or more or nausea at grade 2 or more. 
• The Common Terminology Criteria for Adverse Events, version 3, was used for grading.

With the use of palononsetron, the incidence of CINV failure was 28.4% versus 50.3% with the use of ondansetron (p < 0.001) regardless of the agent used (oxaliplatin or irinotecan).

The findings of this study support the use of palonosetron in regimens that include oxaliplatin or irinotecan plus either 5-FU or capecitabine. The study reported that the use of palononsetron resulted in a statistically significant reduction in the risk of CINV.

• A risk of bias exists because assignment was not random.
• Unintended interventions or applicable interventions that would influence results were not described.
• Measurement and methods were not well described.
• Antiemetic failure in the acute setting versus the delayed setting was not distinguished.

Although the National Comprehensive Cancer Network (NCCN) Guidelines for Antiemesis state that, for moderately emetogenic chemotherapy, a 5-HT₃ antagonist and dexamethasone should be used to prevent CINV, this study showed that, for regimens with oxaliplatin or irinotecan and either 5-FU or capecitabine, the 5-HT₃ of choice may be palononsetron. What is unknown is whether the use of palononsetron is equally as effective in reducing CINV using other moderately emetogenic chemotherapeutic regimens.

• DATABASES USED: Not stated
• KEYWORDS: Not stated
• INCLUSION CRITERIA: Not stated (based on each reviewer’s experience)
• EXCLUSION CRITERIA: Not stated

PHASE OF CARE: Active antitumor treatment

Many systematic reviews were used as references such as the Cochrane Library, but no number articles reviewed or how these were chosen were mentioned. Selection was based on each reviewer’s experience. 

• Assess and eradicate dental infection sites ahead of radiation therapy and transmit irradiated volumes to the dentist
• Use a soft toothbrush and replace it regularly
• Apply fluoride to dental splints
• Perform regular mouth rinses with nonalcoholic saline solution
• Ensure the early diagnosis and treatment of bacterial, fungal, and viral super infections (grade B).

• No clear statement of review process
• No stated inclusion or exclusion criteria
• Number of articles retrieved and reviewed for these guidelines was not provided

The categorization using the ANAES guides to determine level of evidence and grades was appropriate. However, the search methods used in these guidelines were not clearly stated and need reconfirmation because there was no way to know whether the search was comprehensive. The recommendations were grade B and expert opinions.

To evaluate the maintenance of efficacy and safety during long-term treatment with combined oxycodone/naloxone prolonged-release tablets (OXN PR) in adults with moderate-to-severe chronic pain.

474 patients received open-labeled OXN PR during 52 weeks of extension phases of two studies, having completed 12 weeks of double-blinded, randomized treatment with oxycodone prolonged-release tablets (Oxy PR) (n = 160) or OXN PR (n = 162). The starting dose was the effective analgesic dose of OXY or OXN that the patient received at the end of the double-blind phase. Dose titration was to a maximum of 80 mg per day (OXN3001S) or 120 mg per day (OXN3006S) at the discretion of the investigator. Use of laxatives and analgesic rescue therapy was recorded in patient diaries. Oxycodone immediate-release (IR) and bisacodyl were provided for the first seven days of the extension phase. Protocols for rescue medicines and laxatives were prescribed according to standard protocols of the investigational sites. There were seven mandated office visits.

• N = 474  
• AGE = 362 aded 65 and younger; 112 older than age 65
• MALES: 36.9%, FEMALES: 63.1%

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

• PHASE OF CARE: Mutliple phases of care

• Pooled analysis of two Phase III double-blind, randomized studies

• Analgesia and bowel function were assessed at each study visit using average pain over last 24 hours scale and Bowel Function Index (BFI).
• Treatment Satisfaction Questionnaire for Medication (TSQM) was assessed at end of study only.

Improvement in bowel function was seen when patients switched from Oxy PR in the double-blinded phase to OXN PR in the extension phase, resulting in a clinical reduction (greater points) in BFI score: At the start of the extension phases, mean BFI score was 44.3 (SD = 28.13) and was 29.8 (SD = 2.36) for patients who had received OXN PR in the double-blinded phase. One week later, BFI scores were similar for the two groups (26.5 [SD = 24.4] and 27.5 [SD = 25.6], respectively), as was observed throughout the following months. Fewer than 10% of patients received laxatives regularly. Mean 24-hour pain scores were low and stable throughout the extension phases. No unexpected adverse events were observed.

