To evaluate the effects of alvimopan on postoperative gastrointestinal (GI) function and length of hospitalization.

Alvimopan is an investigational opioid antagonist with limited oral absorption that does not readily cross the blood-brain barrier and, therefore, acts on the peripheral opioid receptors in the GI tract without affecting analgesia in patients taking opioids. Doses used in the study were 1 mg and 6 mg by mouth. On the day of surgery, patients were randomly assigned in equal proportions to one of three arms using computer-generated randomization stratified according to type of surgery. The three arms were 1 mg of alvimopan, 6 mg of alvimopan, or an identical appearing placebo. Patients took the drug or placebo two hours before surgery and then twice daily postoperatively until the first bowel movement, until discharge from the hospital, or for a maximum of seven days. Patients were seen twice daily by the research team, from 6 am to 8 am and then from 4 pm to 6 pm.  At each visit, patients were asked about time of first passage of flatus and first bowel movement. Oral intake was measured until patients could tolerate regular meals. Subjects were considered ready for discharge if they had adequate oral intake to discontinue IV fluids, GI function had returned (defined as passage of flatus), they were afebrile, and they were free of major complications.

• The study reported on a sample of 78 patients who were generally healthy or had well-controlled systemic disease.
• Patient age ranged from 18 to 78 years.
• Patients were undergoing abdominal surgery (partial colectomy: n = 15; total abdominal hysterectomy: n = 63) with general anesthesia.
• Patients were included in the study if they were receiving opioids postoperatively for pain.
• Patients were excluded if they had received epidural administration of analgesia, had used corticosteroids or immunosuppressive drugs concomitantly within two weeks or opioid analgesics within four weeks before surgery, were likely to receive nonsteroidal anti-inflammatory drugs (NSAIDs) after surgery, had Crohn disease, or had a history of abdominal radiation therapy or treatment with vinca alkaloids. 

• Washington University in St. Louis, MO
• January 4 to July 22, 2000

This was a randomized, placebo-controlled study.

• Enrollment of 26 patients per group provided 95% power to identify a significant difference of one day in time to fitness for discharge between the 6-mg dose group and the placebo group at an alpha level of 0.05 with a two-tailed logrank test.
• Time to events (time in hours since end of surgery) was compared among groups using the logrank test. Other statistical analyses were described in detail.
• For patients who withdrew, administration of the drug or placebo was stopped; however, evaluation of the patients continued and all available data were entered into the analysis.
• Demographic data and type and duration of surgery were recorded.
• Primary efficacy outcomes were time to first passage of flatus, time to first bowel movement, and time until patient was ready for discharge.
• Secondary outcomes were time to first ingestion of solids, time until actual discharge, and visual analog scores (VAS) for nausea, abdominal cramping, itching, and pain.
• Severity of nausea, abdominal cramping, pain, and itching were also recorded using 100 mm VAS.
• Total daily use of opioids was also recorded.

• Twelve patients withdrew from the study (four in the placebo group and eight in the 1-mg dose group); however, none were from the 6-mg arm of the study.
• Time to recovery of GI function was significantly shorter in the 6-mg dose group than the placebo group.
• Median time to first passage of flatus decreased from 70 to 49 hours (p = 0.03), time to first bowel movement decreased from 111 to 70 hours (p = 0.01), and the time until patients were ready for discharge decreased from 91 to 68 hours (p = 0.03).
• Oral consumption and actual discharge occurred significantly earlier for the 6-mg dose group.
• VAS scores for pain, itching, and abdominal cramping were similar in the three groups. In contrast, nausea scores were significantly reduced in the 6-mg dose group compared with the 1-mg dose and placebo groups (p = 0.003).
• No vomiting occurred in the 6-mg dose group compared with 23% and 26% in the placebo and 1-mg dose groups, respectively (p = 0.03).

The 6-mg dose of alvimopan improved all major outcomes, with or without correction for the type of surgery. Analgesic efficacy of opioids was not affected by the study drug, and no adverse events occurred.

• The study was funded by the pharmaceutical company Adolor Corporation, a grant from the National Institutes of Health (NIH), and two other local funds.
• Two authors were employees of Adolor Corporation and contributed to the study design and statistical analysis.

