To determine whether pegfilgrastim reduces leukopenia and infectious complications in patients with recurrent glioma treated with teniposide and a nitrosourea

Patients received nitrosourea 90 mg/m² on day 1 and teniposide 60 mg/m² on days 1–3 of every cycle. Cycles were given every six weeks until progression. The control group did not receive prophylactic pegfilgrastim, and the intervention group received pegfilgrastim 6 mg subcutaneously 8–24 hours after the third teniposide infusion.

• N = 60
• MEDIAN AGE = 56 years (range = 27–72 years)
• MALES: 55%, FEMALES: 45%
• KEY DISEASE CHARACTERISTICS: Patients with recurrent glioma treated with teniposide and a nitrosourea

• SITE: Single site    
• SETTING TYPE: Multiple settings  
• LOCATION: Germany

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

Retrospective review of medical records of patients treated at a neuro-oncology hospital

• Absolute neutrophil count

The expected nadir of teniposide is between days 8–17, and the nadir caused by the nitrosourea is expected after day 35. Therefore, patients may have an early nadir (defined as the period before day 30) and a late nadir (defined as the period from day 30 and beyond). Pegfilgrastim is expected to be active between days 3–11. Pegfilgrastim decreased the number of patients who had grade 3 neutropenia during the early nadir (9% with pegfilgrastim and 31% in the control group, p = 0.04). However, there was no difference in the rate of grade 4 neutropenia during the early nadir. Pegfilgrastim did not prevent any grade of neutropenia in the late nadir. Seven patients (27%) in the control group and six patients (17%) in the pegfilgrastim group were hospitalized because of myelosuppression or infections. There was no difference in the number of days these patients had to be hospitalized or needed intravenous antibiotics during the first two cycles of chemotherapy (p = 0.27 and p = 0.3, respectively).

The prophylactic administration of pegfilgrastim in patients treated with teniposide and nitrosourea for recurrent glioma did not reduce the frequency of grade 4 leukopenia, the need for antibiotics, or the number of days of hospitalization. It did reduce the incidence of grade 3 neutropenia in the nadir that occurred in the first 30 days.

• Small sample (< 100)
• Baseline sample/group differences of import
• Risk of bias (no random assignment)
• Risk of bias (sample characteristics)
• Key sample group differences that could influence results

The routine prophylactic administration of pegfilgrastim does not seem to provide a relevant benefit for nitrosourea and teniposide chemotherapy in patients with recurrent glioma other than reduction in the incidence of grade 3 neutropenia during the first 30 days.

Patients in the study group received 740 mg/m² IV amifostine prior to 200 mg/m² melphalan.

• The study reported on a sample of 41 patients, out of which 21 received amifostine and 20 were analyzed as controls.
• Patients were diagnosed with stage 3 multiple myeloma (MM) and receiving high-dose 200 mg/m² melphalan and autologous peripheral stem cell transplant.
• Median age of patients was 56 years with a range of 27–68.

This study was conducted betwen September 1999 and December 2001.

This was a prospective, comparative, non-randomized controlled, phase 2 trial conducted at a single institution.

• The World Health Organization mucositis scale was used.
• Opioid use was recorded.
• Delayed gastrointestinal side effects were reported.

• Fewer patients in the amifostine group experienced grade 2–4 mucositis (33% versus 65%, p = 0.047).
• No cases of grade 3-4 mucositis were reported in the amifostine arm.

• The sample size and study population were small.
• A large number of patients experienced emesis (43%).
• Limited mucositis data was included.

To determine effect of deodorant use on acute skin toxicity and quality of life during radiation therapy

Patients were randomly assigned to the deodorant group or the no-deodorant group. Prior to randomization, participants were stratified by presence of axillary radiation therapy and adjuvant chemotherapy. The deodorant group was instructed to use the product daily during radiation therapy. Only deodorant without aluminum was permitted. Deodorant use stopped only if grade 3 or greater radiodermatitis was evident.

• The sample was comprised of 84 female patients with breast cancer (stages 0–3. 
• Mean age was 59.9 years (SD = 10.6 years) in the deodorant group and 58.8 years (SD = 10.0 years) in the no-deodorant group.

The study took place at the Hotel-Dieu de Quebec Centre at Hospitalier Universitaire de Quebec in Quebec, Canada.

The study used a randomized, blinded trial design.

