• FINAL NUMBER STUDIES INCLUDED =  12
• TOTAL PATIENTS INCLUDED IN REVIEW = 358
• KEY SAMPLE CHARACTERISTICS:  Mean age of 8.4 years, age ranged from 1–19 years; 55% male participants; 120 participants from Greece; 62% Caucasian; majority had hematologic cancer; many studies were conducted during painful procedures such as lumbar puncture and venipuncture.

PHASE OF CARE: Multiple phases of care

APPLICATIONS: Pediatrics

Integrative interventions may be very effective for pain and anxiety in children undergoing cancer treatment. Integrative modalities, however, warrant further study with larger sample sizes to better determine their effectiveness in this population.

• No description existed of the time window during which data were extracted.
• Various interventions were combined and analyzed as a unit.
• Only included randomized controlled trials and thus reduced literature sample size
• The sample size for each intervention was small.
• The effect of each intervention is not clear.

This study provided some evidence that complementary modalities can help children undergoing cancer treatment or painful procedures. The usefulness of a particular method should be further examined.

The exercise intervention was a supervised, home-based, flexible training program in young and middle-aged patients with cancer shortly after curative chemotherapy. An exercise instructor designed the training program. The exercise period lasted approximately 14 weeks, with a minimum of two exercise sessions per week of at least 30 minutes. All types of activities were chosen, based on the patients’ wishes and opportunities. The intensity of the exercise was adjusted according to the patient’s subjective experience of tiredness. Data were collected at baseline and at three weeks (approximately 14 weeks).

The study reported on a sample of 111 patients (59 in the intervention group and 52 in the control group).

A randomized controlled trial design was used.

• Cardiorespiratory fitness (CRF)
• European Organization for Research and Treatment of Cancer Core Quality-of-Life Questionnaire
• Hospital Anxiety and Depression Scale (HADS)

CRF increased and fatigue scores decreased in the intervention group. There were no significant intergroup differences in mental distress or health-related quality of life. There were no statistically significant decreases in anxiety levels as measured by HADS.

The intervention required an exercise instructor.

Databases searched were MEDLINE, PubMed, EMBASE, Allied and Complementary Medicine (AMED), and PsycINFO. The dates encompassed by the search process were not specified by the authors.

Trials that provided data on the outcomes of physical activity in survivors of prostate cancer were identified. Studies that did not disentangle the effects of physical activity from a package of multiple interventions (e.g., physical activity combined with diet, counseling, etc.) were excluded. Studies that included survivors of prostate cancer among other cancer survivors without presenting separate results for survivors of prostate cancer were also excluded.

Six studies that examined the effects of physical activity in survivors of prostate cancer were identified. Of these studies, the physical activity interventions were performed during radiotherapy in one study and during androgen depletion therapy in five.  Four studies were randomized trials, whereas two were uncontrolled trials.

Outcomes were physical functioning, body composition, fatigue, and quality of life.

Four studies examined the effects of supervised exercise programs, whereas two investigated the effects of home-based exercise programs. Three studies tested a resistance exercise program; one tested a home-based walking program; one tested a group-based lifestyle program designed to increase physical activity; and one used a home-based intervention with walking, stretching, and resistance activities with biweekly supervised group-based booster sessions. The length of the exercise programs ranged from four weeks to six months, with a median of 12 weeks.

Sample sizes ranged from nine to 155 participants (median sample size = 48).

In four of the six studies in which fatigue was measured and reported, statistically significant improvements in fatigue were noted.  All studies demonstrated that physical activity was safe and feasible for survivors of prostate cancer receiving treatment.

The objective of the study was to review the effectiveness of the use of single tunneled, valved pleural catheters in the treatment of symptomatic recurrent malignant pleural effusion following failed chemical pleurodesis.

Two hundred seventy patients who underwent placement of a tunneled pleural catheter between January 2002 and December 2006 were identified after reviewing interventional radiology billing records. After subsequent review of inpatient and outpatient medical reports for each case, 63 were reportedly treated for dyspnea associated with recurrent malignant pleural effusion following failed pleurodesis. In the incidence of suboptimal drainage post-procedure, fibrinolytic therapy with tissue-type plasminogen activator (tPA) dissolved in saline was administered into the catheter to dwell for two hours in the pleural space prior to drainage and was repeated at one- or two-day intervals, if clinically required for optimal drainage and symptom relief. Catheters were drained every other day until the volume decreased to 50 mL, in which case it was drained every three days. Catheters were subsequently removed from patients who achieved durable symptom relief on three consecutive drainages during the three-day intervals with less than 50 mL of drainage and who had no radiographic evidence of re-accumulation. For those with larger drainage volumes, however, catheters were left in place for continued use.