To explore the effectiveness of colchicine in patients with slow-transit constipation not relieved with previous treatment.

Patients with refractory constipation were referred from gastroenterology clinics affiliated with Shiraz University of Medical Sciences in Iran. Patients initially were screened to rule out structural constipation, and transit time was measured. Patients were randomly assigned to colchicines 1 mg daily for two months (group A) or placebo starch capsule daily for two months (group B). Study assessments were done every two weeks for eight weeks.

• The study reported on a sample of 60 patients.
• Mean patient age was 38.94 years in group A and 35.47 years in group B.
• The study comprised 26 women and 4 men in group A, and 21 women and 9 men in group B.
• Patients had a diagnosis of constipation and slow-transit time; history of unsuccessful treatment with bulking agents, stimulant laxatives, and osmotic agents; and Rome II criteria validation of constipation diagnoses.

• Single site
• Outpatient
• Shiraz University of Medical Sciences in Iran

This was a double-blind, placebo-controlled, clinical trial.

Knowles Eccersley Scott Symptom (KESS) scoring system

• A significant difference (p = 0.0001) existed in two-month mean KESS scores for the colchicine group (11.67, SD = 3.91; baseline: 18.13, SD = 5.43) compared to the placebo group (18.66, SD = 3.72; baseline: 20.13, SD = 3.86).
• No significant side effects were reported in the treatment or placebo groups. 
• Open-label follow-up for one month with the placebo group showed a 90.48% significant symptom improvement (p = 0.0001) compared to original response rates.
• No relapse in symptoms were reported from the original colchicine group.

Colchicine administration showed effectiveness in select populations.

• The sample size was small (fewer than 100 patients).
• The study took place at a single site, used a selective referral source, and did not assess efficacy of colchicine in conjunction with chronic pain or chronic opioid use.

Colchicine may be effective for short-term use in the treatment of slow-transit constipation, but further studies are needed to assess its effectiveness in an oncology population with chronic opioid use.

STUDY PURPOSE: To summarize systematic reviews that compared the efficacy, tolerability, and safety of cannabinoids with placebo or other antiemetics among patients of any age with any type of cancer

TYPE OF STUDY: Systematic review

• FINAL NUMBER STUDIES INCLUDED = 6 systematic reviews
• TOTAL PATIENTS INCLUDED IN REVIEW = Not reported
• SAMPLE RANGE ACROSS STUDIES: Not reported
• KEY SAMPLE CHARACTERISTICS: All age groups were included (ages 3.5–82 years) with all types of cancers; cannabinoids included dronabinol (7.5–30 mg), levonantradol (1.5–3 mg), nabilone (1–7 mg), or whole plant extracts.

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

Moderate quality evidence exists that pharmaceutical cannabinoids are less tolerated and less safe than placebo or conventional antiemetics. Insufficient evidence exists to determine if cannabinoids are more efficient than newer antiemetics. The number needed to treat with cannabinoid compared to placebo or conventional antiemetics to achieve complete control of CINV is four patients. The number needed to harm with cannabinoid compared to placebo or conventional antiemetics is six patients.

A narrow range of patients achieve complete control of CINV with cannabinoid versus patients who experience harm with cannabinoids. Insufficient evidence exists regarding the efficiency of cannabinoids versus newer antiemetics.

• Mostly low quality/high risk of bias studies

Cannabinoids should be considered for the treatment of uncontrolled or breakthough CINV but not as a first-line antiemetic for CINV.

PHASE OF CARE: Multiple phases of care

This update includes information from 14 clinical trials (eight randomized) involving 2,899 patients published since 2009. The quality of evidence and the strength of recommendations were guided by criteria from the Infectious Diseases Society of America and the United States Public Health Service grading systems and are presented in table format.

Only eight of the 14 studies considered were randomized, controlled trials.

Unlike previous versions, the newest guidelines provide separate recommendations for allogeneic HSCT in the pre- and postengraftment phases and in the presence or absence of GVHD. If GVHD is present, posaconazole is considered the drug of choice while fluconazole use is discouraged. Because the labeling of antifungal compounds can vary by country, the guidelines may not necessarily follow approved indications. They do, however, reflect published evidence.