• Patients were evaluated using the Radiation Therapy Oncology Group acute skin toxicity criteria.
• During each visit, a photo of axilla was taken and patients completed questionnaires to evaluate symptoms.
• To evaluate pain and pruritus, the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0 was used.
• Sweating and discomfort were evaluated with an in-house scale.
• Quality of life was evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire.

In the deodorant versus the no-deodorant group, grade 2 axillary radiodermatitis occurred in 22.5% versus 29.5%, respectively (p = 0.019). Axillary moist desquamation was 10.0% versus 18.2% in the deodorant versus no-deodorant group, respectively (p = 0.003). Grade 2 breast radiodermatitis occurred in 30% versus 34.1% of the deodorant versus the no-deodorant group, respectively (p = 0.049). No grade 3 or 4 toxicity radiodermatitis was observed. Discomfort to axilla was 15% versus 25% in the deodorant and the no-deodorant group, respectively (p = 0.004). Moderate-to-severe pain was reported by 22.5% of the deodorant and 27.3% of the no-deodorant group (p = 0.031), Pain to the axilla region was seen in 7.5% versus 13.6% of the deodorant versus the no-deodorant group, respectively (p = 0.002). Axillary pruritus was self-reported by 7.5% and 20.5% of patients in the deodorant and the no-deodorant groups, respectively (p = 0.0002) . Breast pruritus was reported in a greater proportion of patients in deodorant (75%) than no-deodorant group (50%) (p = 0.19).

No evidence was found to prohibit deodorant use (without aluminum) during radiation therapy for breast cancer.

Findings were only for deodorants that did not contain aluminum, and it is not known if there would be any differences with different types of deodorant used.

To evaluate the efficacy and tolerability of controlled-release (CR) oxycodone as first-line therapy in patients with chronic pain not relieved by nonsteroidal anti-inflammatory drugs (NSAIDs).

Patients with NSAID-refractory chronic pain were treated with oral oxycodone CR twice daily for at least 28 days. Dosage was individualized for each patient and up-titrated over the first week of treatment. Primary end point was reduction in numeric rating scale (NRS) for pain. Secondary end points were tolerability, quality of life, and patient assessment of treatment efficiency.

• The sample was composed of 309 patients.
• Mean patient age was 67.1 years. Age range was 31–94 years.
• Of all patients, 50% were female and 50% were male.
• All patients had moderate to severe cancer or noncancer pain (that is, pain rated 4–10 on the 0–10 NRS). Of all patients, 24.3% had somatic pain, 14.1% had neuropathic pain, 8.2% had visceral pain, and 53.4% had mixed pain. Patients had had no previous or ongoing treatment with opioids.

Multisite

Prospective

• Numeric Rating Scale (NRS)
• Brief Pain Inventory (BPI)

Data revealed a significant decrease (57%) in pain intensity during the first week of therapy: a  decrease in NRS pain score from 7.85 + 1.4 to 3.35 + 1.8 (p < 0.00001). Overall, by the end of the study, NRS pain score had decreased 72.3% from baseline. Quality of life improved significantly (p < 0.005) during oxycodone therapy, and 91% of patients rated the treatment as effective or very effective.

Historically, according to guidelines of the World Health Organization, oxycodone CR has been reserved for step 3 of treatment. This study examines earlier use of oxycodone CR in the management of chronic cancer and noncancer pain, as a first-line treatment after NSAIDs. The results of this study warrant consideration because earlier, more effective pain control enhances quality of life.

The study has a risk of bias due to no appropriate control group.

Pain management must be individualized. Controlled-release opioids may be useful as an intervention after NSAIDs. However, randomized control-group research comparing the results of studies that use CR opioids in step 2 would be of value.

To test the effects of intraoperative IV lidocaine on postoperative recovery

Prior to surgery, patients were randomized to receive lidocaine infusion or placebo of normal saline. This was given as a bolus prior to anesthetic induction in a dose up to 1.5 mg/kg. Two hours after arrival to the post-anesthesia care unit (PACU), patients were given an infusion of lidocaine or placebo at 2 mg/kg per hour for up to two hours or discharge from the PACU. All patients had general anesthesia, but specific agents used and postoperative analgesia were not standardized. Pain was assessed at 2, 24, and 48 hours, and opioid consumption was documented.

