To determine if the probiotic Colon Dophilus is able to prevent irinotecan-induced diarrhea in patients with metastatic colon cancer

Placebo versus probiotic Colon Dophilus. The probiotic was given three times per day for 12 weeks while the patient received irinotecan.

• N = 46  
• AGE = 42–81 years
• MALES: 52.2%–60.9%, FEMALES 47.8%–39.1%
• KEY DISEASE CHARACTERISTICS: Metastatic colon cancer

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

• PHASE OF CARE: Active antitumor treatment

• Placebo controlled stratified, double-blinded trial of study medication administered to patients with metastatic colon cancer starting therapy with an irinotecan-based chemotherapy regimen.

• Study diary 
• Common Terminology Criteria for Adverses Events (CTCAE)

Probiotics reduced the incidence of grade 3 or 4 diarrhea compared with placebo (0% versus 17.4% for control group). Patients who used probiotics reported using fewer antidiarrheal medications.

Probiotics appear to be safe and may be of use in irinotecan-induced diarrhea.

• Small sample (less than 100)
• Baseline sample/group differences of import
• Measurement validity/reliability questionable
• Early study termination due to poor accrual
• Critical/fatal flaw–data on adherence/protocol compliance to probiotic consumption were not collected

More research on the use of probiotics and irinotecan-based chemotherapy is needed.

STUDY PURPOSE: To assess the efficacy of topical corticosteroids in the prevention of acute radiation dermatitis compared with placebo, other topical medication, or no treatment

• FINAL NUMBER STUDIES INCLUDED = 6
• SAMPLE RANGE ACROSS STUDIES: The study sample size spectrum for both arms of the studies ranged from 23–169 participants.
• TOTAL PATIENTS INCLUDED IN REVIEW: 413
• KEY SAMPLE CHARACTERISTICS: All studies focused on female patients with breast cancer, ages ranging from 27–89 years, receiving post-operative radiotherapy after modified radical mastectomy or breast conservation surgery with an indication for post-operative radiotherapy. Radiotherapy was administered for an average of 25–39 days at a dose of 50–60 Gy.

PHASE OF CARE: Active antitumor treatment

Together, the studies showed that the prophylactic application of topical corticosteroids reduced the incidence of moist desquamation and lowered the mean acute radiation dermatitis scores.

• Use of different steroid medications, potency, and routes of application
• Differing skin toxicity scales used (e.g., Radiation Therapy Oncology Group, Common Terminology Criteria for Adverse Events)
• Lack of blinding in some studies
• Only six studies written in English were included in all levels of the analysis
• Breast was the only site evaluated

The results of this systematic review and meta-analysis show that topical steroids may be likely to reduce the incidence of radiotherapy-induced moist desquamation of the breast. Additional well-constructed studies consistently implementing blinding and testing the same steroid formulation and route of administration are needed. Studies examining other radiation treatment sites are indicated.

To determine if there is an adverse effect to irradiated skin when patients use their normal skin care regimens

Two consecutive groups of patients received tangential breast irradiation. The first group (group A) used the traditional skin care advice of using warm water only, avoiding the use of all lotion, soaps, and deodorants in the treatment field. The second group (group B) continued with their normal skin care regimen with no product restriction. Patients and therapists scored the skin reaction weekly and three weeks after treatment.

• The study sample was comprised of 156 patients with breast cancer who received treatment in group A (n = 94) or group B (n = 64).
• Twenty-two percent of patients were also receiving tamoxifen.
• Patients were treated on cobalt units or a 6 MV linear accelerator.

The study used a prospective trial design.

• Erythema, dry desquamation, patchy desquamation, and moist desquamation were scored weekly using a numerical scale from the researchers' institution.
• Level of discomfort, interference with normal activities, and use of analgesics for skin reactions was self-scored by patients weekly using a numerical scale.
• Treatment parameters, breast size, medical history, concurrent medications, nursing or medical interventions, and skin products used were documented.
• T-test statistical analysis method was used to establish if there was a significant difference in the mean score for the reactions in each group.

There were no significant differences found in skin assessment scores between groups. Reactions peaked at 7–10 days from completion of radiation. There was no difference in the skin scores between the two groups at that point. Patient self-scoring of the severity of the skin reaction revealed that group A consistently scored higher than group B, indicating greater level of problems.

There is no difference between the severity of skin reactions of patients using no products and those using their usual skin care products.

• The study had a risk of bias due to no random assignment.
• Skin scoring and patient self-report did not use standard scales.
• No testing was completed for validity and reliability of rating scale.
• No data were provided on the specific products patients used.