• Sixty-three of the 270 identified patients underwent pleural catheter placement for treatment of dyspnea associated with recurrent malignant pleural effusion (68 were documented hemithoraces).
• The mean age was 61 years, with a range of 30-85 years.
• Of the sample, 30.2% were males, and 69.8% were females.
• Of the 63 patients identified, malignancy was as followed: breast (22), lung (14), ovarian (7), pancreatic (4), primary peritoneal (4), mesothelioma (2), esophagus (2), carcinoid (2), chronic lymphocytic leukemia (1), colorectal (1), melanoma (1), cervical (1), squamous cell (1), and adenocarcinoma of unknown primary (1).
• Nine patients had pre-existing pigtail drainage catheters prior to placement of the tunneled catheter.
   

This single-site study was conducted in both inpatient and outpatient settings in Interventional Radiology.

• Patients were undergoing long-term follow-up care.
• The study has clinical applicability for end-of-life and palliative care.
   

The study was a retrospective review.

Dyspnea was measured, but the scale or instrument used was not defined.

• Sixty of 63 patients experienced “immediate clinical improvement in dyspnea” following catheter placement. No clear symptomatic improvement was noted in the remaining three.
• Fifty-seven of 63 patients (90%) were discharged from the hospital with a tunneled pleural drain after a median of three days (range 0-29 days).
• Twenty-one of the 68 hemithoraces (31%) required subsequent fibrinolytic therapy to promote drainage of complex pleural effusions.
• One patient had the pleural catheter removed prior to discharge, while five patients died before discharge.
• Twenty-seven patients (43%) were discharged in two days or less.
• Those with longer hospital stays were due to treatment of other disease-related medical conditions.
• Symptomatic recurrence of pleural effusion occurred in one patient 19 days after tunneled pleural catheter removal requiring catheter drainage.
• Median survival following catheter placement was 64 days (range 34-164 days).
• Mean follow-up for survivors was 746 days.

The large majority of patients (95%) experienced prompt symptom relief and clinical improvement following tunneled pleural catheter insertion. Parynchymal lung disease or rapid progression of disease was reported among the patients who did not improve from catheter placement.

• The study had a small sample size of less than 100.
• Authors did not describe how dyspnea was measured and evaluated pre- and post-catheter placement, making it hard to quantify/gauge the extent to which patients experienced symptomatic relief of dyspnea.
• Authors were unable to analyze the durability of symptom relief due to lack of “uniformity” of clinical follow-up and documentation (i.e., regarding patients' drainage schedule, drainage volumes, symptoms, imaging).
   

Use of tunneled pleural catheters for the treatment of recurrent malignant pleural effusion appears to be an appropriate and beneficial intervention for patients suffering from dyspnea following failed pleurodesis. The majority experienced immediate symptomatic relief of their dyspnea following catheter placement, although one-third of cases may necessitate transcatheter fibrinolytic therapy for adequate drainage. As noted by the authors, it is less invasive and more cost-effective than more successful, though high-risk interventions such as decortication (which is 100% effective but associated with high morbidity and mortality and not recommended for this population), thoracentesis (which offers immediate symptomatic relief but is associated with 98%-100% recurrence within 30 days), or thoracoscopy with talc poudrage (which has a high success rate but is more invasive and requires general anesthesia). It is also worth noting the short hospitalization period reported for 43% of the patient population, who were discharged within two days of catheter placement and symptom relief. However, effectiveness for patients with progressive disease remains questionable.

The study explored a homeopathic approach to treatment of estrogen-withdrawal symptoms in women with breast cancer.

Active intervention was a homeopathic approach, which included a 60-minute consultation and the prescription of an individualized homeopathic remedy. A total of 25 remedies were used for the first prescription. Pulsatilla, Sepia, and sulfur were each used on more than three occasions for the first prescription.

The study enrolled: 45 participants who ranged in age from 34 to 71 years; just over half were aged 50–59 years.