• N = 71   
• MEAN AGE = 53.5 years
• FEMALES: 100%
• CURRENT TREATMENT: Other
• KEY DISEASE CHARACTERISTICS: All were undergoing mastectomy for breast cancer, and 64% had simple mastectomy.
• OTHER KEY SAMPLE CHARACTERISTICS: No differences existed between groups in duration of surgery.

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

• PHASE OF CARE: Active antitumor treatment

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

• Numeric Pain Rating Scale (NPRS)

There were no significant differences between groups in pain scores or overall opioid consumption.

Perioperative IV lidocaine was not shown to reduce postoperative pain or opioid consumption.

• Small sample (< 100)
• Findings not generalizable
• Efficacy may depend upon the extent of surgery and associated levels of pain.

Use of perioperative IV lidocaine did not have an effect on postoperative pain or need for analgesics in this study. Study investigators pointed out that there are some mixed findings in this area, and that efficacy of perioperative infusion of anesthetics may differ according to the extent and type of surgery.

• Placebo or interleukin-11 (IL-11) 25 mcg/kg or 50 mcg/kg subcutaneous (SC) daily beginning at day one (after completion of chemotherapy) and continued for 14–21 days or until platelet count of greater than or equal to 100K
• Study during one cycle of chemotherapy. Platelet checked three times per week (nonconsecutive days); repeated daily if platelet count less than or equal to 50K. Platelets were transfused if the count was less than or equal to 20K.
• Had to start with platelet count greater than or equal to 100K
• Single donor and pooled donor platelets given
• Done as outpatient from December 1993–February 1995

• N = 93
• AGE: 17–73 years
• KEY DISEASE CHARACTERISTICS: Solid tumors of lymphoma, excluded radiotherapy-induced thrombocytopenia or chemotherapy given less than five days prior
• OTHER KEY SAMPLE CHARACTERISTICS: Patients who already had been transfused with platelets at least once (during the chemotherapy cycle immediately preceding the study) for severe thrombocytopenia related to chemotherapy (nadir counts less than or equal to 20K). Chemotherapy regimen was continued (same agent, doses, and schedule).

• SETTING TYPE: Multicenter (20 centers)

• Randomized, blind, placebo-controlled

• Determine whether patients required any platelet transfusions during the study cycle
• Successful outcome was no transfusion.

• Dose of 50 mcg = 30% did not require transfusion versus 4% with placebo (p < .05)
• Dose of 25 mcg = 18% did not require transfusion (p = .23)
• Side effects were fatigue and cardiovascular symptoms (e.g., atrial fibrillation, syncope).
• Five patients were discontinued before receiving any study drug; 82 patients were evaluable, and six patients were not evaluable.
• Median number of platelet transfusions was one with the 50 mcg group, two with the 25 mcg group, and three with the placebo group. Forty-one percent of patients who did not require transfusion were those with shorter chemotherapy times and the 50 mcg dose.
• Median duration of platelet count with 25 mcg and 50 mcg dosing was two days at less than 20K, seven days at less than 50K, 13 days at less than 100K, versus with placebo of five days at less than 20K, 10 days at less than 50K, and 14 days at less than 100K.
• Ecchymosis appeared in 21% at 50 mcg dose, 24% at 25 mcg dose, and 35% with placebo.
   

• Patients already had received platelet transfusions during chemotherapy cycle prior to study
• Studied during only one cycle of chemotherapy
• Chemotherapy (single and combo agents) cycles were less than five days.
• Started with platelet counts greater than 100K
• Variety of cancers (e.g., breast, lung, Hodgkin and non-Hodgkin, ovarian, and “other”)

To ascertain the frequency of neural blockade in certified palliative care units and by palliative care teams; to determine the efficacy of neural blockade interventions and explore the predictors of successful interventions

Co-researchers from 120 certified palliative care units and 20 palliative care teams reported on all patients who received neural blockade for pain control 2002–2003.

• The sample was composed of 136 patients. Authors studied 162 neural blockade interventions.
• Mean patient age was 59 years.
• Of all patients, 37% were female and 63% were male.
• Patients were adults with cancer who required neural blockade to manage pain refractory to standard pharmacologic management. Of all patients, 47 patients (35%) had colon or rectal cancer, 19 (14%) had uterine or ovarian cancer, 18 (13%) had pancreatic cancer. (Authors provide additional diagnoses.) Eight patients underwent two neural blockade procedures. Four patients underwent three procedures. Procedures included epidural nerve block with local anesthetics and/or opioids, neurolytic sympathetic plexus block, and intrathecal nerve block with phenol.

