To determine the effectiveness of the probiotic Bifilact^® (Lactobacillus acidophilus LAC-361) on moderate and severe treatment-induced diarrhea in patients with pelvic cancer undergoing therapy, with a secondary objective to assess whether Bifilact^® decreased or delayed the need for antidiarrheal medication, reduced intestinal pain, decreased hospitalization, lowered the interruption of radiotherapy treatments or doses of both radiotherapy and chemotherapy, and improved the overall well-being of patients during treatment

Patients were divided into three groups: prostatic cancers, gynecologic cancers without chemotherapy, and gynecologic or rectal cancers with chemotherapy. Then, using double-blind procedures, patients were block-randomized by blocks of two, four, or six patients according to random permutations. A second random block using a higher probiotic dosage was added after an interim analysis. New, random lists were generated for each stratum with a 3:1:1 ratio (higher dose, standard dose, placebo). Nutritional intervention was enacted with a diet teaching to control dietary lipids and providing recommendations on fiber and carbohydrate intake. Yogurt consumption was encouraged.

• N = 246  
• MEAN AGE = Placebo 60.6 years; standard-dose 61.4 years; high-dose 62.0 years
• MALES: Placebo 63; standard-dose 72; high-dose 66, FEMALES: Placebo 37; standard-dose 28; high-dose 34
• KEY DISEASE CHARACTERISTICS: Prostate, endometrium, cervix, and rectum
• OTHER KEY SAMPLE CHARACTERISTICS: Surgery placebo 35%; standard-dose 39%; high-dose 30%; chemotherapy placebo 56%; standard-dose 54%; high-dose 45%

• SITE: Single-site    
• SETTING TYPE: Outpatient    
• LOCATION: L’Hôtel-Dieu de Québec University Health Center, Canada

• PHASE OF CARE: Active antitumor treatment

Prospective, single-center, placebo-controlled, randomized, double-blinded trial

• World Health Organization (WHO) scale of abdominal pain
• National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI, CTCAE) version 3.0 
• Fecal incontinence NCI scale version 3.0 stool consistency
• An adapted Bristol Stool Scale (BSS) was used to facilitate use by patients: grade 1 = normal stools (BSS 1–4); grade 2 = soft stools, in pieces (BSS 5–6), and grade 3 = liquid stools, no shape (BSS 7). 
• Patients undergoing chemotherapy received a weekly complete blood count. If a patient's neutrophil count was ≤ 1.5 x 10⁹/L, study agent was discontinued.
• A log book was kept for symptom documentation, stools, and medications such as antidiarrheals. 
• The European Organization for the Research and Treatment of Cancer's Quality of Life Questionairre C30 (EORTC, QLQ-C30) was completed at baseline, after radiation therapy was completed, and two weeks later.

229 patients were analyzed. For the primary endpoint among all groups, there was no difference in the effectiveness of the probiotic Bifilact^® (Lactobacillus acidophilus LAC-361) on moderate and severe treatment-induced diarrhea. At the 60-day point, there were more patients without moderate and severe diarrhea in the standard-dose group (35%) compared with the placebo group (17%) (hazard ratio of 0.69, p = 0.04). The postsurgical group with patients taking the standard dose had fewer patients without very severe diarrhea compared to the placebo group (97% and 74%, respectively) (p = 0.03). While undergoing therapy, the average number of bowel movements per day during treatment was less than three soft stools (p = 0.80), and the median level of abdominal pain was < 1 based on the NCI scale (p = 0.23).

Bifilact^®, when administered in standard doses to patients with pelvic cancer undergoing therapy, may reduce the risk of radiation-induced grades 2–4 diarrhea towards the end of the treatment. While receiving radiation therapy, a standard dose of probiotics may reduce radiation-induced grade 4 diarrhea in patients who had prior surgery.

• Key sample group differences that could influence results

Nurses may want to consider offering counseling and education regarding probiotics as a potential alternative approach to reducing radiation-induced diarrhea.

To review current evidence regarding the use of bisphosphonates for the treatment of lung cancer and to provide European recommendations for practice

An expert panel of European clinical oncologists and lung cancer specialists reviewed available evidence regarding the use of bisphosphonates for the treatment of lung cancer and developed recommendations based on the evidence and clinical experience. The International Association for the Study of Lung Cancer published the resulting report. Authors did not provide specific search description, cite the process of review, or present evidence.

