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.

To report the experience with a new technique, axillary reverse mapping (ARM), in patients scheduled for axillary lymph node dissection (ALND) and to evaluate its usefulness for reducing the incidence of lymphedema

For the intervention group, blue dye was injected subcutaneously along the intermuscular groove of the upper inner arm; radioisotope was injected subcutaneously in the interdigital webspace of the hand. All blue and radioactive lymph vessels and lymph nodes were recorded. Only unsuspicious ARM lymph nodes located in the lateral part of the axillary basin were preserved. All other level I and II axillary lymph nodes were removed. One follow-up was conducted at a median of 19 months.

• N  = 143 
• MEDIAN AGE = 58 years
• AGE RANGE = 29–88 years
• MALES: 2.1%, FEMALES: 97.9%
• KEY DISEASE CHARACTERISTICS: Patients with breast cancer undergoing ALND

• SITE: Single site 
• SETTING TYPE: Inpatient 
• LOCATION: Brust-Zentrum Zurich, Switzerland

• PHASE OF CARE: Mutliple phases of care

• Pre-post design

• Arm volume measured using water replacement method via an arm volumeter

ARM was performed in 143 patients subsequently undergoing ALND. ARM lymph nodes were successfully identified in 112 patients (78%). In 55 patients, at least one ARM lymph node had to be removed. In 14 of these, tumor involvement was confirmed. In 71 patients, one or more ARM nodes were preserved. During a median follow-up time of 19 months, no axillary recurrence was noted. Thirty-five of 114 evaluated patients developed lymphedema. Preservation of ARM lymph nodes did not significantly decrease the incidence of lymphedema

ARM is feasible for patients with node-positive breast cancer. However, the study found no evidence that it reduces the incidence of lymphedema.

• Risk of bias (no control group)
• Risk of bias (no random assignment)
• Other limitations/explanation: Single0site study, non-RCT design, no baseline arm volume measure, and borderline power of the sample size

Larger studies with rigorous design are needed to evaluate whether preservation of clinically unsuspicious ARM nodes is oncologically safe and effective in preventing secondary lymphedema in patients with breast cancer.

Determine whether treatment with calcium channel blockers prevented oxaliplatin-induced acute neuropathy

Retrospective chart review was conducted to obtain data, and analysis was performed to determine differences in neuropathy symptoms between patients who were and were not on calcium channel blockers.

• N = 69  
• MEAN AGE = 62 years for the control group and 70 years for the intervention group
• MALES = 100%
• KEY DISEASE CHARACTERISTICS: Colorectal cancer; no staging data provided
• OTHER KEY SAMPLE CHARACTERISTICS: 35% of patients in the calcium channel blocker group were diabetic.

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

PHASE OF CARE: Active antitumor treatment

Two-group,  retrospective, cross-sectional

• Acute neuropathy charts were reviewed for symptoms of acute neuropathy including cold hypersensitivity, perioral paresthesias, shortness of breath, difficulty swallowing, pharyngolaryngeal dysesthesia, throat and jaw tightness, and dysphonia.
• Chronic neuropathy was evaluated using change of chemotherapy schedule and addition of supplementary analgesics.

The incidence of acute neurotoxicity was lower in the calcium channel group; however, no differences existed related to chronic neuropathy.

Patients receiving calcium channel blockers may experience less acute neurotoxicity than those not receiving calcium channel blockers, but more well-designed studies are needed before any conclusions can be made.

• Measurement validity/reliability was questionable.
• Study design was retrospective.
• Study primarily focused on acute oxaliplatin-induced neurotoxicity, which is a unique side effect of oxaliplatin and distinctly different from chemotherapy-induced peripheral neuropathy, which is chronic and has a different presentation and trajectory.
• Patients were already on calcium channel blockers when they enrolled in the study.

More studies are needed before any clinical implications can be made.

To determine effectiveness of cognitive behavioral therapy (CBT) techniques in alleviating distress and pain in patients with breast cancer

• Databases searched PsycINFO, MEDLINE, CancerLIT, and CINAHL 1974–June 2004. Investigators completed manual searches of reference lists and published meta-analyses.
• Search keywords were anxiety, cognitive behavioral therapy, distress, depression, hypnosis, imagery, pain, relaxation, and treatment outcomes.
• Studies were included in the review if they
  • Were randomized controlled trials (RCTs) with no-treatment or standard-care controls
  • Provided data sufficient to allow calculation of effect sizes
  • Measured pain and distress
• Studies were excluded if they did not measure pain directly.

The search retrieved 61 studies. Investigators eliminated some on the basis of the exclusion criterion; meta-analysis involved 20 studies. Authors defined CBT very broadly: Interventions included relaxation; guided imagery; hypnosis; biofeedback; and approaches combining cognitive restructuring, skill trainingt, and other strategies to enhance problem solving and coping. Authors do not describe the specific procedure used to evaluate study quality.

• Across the 20 studies, the sample was composed of 1,703 patients. Sample range was 16–215 patients.
• Seven studies were included in the meta-analysis regarding interventions for pain. All patients in these seven studies, 474 patients over all, had breast cancer.

Authors noted that 69% of patients in treatment groups did better than controls with respect to pain. Regarding pain, effect size (d) was 0.49 (95% CI 0.09–0.90, p < 0.05). Subgroup analysis comparing individual versus group interventions showed that intervention format had no effect on pain.

Findings suggest that CBT techniques produced a small to medium effect, as defined by the study, regarding the reduction of the pain of women with breast cancer.

• Authors defined CBT very broadly, including such techniques as hypnosis and relaxation therapy, which would not usually be considered CBT approaches.
• The number of studies and overall sample size for analysis regarding pain was relatively small. Authors did not report heterogeneity.
• Though effect size was statistically significant, whether a reduction of 0.49 on a pain scale is clinically meaningful is unclear.

Findings suggest that, for women with breast cancer, CBT may be a helpful adjunct to pain management. This finding is limited by the broad definition of CBT that this study employed. This study determined effect size on the basis of statistics. Future studies should define the type of change that is meaningful to patients—that is, change in symptoms.