To determine the overall symptom benefit of various physical therapy (PT) modalities applied on patients with head and neck cancer and lymphedema

This was a retrospective chart review of 32 patients with head and neck cancer who participated in physical therapy from August 2008 to July 2010. Patients were excluded if three or more variables were missing from the chart.

• N = 20  
• AVERAGE AGE = 54 years (SD = 12 years)
• MALES: 80%, FEMALES: 20%
• KEY DISEASE CHARACTERISTICS: All patients received surgical treatment with radiation and/or chemotherapy. Patients had head and neck cancer-related lymphedema. 
• OTHER KEY SAMPLE CHARACTERISTICS: Information gathered included body mass index, alcohol use, tobacco use, chief complaints, physical examinations of lymphedema, measurements of head and neck pre- and post-PT, presence or absence and intensity of pain, PT modalities, and number of sessions. The average time span from diagnosis to the start of physical therapy was 65.4 months (SD = 26 months).  

• SITE: Brazilian Institute of Cancer Central
• SETTING TYPE: Outpatient physical therapy
• LOCATION: Brazil

• PHASE OF CARE: After physical therapy

This was a retrospective study. The authors conducted a chart review of 20 patients who participated in physical therapy for complaints of swelling and pain related to head and neck surgery.

• Physical examination for assessment of lymphedema with a tape measure
• Occurrence and intensity of pain (Visual Analog Scale [VAS] from 0–10)
• Physical therapy modalities
• Number of physiotherapy sessions

• 100% of patients received program education.    
• 85% of patients experienced pain. This measure reduced to 70% by the end of the study.  
• Pain intensity reduced from 7.8 (SD = 2.2) to 3.6 (SD = 1.6) on the VAS (p < 0.001).
• Lymphedema volume reduction was successful (p < 0.05).  
• Modalities varied and included strategic manual lymphatic drainage versus physiologic manual lymphatic drainage (85%).
• Facial exercises were done by 75% of patients.
• Shoulder and neck exercises included stretching (80%), strengthening (55%), and range of motion (45%). 
• The average number of sessions was 23.9 (SD = 14.8) twice per week.  
• Compression therapy recommendations were documented for 70% of patients.

This study examined variables retrospectively to assess which practices might prove meaningful in a prospective study of patients with head and neck cancer. Pain would be an important symptom to study because of the interval between diagnosis and referral to physical therapy. Multiple physical therapy modalities were used, and a study supporting this would be useful. The findings from this study provided valuable information regarding designing future prospective studies.

• Small sample (< 30)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment) 

The duration between diagnosis of disease and referral to physical therapy was greater than two years in most cases. Excellent pain assessment skills are needed for this patient population because stiffness and tightness are usually caused by fibrosis. Fibrosis is progressive and needs to be addressed early. Physical therapy might be beneficial in the management of lymphedema.

To assess the efficacy of Biafine cream in preventing grade 2 acute radiodermatitis.

• Biafine cream was applied twice daily to the skin within the treatment field, starting on first day of radiation therapy (RT) treatment and ending two weeks after RT.
• No application of ointment within four hours prior to RT was allowed.
• No other prophylactic agents were to be applied to the RT field during the course of RT.
• Application of ointment was permitted within four hours before RT.
• Patients were given general skin care recommendations at the start of RT.
• Patients who developed grade 2 radiodermatitis had the option to withdraw from study and be treated with other topical agents or to continue with Biafine cream.

• The sample was comprised of 60 women.
• Median age was 49 years (range 25–77).
• Patients had breast cancer and were treated with lumpectomy.
• Treatment lasted for five weeks, with a total dose of 5,000 cGy in 200 cGy fractions and no boost.
• Patients were treated on a 6-mv photon accelerator.
• All patients wer treated with concomitant adjuvant chemotherapy.

Sunnybrook Regional Cancer Centre, Toronto, Ontario, Canada

Skin within the RT field was examined before the initiation of RT, at weekly intervals, and at two and four weeks after treatment by a radiation oncologist or a dedicated radiation technologist.

The Skin Assessment Questionnaire was scored according to the National Cancer Institute of Canada skin radiation toxicity criteria.

The self-administered questionnaire incorporated items from the instrument developed for the Ontario Clinical Oncology Group trial of hypofractionated RT after lumpectomy in women with node-negative breast cancer.