To determine the effect of tranexamic acid (TA) upon transfusion frequency and to explore the safety of TA in patients undergoing complex skull base neurosurgical procedures

The authors retrospectively examined records of patients undergoing complex skull base neurosurgical procedures. Patients were placed into one of two cohorts based upon administration of TA or not to determine the effect of TA on transfusion rates and TA-associated complications. Data were collected from patients undergoing the surgical procedure from 2001 to 2013.

• N = 503   
• MEAN AGE = TA: 49 years (SD = 13), no TA: 48 years (SD = 13)
• MALES: 40%, FEMALES: 60%
• CURRENT TREATMENT: Other
• KEY DISEASE CHARACTERISTICS: Complex skull base neurosurgery (55% acoustic neuroma and 25% meningioma) 
• OTHER KEY SAMPLE CHARACTERISTICS: TA not given until 2006

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: British Columbia, Canada

PHASE OF CARE: Active antitumor treatment

Retrospective, observational cohort study

Multivariate regression was used to identify predictors of transfusion.

The administration of TA was associated with a decreased incidence of transfusions (95% confidence interval [CI] [0.15, 0.65], p = 0.002). No evidence of an adverse event profile (95% CI) existed for either thrombotic events (adjusted odds ratio (OR) = –0.09, 95% CI [–3.5, 1.8]) or seizure activity (OR = 1.1, 95% CI [–1.7, 3.9]) associated with TA.

In patients undergoing complex skull base neurosurgical procedures, this retrospective observational study compared transfusion frequency and TA-related adverse events between two cohorts based upon the administration of TA. A significantly decreased frequency of transfusions was associated with the administration of TA; no significant increase in TA-related adverse events was reported between the two cohorts.

• Baseline sample/group differences of import
• Risk of bias (no random assignment)
• Risk of bias (sample characteristics)
• Unintended interventions or applicable interventions not described that would influence results
• Key sample group differences that could influence results
• The decrease in transfusions during the course of the study could be related to historical confounding. In addition, TA was not offered until 2006, so the cohorts were not equal. Also, the decision to administer TA was not random, neither was the dose standardized. 

Neurosurgical nurses caring for patients perioperatively may anticipate less need for transfusions in patients who receive TA perioperatively. However, the retrospective nature of this study needs confirmation of findings from future randomized, controlled trials.

To appraise the effectiveness and safety of a three-drug antiemetic prophylaxis treatment in patients with breast cancer receiving a regimen of ​5-fluorouracil, epirubicin, and cyclophosphamide

All patients received the same antiemetic prophylaxis regimen consisting of aprepitant (oral 125 mg on day 1 and oral 80 mg on days 2 and 3), palonosetron (0.25 mg IV on day 1), and dexamethasone (12 mg IV on day 1). The acute phase was defined as the first 24 hours after chemotherapy, and the delayed phase was defined as days 2–5 following chemotherapy. Complete response (CR) was defined as no vomiting or rescue treatment, and complete protection was defined as no vomiting, no rescue treatment, and no significant nausea. Total control was defined as no vomiting, no rescue treatment, and no nausea. Data were collected for five days following the administration of chemotherapy.

• N = 92  
• MEDIAN AGE = 55 years (range = 37–72 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Breast cancer

• SITE: Single site    
• SETTING TYPE: Outpatient    
• LOCATION: University of Florence, Largo

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

Cross-sectional, descriptive, single-arm design (design was not specifically mentioned in the article)

• Presence of nausea and vomiting
• Intensity of nausea
• Use of antiemetic drugs
• Additional symptoms

Only cycle 1 data were used in this study. In the acute phase, 89.1% of patients achieved CR, and 81.5% achieved CR in the delayed phase. Complete protection was achieved in 67.4% of patients in the acute phase and 62.0% of patients in the delayed phase. Total control was achieved in 52.2% of patients in the acute phase and 48.9% of patients in the delayed phase.

Prophylaxis consisting of aprepitant, palonosetron, and dexamethasone was safe, effective, and highly recommended in patients receiving anthracycline-based regimens (although it is not classified as a highly emetogenic chemotherapy by all international guidelines). Additional controlled trials are strongly needed to better define the optimal approach in emesis prophylaxis.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement/methods not well described

The majority of patients in this study experienced CR in the acute and delayed phases after chemotherapy administration. Triple-drug therapy was an appropriate intervention for chemotherapy-induced nausea and vomiting prophylaxis in patients with breast cancer receiving anthracycline and cyclophosphamide treatment.