• Multisite
• Japan

Retrospective chart review

• Support Team Assessment Schedule
• Eastern Cooperative Oncology Group (ECOG) Performance Status Communication Capacity Scale (originally a validated five-item observer-rating scale), to quantify communication capacity in terminally ill patients (The scale includes ratings 0–3, with 0 or 1 indicating that the patient can achieve clear communication of complex or simple content.)
• Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, to grade grading delirium

All types of neural blockade studied—epidural, plexus, and intrathecal—were associated with reduction in pain intensity, improvement in performance status, and decrease in opioid consumption. No type was associated with significant improvement in communication level or decrease in delirium. Groups receiving plexus block or epidural experienced an improvement in performance status. Patients in the epidural and intrathecal groups reduced use of opiods, but patients in the plexus block group did not.

Of patients receiving palliative care services in Japan, 3.8% required neural blockade for pain control. The percentage is similar in Western countries. Study findings suggest that neural blockade can decrease pain intensity, improve performance status, and decrease opioid consumption, without causing serious adverse effects. Of 19 patients who had a neural blockade, six showed a decrease in delirium.

• This study was a retrospective chart review. Though researchers used a standardized data-collection sheet, not all charts may have included all the data requested.
• Data related to communication level and delirium were not collected in terms of metabolic or progressive disease symptoms. This practice would have aided assessment of change related to these two factors.
• Participating institutions were selected on the basis of convenience.
• Long-term efficacy was beyond the intent of the study.
• No patients received intrathecal opioid therapy, which was not a common practice in Japan at the time of the study.

Neural blockade may be a useful intervention for a select group of patients who are receiving inadequate pain control from traditional opioids.

STUDY PURPOSE: To determine the effectiveness of cryotherapy on oral mucositis in patients receiving myeloablative conditioning followed by bone marrow transplantation (BMT)

TYPE OF STUDY: Systematic review

PHASE OF CARE: Active antitumor treatment

Oral cryotherapy before, during, and after chemotherapy infusion reduced oral mucositis incidence, severity, and pain.  

Small number of studies was looked at. Three of the six studies were greater than five years old.

Cryotherapy is a simple, low-cost, effective way of decreasing mucositis in some patients. The proper administration of cryotherapy is important for the best results possible. Nurses need to understand the instructions of how and when to administer cryotherapy and enlist the patient's and caregivers' help in administering it.

To determine the efficacy and tolerability of intranasal fentanyl spray (INFS) in the treatment of cancer-related breakthrough pain

Eligible patients went through an open dose-titration phase to determine an effective individual dose of the study drug. In the double-blind phase, patients were given 10 “blinded” bottles containing either the determined dose of INFS or placebo. The bottles were in a randomly assigned sequence. Each patient self-administered a maximum of four doses per day. If relief was inadequate at 30 minutes or if a separate episode of breakthrough pain occurred within a four-hour period, patients could take their usual rescue medication for analgesia. After each treatment episode, subjects recorded relief scores at timed intervals and rated overall satisfaction by means of an electronic diary. Self-reported adverse events were recorded throughout the study, and the study clinician directly assessed nasal condition at the beginning and end of the study.

• Seventy-six patients completed the study.
• Mean patient age was 53.8 years (SD = 11.6 years).
• Authors did not report information about the gender of participants.
• Patients were not receiving active chemotherapy or radiation therapy and did not have unstable clinical conditions or rapidly escalating or uncontrolled pain.
• The mean baseline pain-intensity score was 6.89 (SD = 1.7) across INFS-treated episodes and 6.96 (SD = 1.83) for placebo-treated episodes.