The study was an exploratory, phase II, intervention trial.

• Maximum skin toxicity observed during the five-week course of treatment was:
  • Less than grade 2 toxicity (15%; n = 9)
  • Grade 2 (83%; n = 50)
  • Grade 3 (2%; n = 1)
  • Grade 4 (0%; n = 0).
• The majority of dermatitis was observed after three weeks of RT.
• Eight patients started Flamazine™ (Smith & Nephew, Inc.) cream with grade 2 desquamation.
• Most patients subjectively felt that Biafine cream was soothing.
• No treatment delays or interruptions were observed due to skin toxicity.

The majority of patients who underwent concomitant chemotherapy and RT for breast cancer developed grade 2 radiodermatitis with the use of Biafine cream.

• There was a wide range of RT start times from the start of chemotherapy.
• It was not possible to compare to a control group to determine comparative effects.

To provide a prospective evaluation of pneumatic compression therapy in patients with breast cancer-related lymphedema

During phase I, adjunctive intermittent pneumatic compression (IPC) was assessed for its role as a component of the initial decongestive therapy with previously untreated lymphedema. Phase II was a prospective study to evaluate adjunctive benefit to IPC for maintenance. All patients received standard decongestive lymphatic therapy, which included MLD, compressive wrapping, and decongestive exercises. Each patient received 10 days of daily decongestive lymphatic therapy. The study group had IPC applied to the affected arm daily for 30 minutes, in addition to the treatment as noted previously.

• Patients were included in the study if they presented with lymphedema related to breast cancer, defined as greater than 20% in volume compared to the other arm.
• There was a 12-week interval between cancer treatment and enrollment to study.
• Patients were excluded from the study if there was evidence of bilateral disease, breast cancer recurrence, active clinical infection, or clinically evident venous occlusion.

The study took place at Stanford University in California.

The study used a randomized prospective design.

• Assessments of limb volume, tissue elasticity, and joint mobility were performed at enrollment and on days 10 and 40 of the study.
• Water displacement volumetry was used.
• Skin tonometry was used to determine tissue elasticity.
• Goniometry was used to assess shoulder, elbow, and wrist joints range of motion.
• Data analysis was done using both paired and unpaired t-tests and analysis of variance.

In phase I, 23 women were recruited; 12 patients were randomized to group receiving DLT and IPC, while 11 were randomized to the group receiving DLT alone. After two weeks of treatment, reduction in volume of edematous arm was 45.3% for group 1 and 26% for group 2 (p < 0.05). Both groups showed no sign of improvement in skin elasticity study pre- or post-treatment. Also, 48% of patients had objective evidence of impaired range of motion at baseline. After initial therapy, joint mobility improved uniformly (p < 0.011) between both groups. In phase II, 27 patients were recruited. During a month of self-administered treatment, there was a mean increase in volume of the treated limb in group 1 with DLT alone. During the month of therapy, which included self-administered DLT and IPC, there was a mean volume reduction (p < 0.05). Skin elasticity showed no difference between the groups. Data collected poststudy showed that 20 of the 25 patients elected to continue using the IPC. Measurements showed additional reduction of limb volume.

IPC, when used as an adjunct to the other established elements of DLT, provides an enhancement of the therapeutic response.

Initial cost of pneumatic pumps might limit applicability, but researchers noted that documented improvement of lymphedema may offset the cost of care.

To investigate whether the combination of pneumatic pump with manual lymph drainage (MLD) compared to MLD alone in standard complex decongestive physiotherapy (CDP) treatment can improve outcomes in women with stage 2 lymphedema after treatment for breast cancer

Participants were randomly enrolled into 60-minute MLD or 30-minute MLD plus 30-minute intermittent pneumatic compression (IPC) followed by standardized components of CDP (compression bandaging, physical exercise, and skin care 10 times in a two-week period). Patient assessment was completed at baseline, beginning of therapy, end of therapy, and one and two months after the start of the therapy.