To examine the efficacy of qigong or tai chi to alleviate treatment-related fatigue and disturbed sleep in men who were undergoing radiotherapy for prostate cancer

• N = 90   
• MEAN AGE = Qigong group: 62.2 years (SD = 7.4 years), light exercise: 65 years (SD = 5.9 years), wait-list control: 66 years (SD = 8.4 years)
• MALES: 100%  
• CURRENT TREATMENT: Radiation 
• KEY DISEASE CHARACTERISTICS: Prostate
• OTHER KEY SAMPLE CHARACTERISTICS: Thirty-three participants were in stage T2a or less, 19 participants were in T2b–T2c, and 14 were in T3a or greater. The majority of participants were also undergoing androgen deprivation therapy.

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: MD Anderson Cancer Center, Texas

PHASE OF CARE: Active antitumor treatment

Randomized, controlled trial

• Pittsburgh Sleep Quality Index (PSQI)
• Brief Fatigue Inventory (BFI)
• Expanded Prostate Cancer Index Composite (EPIC) 

This study did not show improvements in fatigue scores reported in any group either during treatment or after. Improvements in sleep duration was reported by those in the qigong group when compared to the light exercise group and the wait-list control. Sleep disturbance remained higher than clinical cutoff for all groups. Adherence to attendance at intervention in all classes was 64%. Additional practice at home after radiotherapy ended was not assessed.

Men undergoing radiotherapy for prostate cancer are able and willing to participate in physical activity interventions, such as qigong and/or light exercise. Fatigue and sleep disturbance are common symptoms experienced by men undergoing radiotherapy for prostate cancer and may persist after treatment is complete. However, qigong improved sleep duration for participants during radiotherapy treatment. This study did not detect improvements in fatigue or sleep disturbance that were sustained over the three-month period of the study.

• Small sample (< 100)
• Findings not generalizable
• Intervention expensive, impractical, or training needs
• Subject withdrawals ≥ 10%

No side effects were reported in either intervention group (qigong or light exercise).

• Databases searched were Cochrane Central Register of Controlled Trials (CENTRAL) (2nd quarter 2002), MEDLINE (January 1966–March 2003), EMBASE (January 1980–2nd quarter 2002), LILACS (January 1984–December 2001). Investigators also searched the reference lists of relevant publications.
• Search keywords were neoplasm, anti-inflammatory drugs, nonsteroidal, and pain.
• Studies were included in the review if they were published in any language.
• Studies were excluded if they involved animals.

The search retrieved 42 trials. Eight trials compared an NSAID with a placebo, 13 compared one NSAID with another, 23 compared an NSAID with an opioid or an NSAID-opioid combination, and 9 assessed the effect of increasing the NSAID dose. Sixteen of the 42 studies were conducted over seven days or longer, and 11 studies were single-dose studies. No study lasted longer than 12 weeks. Treatments studied included weak opioids, strong opioids, and agonist or antagonists. Nine studies examined dose range. Outcomes measured included differences in pain intensity, pain relief, and incidence and severity of adverse effects. Many studies used a visual analog scale; few studies used validated scales.

The 42 trials reviewed included 3,084 patients.

On the basis of limited data, NSAIDs appear to be more effective than placebo in treating cancer pain. Data to support the use of one NSAID over another, in regard to safety or efficacy, are insufficient. Compared to an NSAID alone or an opiod alone, NSAID-opioid combinations were no more effective or, at most, had a slight statistical advantage. The World Health Organization (WHO) method of cancer pain relief is considered the gold standard. Regarding the first step in the WHO method, the management of mild pain, results of this review support the WHO recommendations: Results strongly suggest that an NSAID alone is superior to placebo and adequate for at least short-term pain relief. Regarding the second step: Evidence is insufficient to refute or support the WHO recommendation to use an NSAID-opioid combination as a means to manage moderate cancer pain. Increasing the dose of an NSAID or adjuvant drug to the maximum acceptable dose may be the better course.

• Heterogeneity precluded meta-analysis.
• Short duration of studies undermines generalizability.
• Studies were too short to demonstrate the safety or efficacy of long-term NSAID use.

Clinicians should be cautious regarding the use of NSAIDs, especially in the population studied. This population takes many prescription drugs, some of which may increase NSAID-related toxicity.