The report made the recommendations that follow.

• Initial staging of lung cancer should include assessment for bone metastases.
• In caring for patients with lung cancer with bone involvement, clinicians must consider bisphosphonate as a treatment. Such treatment will delay and prevent further bone metastases, help prevent skeleton-related events, and relieve pain.
• Clinicians should add bisphosphonates to the treatment of those who develop bone metastases.
• Comprehensive dental examination should precede treatment with bisphosphonates.
• Treatment with bisphosphonates should continue as long as feasible, in the absence of severe adverse effects.
• Bisphosphonate treatment, in combination with chemotherapy, is generally well tolerated and may produce synergistic effects.
• Zoledronic acid is recommended for the treatment of patients with lung cancer and bone metastases.

The International Association for the Study of Lung Cancer recommends the use of bisphosphonates in general and zoledronic acid in particular for patients, with all types of lung cancer, who have bone metastases. Nurses should be aware of potential adverse events of this treatment, though it is generally well tolerated. Because bisphosphonate treatment is associated with osteonecrosis, patients should have a comprehensive dental examination and prophylaxis before starting bisphosphonate treatment. Nurses should also be aware of the potential renal effects of bisphosphonate, especially on patients whose renal function has deteriorated as the result of other nephrotoxic drugs, dehydration, renal impairment, or lack of adherence to the recommended infusion schedule for bisphosphonate.

To examine the effect of probiotic use for prevention of radiation-induced diarrhea

The experimental group received high-potency probiotics (VSL#3 in one sachet) three times per day beginning on the first day of radiation therapy until the end of scheduled cycles. The VSL #3 sachet contained 450 billions/gm of viable lyophilized bacteria, including 4 strains of lactobacilli (Lactobacilli casei, L. plantarum, L acidophilus, and L. delbruekii subsp. Bulgaricus); 3 strains of Bifidobacteria (B. longum, B. breve, and B. infantis) and 1 strain of Streptococcus salivarius subsp. thermophilus.

The control group received an identical-appearing placebo.

This study reported on 490 patients receiving adjuvant radiation therapy after surgery for sigmoid, rectal, or cervical cancer.

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

Efficacy endpoints included incidence and severity of radiation-induced diarrhea, the number of bowel movements (BMs) per day, and the time from start of study until need for loperamide.

Endpoints (clinical symptoms, use of medications, and any adverse events) were reviewed with patients weekly during scheduled radiation therapy treatments and again one month after completion.

• In all, 97.5% of patients in the placebo group and 99.1% of patients in the experimental group completed study.
• More patients in the placebo group had radiation-induced enteritis and colitis (p < 0.001).
• The placebo group experienced more severe toxicity (grade 3 or 4) (p < 0.001) and had a higher mean daily number of BMs (p < 0.001).

Use of a probiotic lactic-acid producing bacteria is a safe, easy, feasible approach to preventing radiation-induced diarrhea after surgery for abdominal and pelvic cancer.

• Severity was assessed using World Health Organization (WHO) standards whereas other studies use National Cancer Institute (NCI) standards.
• This study looked only looked at prevention of radiation-induced diarrhea. 
• The study did not address safety in patients who are neutropenic.

Probiotic lactic-acid-producing bacteria is safe for use in patients receiving radiation treatment, and it is not associated with bacteremia, sepsis, or septic shock. Lactobacilli lowers the production of proinflammatory cytokines and other effectors of inflammation and tissue injury. Probiotic bacteria upregulates the innate immune response in the gut and protects against invasive organisms. Further studies are needed on different probiotic preparations and mixtures.

To compare melatonin with placebo for impact on appetite in patients with advanced cancer

Patients were randomly assigned to receive 20 mg melatonin or identical placebo daily for 28 days. Study assessments were done at baseline and at four weeks. Patients were stratified according to whether or not they were currently receiving antitumor treatment.

• The study reported on a sample of 48 patients.
• Mean patient age was 60 years, with a range of 32–86 years.
• The sample was 56% female and 44% male.
• All patients had locally recurrent or metastatic disease.