• The study sample (N = 27) was comprised of female patients with breast cancer who were assigned to the CDP group (n = 13) or the CDP and IPC group (n = 14).
• Mean age was 54.83 years in the CDP group and 56.60 years in the CDP and IPC group.
• Patients were included in the study if they were more than 12 months after surgery or adjuvant treatment.
• Patients were excluded from the study if they had any sign of local recurrence or distant metastases or if they were within the obligatory treatment-free period of one year.

The study took place at an outpatient setting at the Lymphedema Care Unit of the University of Szeged, Hungary.

The study used a randomized controlled trial design.

• Limb volume was measured using tape at every four centimeters.
• The percentage reduction in total arm volume at each point was calculated with the formula ∆V% = [(pre-treatment arm volume – post-treatment arm volume)/pre-treatment arm volume] × 100.
• Patients completed subjective symptom questionnaires measuring function, heaviness, tension, and pain as well as their effects on related activities.
• Percentage improvement in the subjective complains was calculated with the formula ∆S% = [(total sum of pre-treatment scores – total sum of post-treatment scores)]/total sum of pre-treatment scores] × 100.

Mean reductions in limb volumes for each group at the end of therapy and at one and two months were 7.93% and 3.06%, 9.02% and 2.9%, and 9.62% and 3.6%, respectively (p < 0.05 from baseline for each group and also between groups at each measurement). A significant decrease in the subjective symptom survey was found for both groups compared to baseline, but no significant difference between the groups was found at any time point.

The application of IPC with MLD provided a synergistic enhancement of the effect of CDP in arm volume reduction.

• The sample size was small, with less than 30 participants.
• The study took place at a single site.

More studies involved in multisite settings with large sample sizes are needed to duplicate the findings from this study.

To test the hypothesis that patients who received standardized training about pain would have fewer barriers to treatment, report lower pain, and be more likely to take prescribed opioids than patients who received a control training unrelated to pain

Patients were stratified by institution and ethnicity and then randomly assigned to control and treatment groups. Pain training included a videotape and review, with a nurse, of a handbook. The nurse focused on the concerns of the individual patient. Patients completed a checklist of eight common barriers to pain control, indicating those that he or she had wondered about. The nurse helped the patient  apply information to the patient's own situation. To assist in communication about pain, the patient then completed a checklist of things to tell the doctor. Patients were encouraged to use the checklist in communicating with the doctor and to complete a checklist any time pain was not well controlled or when other symptoms occurred. Control group patients received interventions similar in format, but these focused on nutrition. After 72 hours patients in both groups received telephone contact that reinforced training. By telephone investigators gathered patients' ratings of pain, nausea, and eating symptoms. Patients' initial training took 30–45 minutes. Follow-up calls lasted about 10 minutes. Patients completed outcome assessments at baseline and at one, three, and six months. At each time point, physicians and nurses rated patients' usual and worst pain, using the same 0–10 scale that patients used.

• Eighty-eight patients completed the study.
• Mean patient age was 55.5 years. Age range was 27–80 years.
• In the intevention group, 58% of patients were female and 42% were male. In the control group, 71% were female and 29% were male.
• The sample included multiple cancer diagnoses. Breast cancer was the most frequent diagnosis: Of all patients, 23%–31% had breast cancer. In the sample 77% had metastatic or systemic disease, and most had advanced-stage disease with a life expectancy of at least six months at the time of study entry. Of all patients, 90.5% were Caucasian. More than 50% of patients had attended some college or had earned a college degree. Baseline Eastern Cooperative Oncology Group performance status was similar in both groups, at a mean of 1.03–1.30.

• Multisite
• Outpatient
• Six urban and rural oncology clinics in the United States

Randomized blind controlled trial

• Barriers Questionnaire (BQ)
• Brief Pain Inventory (BPI)
• Memorial Symptom Assessment Scale (MSAS)
• Functional Assessment of Cancer Therapy-General (FACT-G)
• ECOG Performance Status (total daily morphine equivalent doses for pain control calculated from tables in Cancer Pain Guidelines)