Pooled data demonstrated OXN PR in patients with moderate-to-severe chronic pain is an effective long-term therapy for patient opioid-induced pain. Improvement in bowel function was seen during the double-blinded studies and was continued throughout the 52 weeks of OXN PR versus Oxy PR in this pooled analysis. No new or unexpected safety issues were observed, and patient satisfaction was high and maintained throughout the 52 weeks.

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)

Prolonged-release oxycodone/naloxone (OXN PR) is a good option for patients with opioid-induced constipation.

To compare the biosimilar to reference filgrastim

Patients were randomized to receive the biosimilar or filgrastim for the duration of treatment or to alternate at each chemotherapy cycle. Chemotherapy was given every three weeks for six cycles. Patient assessments were done at baseline, on day 1 of each cycle. For cycles 2–6, complete blood counts were assessed on day 7 and daily thereafter.

• N = 218   
• MEDIAN AGE = 50 years
• AGE RANGE = 23–76 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Breast cancer 
• OTHER KEY SAMPLE CHARACTERISTICS: Patients undergoing treatment with docetaxel, doxorubicin, and cyclophosphamide (TAC) chemotherapy

• SITE: Multi-site   
• SETTING TYPE: Not specified    
• LOCATION: Eastern European countries

• PHASE OF CARE: Active antitumor treatment

• Noninferiority, double-blind, randomized, controlled trial

• Days of neutropenia—absolute neutrophil count (ANC) < 0.5 x 10⁹ to ≥ 0.5 x 10⁹  number of consecutive days
• Infections 
• Incidence of hospitalization related to febrile neutropenia (FN)

The number of consecutive days of neutropenia was 1.17 in the biosimilar group and 1.2 in the filgrastim group. No significant differences existed in the time to ANC recovery or adverse events. In those receiving the biosimilar, fever episodes were reported in 15% compared to 4.3% of those receiving filgrastim.

This study showed no clinically meaningful differences in neutropenia-related outcomes between patients receiving figrastim and a colony-stimulating factor (CSF) biosimilar.

The findings showed similar clinical results with filgrastim and this CSF biosimilar.

The study's primary aim was to evaluate the safety and efficacy of modafinil in improving cancer-related fatigue. Its secondary aim was to determine the effect of modafinil on depression, quality of life, functional status, and cognitive function.

Participants were given 100 mg of modafinil daily for weeks 1 and 2, and then 200 mg daily for weeks 3 and 4. Participants older than 80 were dose-reduced and received 50 mg of modafinil daily for weeks 1 and 2, then 100 mg daily for weeks 3 and 4. There was no control group.

Testing was completed at baseline, week 2, and at the completion of the trial. 

• The total number of participants was 27, with 19 completing the study.
• The average participant age was 60 years.
• 63% of participants were female and 37% were male.
• 37% of participants had an Eastern Cooperative Oncology Group (ECOG) score of 1, 44% had a score of 2, and 19% had a score of 3. 

This was a prospective, open-label pilot study.

• The Hopkins Verbal Learning Test (HVLT) assessed verbal learning and memory.
• The Grooved Pegboard Test assessed fine motor ability and hand-eye coordination.
• The Controlled Oral Word Association Test (COWAT) assessed verbal fluency.
• The Trailmaking Test, Parts A and B (TMT-A & B) assessed visual attention, motor speed, and cognitive flexibility.
• The Brief Fatigue Inventory (BFI) assessed fatigue.
• The Hospital Anxiety and Depression Scale (HADS) assessed depression.
• The Functional Assessment of Cancer Therapy-Brain (FACT-BR) assessed cancer-related quality of life for patients with brain tumors
• The Barthel Index assessed functional status.
• The Eastern Cooperative Oncology Group (ECOG) performance status measured general well-being; scores range from 0 (indicating perfect health with no restriction of activities) to 5 (indicating death). 
• The National Cancer Institute Common Toxicity Criteria (CTC), Version 2.0 scored the severity of detected side effects.

Fatigue (as measured by the BFI) was improved at week 2 for 46% of participants; at week 4, 75% had a significantly improved score (p = 0.025). Functioning (as measured by the FACT-BR) showed an improvement in all subsets of well-being at weeks 2 and 4 (p < 0.05) except social/family. Depression (as measured by the HADS) declined significantly at weeks 2 and 4 (p < 0.001). 

Functional status (as measured by the Barthel Index) did not change, but overall ECOG performance status improved, with 40% of patients improving at least one level. Cognitive function was not significantly changed, although the TMT-B did show a trend of overall improvement. 