• Inclusion criteria:
  • 45 consecutive patients seen at the outpatient clinic at Glasgow Homeopathic Hospital with breast cancer and estrogen withdrawal symptoms 
  • 32 participants were taking tamoxifen
  • 21 had undergone adjuvant chemotherapy
  • 20 were taking medications such as antidepressants and clonidine
  • 3 had metastatic disease at study entry 
• Exclusion criteria: None

This was a prospective observational study.

The study used a numerical self-rating scale, where 0 = no problem, and 10 = tremendous problem, to identify patient symptoms. Hot flashes were rated as the most common symptom (n = 38).

A data table showed significant improvement in hot flashes between baseline and last visit (p < 0.001).

The study used a small, convenience sample of consecutive patients, some of who were taking antidepressants (not specified) and clonidine, which may both be used to manage hot flashes. The length of study and schedule of follow up visits were not apparent. Assessment of hot flash frequency and severity was not the primary outcome measure of the study, only one of several symptoms assessed. Primary endpoint was the “effect on daily living” scores. Homeopathy regimens were not defined, which could pose a problem for study replication. Exact reduction in hot flashes was difficult to determine.

To examine the safety and efficacy of subcutaneous methylnaltrexone for treating opioid-induced constipation in patients with advanced illness.

Patients were randomly assigned to receive either methylnaltrexone 0.15 mg/kg or placebo subcutaneously every other day for two weeks. Patients were permitted to continue their baseline laxatives and could use rescue laxatives. By day 8, the study drug dose (methylnaltrexone or placebo) could be doubled if patients had fewer than three rescue-free bowel movements. Patients in both groups who completed the two-week study were eligible to enter an open-label extension phase. During the extension trial, methylnaltrexone 0.15 mg/kg was offered as needed every 24 hours for up to three months. Subsequent doses could be increased to 0.3 mg/kg if there was no defecation.

• The study reported on a sample of 134 patients aged 18 years or older.
• Median age was 72 years (range 34-93) in the methylnaltrexone group and 70 years (range 39-98) in the placebo group.
• The sample comprised 27 men (43%) and 36 women (57%) in the methylnaltrexone group, and 31 men (44%) and 40 women (56%) in the placebo group.
• Patients had advanced illness, such as terminal cancer or other end-stage diseases with a life expectancy of at least one month, as well as opioid-induced constipation. 
• Patients were receiving a median opioid dose of 100 mg of oral morphine equivalent. 
• More than 50% of study participants had a diagnosis of terminal cancer.

• Multi-site
• 27 U.S. and Canadian nursing homes, palliative care centers, and hospice centers

The study has clinical applicability for the end-of-life and palliative phases of care.

This was a two-week, double-blind, randomized, placebo-controlled phase III study with a subsequent three-month, open-label extension phase.

• Global Clinical Impression of Change (GCIC)
• National Cancer Institute common toxicity criteria (CTC), version 2.0
• Numeric pain rating scale (0 = no pain and 10 = worst pain possible)
• Modified Himmelsbach Withdrawal Scale

Efficacy Analysis: Double-Blind Phase

• Forty-eight percent of patients in the methylnaltrexone group, as compared with 15% of patients in the placebo group, had rescue-free laxation within four hours of receiving the first dose (p < 0.001 for all comparisons).
• Sixty-eight percent of patients in the methylnaltrexone group, as compared with 45% of patients in the placebo group, had three or more rescue-free laxations per week (p = 0.009).
• The median time to laxation after the first dose was 6.3 hours in the methylnaltrexone group and 48 hours in the placebo group (p < 0.001).

Pain Scores and Opioid Withdrawal

• Both groups had stable scores on the Modified Himmelsbach Withdrawal Scale and no change in pain scores. 

Adverse Events

• Similar percentages of patients in both groups had at least one adverse event (AE), of which abdominal pain and flatulence were the most common.
• Most AEs were rated by investigators as being mild or moderate. 

Open-Label Extension

• Eighty-nine patients entered the open-label extension phase.
• Response rates to methylnaltrexone were consistent during the extension.

Methylnaltrexone as administered in this study was effective in inducing laxation in patients with advanced illness and opioid-induced constipation, without compromising analgesia or triggering withdrawal symptoms.