• Multisite
• Outpatient setting
• Texas

 The study was a double-blind, randomized, placebo-controlled trial.

• Edmonton Symptom Assessment Scale
• Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F)
• FACIT subscale questionnaire
• Toxicity questionnaire
• Bioimpedance for body composition and weight
   

There were no significant differences between groups in symptoms or change in symptoms at four weeks. There were no differences in change in body weight or body composition. Thirty-three percent of patients were lost to follow-up.

Melatonin had no effect on appetite or other symptoms in patients with advanced cancer.

• The study had a small sample size, with less than 100 patients.
• Patient withdrawals were 10% or greater.

Findings of this study do not support the use of melatonin to improve appetite or other symptoms in patients with advanced cancer.

To evaluate the effect of dry extract guarana (PC-18) on cancer-related fatigue (CRF) in patients with solid tumors and to evaluate the effect of maintenance doses on CRF in patients who initially improve

PC-18 37.5 mg orally twice daily for 21 days. Those with improved or stable BFI scores were randomized to 37.5 mg BID dosing of PC-18 or placebo for an additional 21 days.

• N = 40 in the induction phase and 33 in the randomization phase
• MEAN AGE = 55.9 years in the induction phase, 52.17 years in the placebo group, and 58 years in the PC-18 group
• MALES: 42.5% induction, 39.4% randomization; FEMALES: 57.5% induction, 60.6% randomization
• KEY DISEASE CHARACTERISTICS: Breast: 25% induction, 30.3% randomization; colorectal: 22.5% induction, 21.2% randomization; lung: 10% induction, 9% randomization; head and neck: 12.5% induction, 9% randomization; other: 30% induction, 30% randomization.
• OTHER KEY SAMPLE CHARACTERISTICS: Cisplatin-based chemotherapy: 25% induction, 24% randomization; doxorubicin-based: 17.5% induction, 15% randomization. All participants receiving FLOX/Xelox/FOLFOX received PC-18 after randomization (15% of randomized participants). All receiving Folfiri also received placebo after randomization (15% of randomized participants).

• SITE: Multi-site  
• SETTING TYPE: Not specified  
• LOCATION: Sao Paulo, Brazil

• PHASE OF CARE: Active anti-tumor treatment

• Stage I, uncontrolled, open study
• Patient showing improvement or stabilized BFI scores were then randomized to continue study drug or placebo.

• Brief Fatigue Inventory
• FACIT-F
• Chalder
• HADS
• PSQI

Mean BFI score decreased by 2.503 points (p = .0002). No significant difference was noted between PC-18 and placebo groups after randomization in BFI (p = .8499), Chalder (p = .6321), FACIT-F (p = .7452), HADS-A (p = .7521), HADS-D (p = .9425), or PSQI (p = .807). There was one instance of grade III depression and one instance of grade III dizziness experienced in PC-18 that was not experienced in placebo. Grade II dizziness and tremors (one instance of each) also reported in PC-18 group, but not in placebo group.

BFI improvement was seen in the induction phase with no significant difference once patients were randomized. It is difficult to make any positive conclusions on guarana as all patients initially had the drug with no washout period before randomization. Potential side effects of guarana may be undesirable.

• Small sample (< 100)
• Risk of bias (no control group)

The study is limited by its sample size and study design. Use of guarana for CRF is not supported by this study.

Gluteal injections of testosterone or placebo were administered at baseline, day 15, day 29, day 43, and day 57. Outcome measures were determined on day 29.

• N = 29
• MEAN AGE: 63 years for placebo group and 57 years for testosterone group
• MALES: 100%
• KEY DISEASE CHARACTERISTICS: Outpatient males with advanced cancer, bioavailable testosterone (BT) < 70 ng/dL, and fatigue scores > 3/10 on Edmonton Symptom Assessment Scale

• SITE: Multi-site  
• SETTING TYPE: Outpatient  
• LOCATION: Texas VA Hospital and University Cancer Center