From baseline the group that received training about pain had a greater decrease in barrier beliefs about cancer pain (p < 0.001), with a 0.3 point decrease, and a greater average decrease in usual pain (0.8 decrease, p = 0.03). At one month, the pain-training group reported 25% lower mean pain ratings. The pain-training group used higher doses of opioids than did the control group (p = 0.001). There were no significant differences between groups regarding worst pain, pain interference with function, or overall symptom severity. Authors noted differences between groups at one month, but there were no differences at three and six months. The pain-training group had greater narrowing of the gap between the patient’s self-assessment of pain and the nurse’s pain ratings (p = 0.001). The institution providing care was significantly associated with change in barriers to pain treatment (p < 0.001) and change in worst pain (p < 0.001). From baseline, pain interference with function (p = 0.02) was higher for nonwhites. Researchers found that, frequently, doses of medications were not re-evaluated and that patients had not told physicians about side effects or that they had stopped taking analgesics. Chart reviews presented no evidence of patients using the checklists in clinic visits or in communication with nurses and physicians.

The training intervention appeared to have only a short-term positive effect on patients' management of pain. Observations regarding related communications between patients and their professional care teams, along with significant differences in outcome by institution, point to the impact of providers in effective pain management.

• The study had a small sample size, with fewer than 100 patients.
• The sample included few nonwhite participants, and findings showed significant differences regarding ethnic covariates. These facts suggest that findings cannot be generalized to various ethnic groups.
• Although the study design included blinding of providers and those who obtained study data, authors suggest that contamination across the two groups was likely.
• Authors did not discuss patient supports or caregiver involvement in pain management.
• Authors did not describe the characteristics associated with the significant institution-related differences in outcomes.

Findings suggest that a training component may help patients self-manage pain and communicate with care providers. However, the single intervention in this study had only short-term effects that varied by institution. This points to the importance of the engagement of care providers in ongoing pain management and the need for future research to study combined patient-provider efforts. Consistent reinforcement of patient education and use of communication aids may improve long-term outcomes.

To evaluate the effects of a supervised outpatient physical therapy strengthening and conditioning program on symptoms and quality of life

The program included aerobic exercise and strength training. The first two sessions were individualized under the supervision of a physical therapist. Patients who needed additional assistance walking, transferring, or using equipment continued to attend one-hour individual sessions. Patients were placed into 90-minute group sessions. The program consisted of intensive work for eight weeks, then six months of maintenance training was offered for those who were interested. Study assessments were done at baseline and after eight weeks.

• N = 75
• MEAN AGE = 62.6 years (SD = 11.9 years)
• MALES: 34.7%, FEMALES: 65.3%
• KEY DISEASE CHARACTERISTICS: Various tumor types (breast and lung were most prevalent)
• OTHER KEY SAMPLE CHARACTERISTICS: 34.7% metastatic disease; 15.3% in active treatment; 26.7% working full- or part-time

• SITE: Single-site  
• SETTING TYPE: Outpatient  
• LOCATION: Minnesota, United States

• PHASE OF CARE: Multiple phases of care

Quasi-experimental

• Short Form 36 (SF-36)
• Six-Minute Walk Test (6MWT)
• MD Anderson Symptom Inventory (MDASI)

The results of the 6MWt were better on average at the end of eight weeks (p < 0.0001). Physical component scores on the SF-36 improved (p < 0.001) as did mental component scores after eight weeks (p < 0.005). At the end of six months, only physical component scores remained higher than reported at baseline. Fatigue (p = 0.003) and dyspnea (p = 0.007) were improved at eight weeks. After six months, fatigue (p = 0.0077), shortness of breath (p = 0.0005), and disturbed sleep (p = 0.045) were improved from baseline. Patients still in active treatment showed significantly less improvement. Those who showed the worst performance at baseline showed the greatest improvement.

The eight-week strengthening and conditioning program improved physical function, fatigue, dyspnea, and sleep disturbance in this study. Improvement was greatest among those who had the worst symptoms and physical performance statuses at baseline and among those who were not in active treatment.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Subject withdrawals ≥ 10%  
• Other limitations/explanation: Greater than 30% of participants withdrew from the study. There were significant differences for individuals still in treatment; however, the sample was too small to adequately analyze study sample subgroups. No information was provided about other relevant interventions that may have occurred during the six months of follow-up.

The findings of this study demonstrated the effectiveness of an exercise program on symptoms of fatigue, shortness of breath, and sleep disturbance among a variety of patients with cancer. These findings add to the large body of evidence about the efficacy of exercise.