Calculations showed that a total of 130 patients (65 in each group) would allow detection of a difference of 30% to 35% in the proportion of patients having a laxation response. However, only 106 patients (52 in the methylnaltrexone group and 54 in the placebo group) completed the study.

Subcutaneous methylnaltrexone seems effective in treating constipation in patients with advanced illness and opioid-induced constipation without compromising analgesia or causing withdrawal symptoms. In this study, more than 50% of patients had a diagnosis of cancer; therefore, conclusions can likely be extended to patients with cancer. In addition, patients in this study were receiving a median opioid dose of approximately 100 mg of oral morphine equivalent. Many patients with cancer receive a larger dose; therefore, further study with increased doses of morphine equivalent is warranted.

To test the effectiveness of two interventions, compared to usual care, in decreasing attitudinal barriers to cancer pain management, decreasing pain intensity, and improving functional status and quality of life (QoL)

Patients were randomly assigned to one of three groups: control, standardized education, or coaching. Patients in the education and coaching groups viewed a video and received a pamphlet about managing cancer pain. In addition, patients in the coaching group participated in four telephone sessions facilitated by an advanced practice nurse–interventionist who used motivational interviewing techniques to decrease attitudinal barriers to cancer pain management. Questionnaires were completed at baseline and at six weeks after the final telephone call. Authors used analysis of covariance to evaluate differences in study outcomes among the three groups.

• The sample was composed of 227 patients—that is, patients who completed the end-of-study evaluation.
• In the control group, average age was 58.7 years; in the education group, 62.5 years; in the coaching group, 61.8 years.
• Of all patients, 90.1% were male and 9.9% were female.
• In the sample the most common cancer types were lung, prostate, and head and neck cancers. Breast and colon cancers, myeloma, and mixed types made up the remainder of diagnoses.

• Multisite
• Six outpatient oncology clinics (four Veterans Affairs facilities, one county hospital, and one community-based practice)
   

• Phases of care: multiple phases of care
• Clnical applications: late effects and survivorship

Randomized clinical trial

• Attitudinal-barriers assessment: Authors chose the Barriers Questionnaire (BQ), a 27-item instrument, 0–5 scale, to measure barriers to cancer pain management. Barriers include concern about side effects, concern about tolerance, fear of addiction, fatalism, fear of disease progression, desire to be a good patient, fear of injections, and concern about distracting the physician from curing disease.
• Pain assessment: The study used the Brief Pain Inventory, a  0–10 scale self-report, to assess intensity and quality of pain, the extent to which pain relief was obtained, and the extent to which pain interferes with function.
• Functional status: The SF-36, a 0–100 scale, assessed eight health concepts (physical functioning, role limitations because of physical health problems, bodily pain, social functioning, role limitations because of emotional health problems, general mental health, vitality, and perception of general health). Higher scores reflect higher functioning.  
• QoL: The study measured four QoL domains (physical, social, emotional, and functional well-being) by means of the FACT-G, a five-point Likert-type scale, with each subscale summed to obtain a subscale score and all individual items summed to obtain a total score. Total score can range 0–112.
   

• Authors found no differences among the three groups in any of the subscale or total BQ scores.
• Assessment of measures at the second time point found no differences among the three groups in regard to pain intensity or pain relief. However, at the end of the study, authors noted significant differences in mean pain interference scores (p < 0.01).
• The SF-36 showed significant differences among the groups in general health, vitality, mental health, and the mental component (as measured by summary score). The coaching group had higher mental health component scores than did the control group.
• Authors noted no significant differences among groups in regard to any of the FACT-G subscales or total scores.
• Patients in the coaching group reported a statistically significant decrease in pain-related interference with function and improved ratings of vitality, mental health, and general health. Compared to standardized education, coaching was associated with clinical improvements in cancer pain management (decreased cancer pain intensity and improvement or stability in functional status and QoL).

Findings suggest that coaching may be beneficial to cancer pain management, especially as management relates to collaborative development of individualized care plans that decrease symptoms.

• The fact that more than 90% of the sample was male may be a limitation. 
• The study employed a convenience sample, a fact that may limit applicability to other oncology populations. 
• The study did not alter the amounts or types of analgesics prescribed. This fact may limit results.   
   

Focused sessions consisting of 30 minutes of motivational-interviewing coaching by an advanced practice nurse may improve the management of cancer pain and overall health outcomes.

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.