PHASE OF CARE: Transition phase after active treatment

APPLICATIONS: Elder care and palliative care

Randomized, double-blinded placebo-controlled trial

• Eastern Cooperative Oncology Group (ECOG) Performance Status
• Edmonton Symptom Assessment Scale (ESAS)
• Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F)
• Functional Assessment of Anorexia/Cachexia Therapy (FAACT)
• Hospital Anxiety and Depression questionnaire (HADS)
• Sexual Desire Inventory (SDI-2)
• International Prostatic Symptom Score (IPSS)
• Body composition by bioimpedence
• Six-minute walk
• Get-Up-and-Go test
• Handgrip strength
• Bioavailable testosterone

There were no statistically significant differences in FACIT-fatigue subscale or total scores; in testosterone levels between placebo and testosterone groups; and in the secondary outcome of anorexia/cachexia and sexual desire at day 29. ECOG-PS scores improved in the testosterone group, but the differences were not significant.

Testosterone replacements in hypogonadal male patients with advanced cancer did not significantly improve quality of life.

• Small sample (< 30)
• Key sample group differences that could influence results
• Measurement validity/reliability questionable
• Findings not generalizable
• Other limitations/explanation: Confounding variable of anemia; questionable use of bioimpedance as a measure of body composition; limited accrual; and limited length of intervention (4 weeks)

This study did not demonstrate any benefit of testosterone replacement in this group of patients.

Patients were treated with 350 mg/m² irinotecan during their first cycle of chemotherapy combined with 660 mg neomycin (n = 28; 45%) administered three times daily for three consecutive days starting two days before irinotecan or combined with placebo (n = 34; 55%). 

The two groups were balanced for demographic parameters, hematologic function, bilirubin, and liver enzyme values. The administered dose of irinotecan did not differ significantly between groups (mean dose of 640 mg versus 679 mg, p = 0.9).

This was a double-blind, randomized, placebo-controlled study.

• The National Cancer Institute (NCI) Common Toxicity Criteria (CTC), version 2, was used for diarrhea, nausea, and vomiting up to three weeks following administration of irinotecan. 
• Duration of diarrhea (in days) was scored.

• Overall incidence and severity of delayed-type diarrhea did not differ significantly between study groups (p = 0.33).
• The neomycin group experienced a 45% lower incidence of grade 3 diarrhea compared to the placebo group (17.9% versus 32.4%; p = 0.19). However, no difference was found between study groups when combining grade 2 and 3 incidence (46.4% versus 50.0%; p = 0.78).
• Treatment with neomycin did not result in significantly shorter duration of diarrhea (4.0 versus 4.9 days; p = 0.32).

• Patients receiving neomycin had a 4.5 times higher risk for grade 2 nausea than those receiving placebo (39.9% versus 8.8%; p < 0.01). 
• A larger trial is warranted.

To evaluate the effects of antiseptic drain care on drain colonization and infection after immediate breast reconstruction

Patients undergoing bilateral mastectomy and immediate breast reconstruction had right and left breast area randomly assigned to usual drain care or the experimental protocol. All subjects received IV antibiotics within 30 minutes of surgical incision and oral antibiotics until drains were removed. All participants and family members were instructed in drain care. The experimental procedure involved application of a chlorhexidine disc to drain sites every three days and irrigation of the drainage bulb with dilute Dakins solution (0.0125% sodium hypochlorite) twice daily. Patients were followed at post-op day (POD) 6–10 for culture of drain fluid. Drains were removed as individually appropriate, and tubing and fluid were cultured at that time. Surgical site infections were identified within 365 days of surgery.

• N = 104 patients, 208 individual surgical sites  
• MEDIAN AGE = 46 years
• AGE RANGE = 25–87
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Patients had either breast cancer or bilateral mastectomy for cancer prevention. Over 50% had a mastectomy for risk reduction.

• SITE: Single site  
• SETTING TYPE: Multiple settings
• LOCATION: Rochester, NY

• PHASE OF CARE: Active antitumor treatment

• Single blind randomized, controlled parallel group trial

• Drain and tubing colonization defined as ≥ 50 colony-forming units
• Surgical site infection (SSI) defined as purulent drainage, positive culture from the wound, inflammation with incision opening without positive culture, or physician diagnosis of infection. SSI was determined by team consensus, who were blinded to the study group.