To update evidence from randomized controlled trials (RCTs) regarding benefits of conservative and dietary interventions for all cancer-related lymphedema

Databases searched were MEDLINE, EMBASE, CINAHL, PubMed, Dissertation Abstracts, PEDro, and Cochrane Collaboration. Keywords were neoplasm, axillary dissection lymph node excision, lymphedema, conservative treatments (e.g., stockings compression, manual drainage), and publication types of random allocation and clinical trial. Studies were included in the review if they were RCTs with a sample of at least 80% patients with cancer comparing a conservative or dietary intervention to placebo, control, or comparison intervention in secondary lymphedema from cancer. Exclusion criteria were not specified.

Of the 157 papers that were initially retrieved, a final set of 25 were included. A modified Jadad scoring was used to evaluated the quality of the evidence. Only eight studies met criteria for high quality. Meta-analysis was done for studies examining the effect of manual lymph drainage (MLD)for upper-extremity lymphedema with breast cancer.

• The final sample of 25 papers involved 1,018 participants.
• Study sample sizes ranged from 11–90.
• Of the 25 papers, 21 were in patients with breast cancer.

Results were synthesized in terms of effects on lymphedema volume and patient-rated outcomes of pain, heaviness, tenderness and quality of life for nine interventions. Most studies were limited to upper extremities; where lower extremities were included is stated below.

• Strong evidence from three studies on exercise showed neutral impact on volume and benefit in symptoms and quality of life with upper extremities.
• There was moderate evidence from one study on compression bandaging for lower- and upper-extremity volume reduction and no evidence related to symptoms
• Compression Garments
• Moderate evidence found volume reduction for upper and lower extremities with compression garments. No evidence was found related to symptoms.
• Three studies had no evidence of benefit of MLD for symptoms; volume of lymphedema was not reported.
• One study showed moderate benefit related to short-term volume for deep mechanical oscillation with MLD and moderate evidence of benefit for symptoms in the short term but not at follow up.
• One study showed no evidence of any benefits from mechanically stimulated MLD.
• One study showed limited short-term benefit in lymphedema volume, but no evidence of benefit for symptoms with dietary modification.
• Four studies showed limited evidence of benefit in the short and long term for laser therapy ,and three showed limited evidence for benefit related to pain.
• One study provided no evidence of benefit from electrically-stimulated lymphatic drainage
• Four studies provided conflicting evidence, with two showing benefit in volume and two showing no benefit from intermittent pneumatic compression.
• Meta-analysis results found five studies including 198 cases examined the addition of MLD to compression therapy alone or compression therapy along with other interventions. 
• Analysis showed that the addition of MLD was beneficial (SD = 0.37, 95% CI 0.07–0.67, p = 0.02)

Meta-analysis demonstrated significant but relatively small benefit from the addition of MLS in patients with breast cancer-related lymphedema. Findings support the growing body of evidence that participation in exercise does not exacerbate lymphedema and can reduce the severity of symptoms. Only two studies were found that examined nutrition and dietary interventions; these reported benefit in terms of volume reduction, but were of relatively low quality. Evidence suggests that compression garments and bandaging are effective in reducing limb volume with various types of cancer.

Only eight studies in this review were deemed to be of high quality.

Inclusion of MLD provides a relatively small added benefit and may be associated with substantial costs. It is not clear if the benefits outweigh the cost and MLD may be most useful for patients who do not achieve sufficient improvement with other effective approaches. Findings related to dietary interventions are promising, pointing to the value of additional research in this area. Breast cancer continues to be the most frequently studied group. Research in other groups and with lower-limb lymphedema is needed.
 

To examine the evidence of effectiveness from randomized controlled trials involving exercise interventions for preventing, minimizing, and improving upper-limb dysfunction because of breast cancer treatment

Databases searched were Specialised Register of the Cochrane Breast Cancer Group, MEDLINE, EMBASE, CINAHL, and LILACS (to August 2008). Experts, hand-searched reference lists, conference proceedings, clinical practice guidelines and other unpublished literature sources were also considered. Search keywords were neoplasm, tumor, tumour, mastectomy, axillary dissection, sentinel node dissection, adhesive capsulitis, cording, axillary web syndrome, physical therapy, physiotherapy, rehabilitation, exercise, stretching, mobilization, physical activity, exertion, range of motion, strength, lymphedema, pain, and quality of life. Studies were included if they were randomized controlled trials evaluating the effectiveness and safety of exercise for upper-limb dysfunction. Studies were excluded if they included cancers other than breast cancer (e.g., melanoma) unless separate data were available for a breast cancer subgroup.
 