Modafinil did not significantly improve learning and memory, fine motor ability, verbal fluency, or executive function, but results are limited due to the small sample size.

• This was a pilot study addressing fatigue, with cognitive function measured as a secondary outcome.
• The study had a small number of participants, with a drop-out ratio of 30%.
• The study had an open-label design.
• There was no control group. 
• Results for improvement on the TMT-B may be due to Type I error, given the multiple tests (multiple comparisons) examined in this trial.
• The study had limited cognitive assessment.
• The issue of practice effects was not addressed in a repeated measures study.

To compare the efficacy and safety of a pegfilgrastim biosimilar to reference pegfilgrastim

Patients were randomized to receive 6 mg of either reference pegfilgrastim or a biosimilar. The colony-stimulating factor (CSF) was given on day 2 of each cycle. ANC was measured on day 1 of cycle 1, then daily until recovery after nadir or until day 15. A margin of one day of neutropenia was established as the margin for noninferiority analysis.

• N = 275   
• MEAN AGE = 48.9 years
• FEMALES: 100%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Patients with breast cancer receiving docetaxel, doxorubicin, and cyclophosphamide (TAC) chemotherapy 

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

• PHASE OF CARE: Active antitumor treatment

• Noninferiority, randomized, controlled trial

• Consecutive days of neutropenia 
• Depth of absolute neutrophil count (ANC) nadir
• Days to ANC recovery
• Infections

All study outcomes were similar in both groups. Over 95% of both groups had musculoskeletal adverse events, including bone pain, myalgia, arthralgia, and back pain (13.7%–16.1% of patients).

The CSF biosimilar evaluated here demonstrated similar efficacy and safety to that of the reference pegfilgrastim.

Pegfilgrastim and the CSF biosimilar evaluated were shown to be therapeutically equivalent.

To determine if acute exercise reduces state anxiety in breast cancer survivors

Participants recruited were randomly assigned to a light or moderate intensity group and were asked to complete both moderate and light intensity exercise on two different days. Exercise sessions were done by cycling. Prior to exercise, questionnaires for anxiety and self-efficacy were completed. Participants cycled for 20 minutes, staying with standardized heart rate ranges as defined for light and moderate intensity. Questionnaires were repeated after each exercise session following an eight-minute rest.

• The study reported on a sample of 50 participants: 25 breast cancer survivors and 25 age-matched women without a cancer diagnosis.
• Mean participant age was 59 years in the breast cancer survivors and 56 years in the other women.
• Average time since diagnosis of breast cancer was five years.
• Of the sample, 40% had at least a bachelor’s degree and 80% were married or living with a partner.

• Single site
• Canada

The study has clinical applicability for late effects and survivorship.

A randomized, experimental, repeated-measures design was used.

• Spielberger State Anxiety Short Form
• Self-efficacy questionnaire adapted from a previous study: A total efficacy score was calculated by summing confidence ratings by the respondent within a possible score of 100 (reliability – 0.91).

There were no differences between day 1 and 2 for anxiety and self-efficacy. Repeated measures ANOVA on anxiety showed a main effect for time (p < 0.01), with anxiety decreasing across the time of exercise. The intensity of the exercise was not significant. There were no differences between breast cancer survivors and others. Self-efficacy measures showed a main effect for time (p < 0.01), but no differences between breast cancer survivors and others or between exercise intensities. Breast cancer survivors and others reported similar pre-exercise state anxiety levels. There was a significant reciprocal relationship between self-efficacy and state anxiety both pre- and post-exercise (p < 0.05).

Exercise appears to have a short-term effect in reducing anxiety and increasing perception of self-efficacy.

• The study had a small sample, with less than 100 participants.
• The study did not include control observations.
• The study period and intervention was very brief, consisting of only two days of exercise and observations.
• Utility of findings is questionable.
• Participants were generally physically fit and may have been biased toward exercise, limiting applicability of findings.

Studies with longer-term exercise interventions and in participants with higher levels of anxiety may be helpful in exploring these issues. Long-term findings suggest that the specific approach to management of anxiety during the cancer diagnostic phase does not appear to significantly impact anxiety and depression in women with low-risk abnormal findings. The timing of depression might suggest that extended follow-up after diagnostic testing and treatment may be associated with depression for some women. Which of the strategies examined here offer the best balance between benefits and harms is a matter of continuing debate.