• Multisite
• Outpatient
• The state of Georgia, United States

Randomized double-blind, placebo-controlled multiple-crossover study

• Numeric pain-intensity scale (0 = no pain, 10 = worst possible pain)
• Five-point pain-relief scale
• Nasal assessment questionnaire, to identify of nasal symptoms

• Of patients in the open label-titration phase, 72.8% found an effective and tolerable dose of IFNS. Of patients who withdrew from the titration phase, 11.4% withdrew because of adverse events or lack of efficacy.
• The analgesic effect of INFS was consistently better than that of placebo at all time points measured. At 15 minutes from the beginning of the pain episode, 73% had an observed pain-reduction effect (P < 0.0001 compared to placebo). Reduction of pain in INFS episodes was clinically meaningful (pain-reduction score ≥ 2-point reduction) at all time points (p < 0.0001 versus placebo)
• Of all episodes of breakthrough pain treated with INFS, 90% did not require additional rescue medication. Of all episodes of breakthrough pain treated with placebo, 80% required rescue medication (p < 0.001).
• Speed of relief was better with INFS than with placebo (p < 0.0001).
• The most common side effects of INFS were vomiting, nausea, dizziness, epistaxis, nasopharyngitis, somnolence, and headache. Most nasal events were mild.

INFS is effective for the relief of breakthrough cancer pain for some patients and, as administered in this study, is not associated with severe and prevalent adverse effects.

• The study has a small sample size, with fewer than 100 patients.
• The duration of the study was short, so efficacy and tolerability over a long term are unknown.
• The study comprised a relatively healthy population, and patients were not under treatement. As a result, the results of this study may not be applicable to other patients and other situations.
• The length of time a patient had chronic pain prior to study participation is not provided, and the range of regular opioid doses is not provided. These factors may have effects.
• The fact that the fentanyl was associated with more taste disturbance than was placebo suggests that patients may not have been unaware of the drug they were using.

For the short term, INFS is effective for the management of breakthrough pain episodes for some patients with cancer. Nurses should be aware of the need for assessment of nasal symptoms with INFS use. The fact that slightly more than 20% of patients did not find an effective and tolerable dose of INFS is a reminder that effective pain management, which includes management of breakthrough episodes, needs to be highly individualized to be effective. INFS appears to be a useful part of the set of strategies to manage cancer-related pain. Despite strong evidence from this study, in regard to the immediate effect of INFS, research has not ascertained the effects of long-term INFS use.

To evaluate the effectiveness of an herbal mouthwash containing Matricaria recutita and Mentha piperita to placebo for the control of oral mucositis among patients undergoing hematopoietic cell transplantation (HCT)

Patients were randomized to placebo or the herbal mouthwash. The herbal mouthwash was formulated with 1% peppermint oil, 1% dried extract of Matricaria recutita (chamomile) and ethanol. The placebo was similar in taste, odor, and color. Both formulations were tested to ensure sterility. One week prior to HCT, patients began the intervention, diluting the mouthwash in preboiled water. They were instructed to gargle with the mouthwash for 30 seconds and then spit it out. The mouthwash was used three times daily after meals. All patients were instructed in oral care and used salt and chlorhexidine mouthwashes three times daily.

• N = 60   
• MEAN AGE = 36.44 years
• MALES: 44.3%, FEMALES: 55.7%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: All were undergoing HCT. Cancers were leukemia, lymphoma, and multiple myeloma.

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

PHASE OF CARE: Active antitumor treatment

Double-blind, placebo-controlled, randomized, controlled trial

• Common Terminology Criteria for Adverse Events (CTCAE) mucositis scale
• Oral mucositis daily assessment
• Symptom severity measured on 0–10 numeric rating scale

No difference in incidence of oral mucositis or time of onset existed between groups. The duration of mucositis was less in the treatment group (p < 0.0001). Patients in the treatment group had lower maximum grades of mucositis (p = 0.006) and lower average daily mucositis grades (p = 0.04). Pain (p = 0.009), oral dryness (p = 0.04), and dysphagia (p = 0.0009) were less severe in the treatment group. Fewer patients in the treatment group required additional treatments, such as narcotics for pain or parenteral nutrition (p < 0.05).

Oral rinses with a chamomile and peppermint mouthwash was associated with a lower severity and shorter duration of oral mucositis.

• Small sample (< 100)
• Measurement/methods not well described
• Timing of study measures and analysis of repeated measures were not well described.

The findings suggest that an oral rinse containing chamomile and peppermint may be helpful for the management of oral mucositis in patients undergoing HCT. Oral mucositis is a common toxicity with high-dose chemotherapy, and few interventions have been shown to be effective. Additional research on the use of chamomile for oral rinses is warranted, and research should include evaluation of oral rinses as an adjunct to other interventions shown to have efficacy.