The total number of studies reviewed initially was 82. Two authors independently performed the data abstraction. One author performed the initial pre-screen of all the databases to identify potential trials and screened the results to exclude articles that were clearly irrelevant. Two independent authors screened the reduced search results. If either or both authors felt that the article potentially met the inclusion criteria, or if there was inadequate information to make a decision, full-text copies of the article were retrieved. Using the defined eligibility criteria, the two authors independently decided on trial inclusion. A priori, authors made the decision to exclude any data that were available only in abstract form. Review authors were not blinded to study authors, journal, or study results. Agreement was measured and assessed using kappa statistics. Three investigators independently assessed quality of the trials and extracted data independently using a standardized form. Investigators were contacted for missing data.
 

• The total number of studies included was 24.
• The sample size across studies was 2,132, with a range of 21–344.
• Patients were women with lymphedema after breast caner treatment.
• Mean age of patients ranged from 46.3–62.1 years.

Exercise can result in a significant and clinically meaningful improvement in shoulder ROM in women with breast cancer. There is evidence that patients benefit from exercise interventions that include more structured instruction and supervision when compared to exercise instruction through a pamphlet or no exercise instruction. Of note, larger benefits were found for shoulder range of motion and shoulder function outcomes from physical therapy treatment that was introduced in the early weeks following surgery. There was no evidence of a negative effect from upper-extremity exercise on the incidence of upper-limb lymphedema at any time point following surgery.

In the postoperative period, consideration should be given to early implementation of exercises, although this approach may need to be carefully weighed against the potential for increases in wound drainage volume and duration. High-quality research studies that closely monitor exercise prescription factors (e.g., intensity) and address persistent upper-limb dysfunction are needed.

To examine the effects of progressive resistance exercise training on upper extremity pain and dysfunction in postsurgical head and neck cancer survivors

Participants were randomly assigned to either standard therapeutic exercise or progressive resistance exercise training (PRET). All were asked to attend at least two supervised sessions per week for 12 weeks. Standard exercise involved active and passive range of motion and stretching, postural exercise, and strengthening with light weights (1–5 kg) and elastic resistance bands targeting specific muscle groups. The PRET group received the same exercises except that the strengthening was replaced with individualized exercise on the same muscle groups designed with the intent to provide progressive overload to those muscles. Outcomes were assessed at baseline and postintervention.

• The study reported on 52 head and neck cancer survivors.
• Mean participant age was 52 years (range = 32–76 years).
• The sample was 71% male and 29% female.
• To be eligible, participants had to have undergone surgical treatment, including radical neck dissection, modified radical neck dissection, or other variants of selective neck dissection; have a Karnofsky Performance Status score greater than 60%; have no evidence of residual cancer in the neck and no distant metastases; and have completed adjuvant treatment for head and neck cancer.
• All participants were required to present with symptoms of shoulder dysfunction attributed to spinal accessory nerve damage.

• Multisite
• Outpatient setting
• Cross Cancer Institute and University of Alberta in Edmonton, Canada

The study was a prospective randomized controlled trial.

• A block permutation procedure to generate the allocation sequence with each stratum Borg scale for rating of perceived exertion
• Training log
• Shoulder Pain and Disability Index (SPADI)
• Functional Assessment of Cancer Therapy–Anemia (FACT-An) scale for quality-of-life and fatigue assessment
• Neck Dissection Impairment Index (NDII)

The PRET program significantly reduced shoulder pain and disability (p = 0.001) and improved upper extremity muscular strength and endurance. Patients participating in the PRET program had a 52% reduction in pain. The effect size for change in pain was d = 0.84. PRET was better than the standard exercise for all strength endpoints measured, and endurance was more improved with PRET (p = 0.039).

Findings show that a program of individualized progressive resistance exercise in patients with specific shoulder dysfunction postsurgery for head and neck cancer as provided here can reduce pain and disability.

• Range of time from surgery varied widely among participants.
• Study results may have been limited by long-term survivors with deficits refractory to the exercise protocol that focused primarily on active and passive range-of-motion and basic strengthening exercises.
• The study did not differentiate between the location and type of pain in participants, nor did it differentiate involvement of the upper, middle, and lower trapezius, which may affect head and neck cancer survivors’ clinical presentation and response to treatment.

Survivors of head and neck cancer can be burdened with pain and loss of strength and function associated with damage to the spinal accessory nerve. It is important that nurses consider means that will help to minimize these residual effects. Exercise is a noninvasive tool that enables patients to actively participate in their recovery. This study shows that a PRET program had a beneficial effect, with reduction in pain of 52% in the PRET group. Improvement in pain was also associated with increases in upper extremity strength and endurance.