Drain bulb fluid colonization POD 6–10 was 9.9% with antisepsis and 20.8% with control management (p = 0.02). Drain tubing and bulb fluid colonization at removal was significantly higher in the control condition (p ≤ 0.03). At POD 30, SSI rate was 3.8% among controls and 0% with the antisepsis protocol, and at one year, SSI rate was also lower in the antisepsis group. SSI rates were not significantly different.

Drain antisepsis with chlorhexidine patch and irrigation with dilute Dakin’s solution was associated with reduced drain and drain fluid colonization, but did not produce significant differences in surgical-site infections.

• Questionable protocol fidelity
• Care was done by patients in the home, and adherence to protocol was unclear. Usual care was not described.

The procedure tested here for drain antisepsis produced less drain colonization but did not demonstrate longer term significant results to reduce surgical site infection, though infection rates were lower with the antisepsis. Further research is warranted to confirm any significant difference. Though SSI rates tend to be rather small, SSI post bilateral mastectomy and breast reconstruction can be devastating. Drain antisepsis approaches may provide an opportunity to reduce risk of postoperative surgical-site infections in which drains are used.

To identify guidelines for implementing intrathecal therapy (IT) and provide considerations for effective analgesia for chronic pain in patients with cancer or others at the end of life

• Authors state that the guidelines are based on available evidence from observational and randomized, prospective trials.
• Databases searched were not reported.
• Search keywords were intrathecal, cancer, palliative, pain, guidelines, opioids, consensus, selection, and evidence.
• Studies were included in the review if they involved patients with cancer-related pain or other end-of-life states causing pain.
• Exclusion criteria were not included.
• No conflicts of interest were identified.

This resource provides a summary of evidence and relevant recommendations regarding patient selection for IT therapy, implications of prior therapy and its results, use of IT pain therapy with concurrent chemotherapy or radiation, implications with epidural metastases, infection, comorbid conditions, social issues, and healthcare coverage.

• Several trials have demonstrated that IT therapy can reduce neuropathic-nociceptive pain while reducing drug-related toxicities and the need for supplementary systemic opioids.
• Despite a lack of robust evidence, clinical experience suggests that patients with poor pain relief or intolerance with systemic opioids can be effectively managed with IT.
• Potential clinical side effects include hyperalgesia, hypotension, sedation, and respiratory depression. Proper monitoring is essential, particularly in the first 24 hours after drug initiation.
• Patient selection should be based on the type of pain, although limited evidence exists in this area. IT may be appropriate for patients with soft tissue cancers with visceral nociceptive pain and pain attributed to bone metastases.
• No confirmed association has been found between patient response to oral opioids and response to IT therapy.
• Systemic infection was identified as a contraindication to device implantation. The authors reviewed evidence from the Centers for Disease Control regarding prophylaxis for surgical site infection. IT has been found to be useful for patients who are immunocompromised.
• Battery drain or electric failure of the implanted device can occur if the pump is directly in the radiation field and shielding. Minimizing radiation exposure or relocating the pump should be considered if the pump is directly in the radiation field.
• IT requires appropriate social support for follow-up and ongoing care. Lack of insurance coverage or social support is a contraindication to device implantation.

Recommendations provided are limited by reliance on consensus and the limited evidence available from clinical trials regarding the application of IT.

Consideration for comorbidities, support systems, compliance with recommended treatment plan, current or prior therapies, incorporation of the oncologist into the treatment plan, psychological monitoring, and appropriate trialing technique are key in the use of IT therapy. The authors advocate for wider application of IT therapy to effectively manage patients experiencing cancer and end-of-life pain.

To assess the effect and tolerability of oral normal-release morphine (NRM) during the initial phase of the treatment of patients with moderate to severe cancer pain

Eligible patients received oral NRM at a starting dose of 5 or 10 mg every four hours. Patients whose pain was not controlled with World Health Organization (WHO) step I analgesics received 5 mg NRM. Patients who received step II therapy received 10 mg NRM. Patients who did not get satisfactory pain relief during the interval between one dose and the next could take rescue doses of oral NRM, up to one dose every hour; rescue NRM doses were the same as the patient’s regular doses. Dose was retitrated on a daily basis so that the dose of oral NRM to be given in the next 24 hours was based on the total opioid dose (regular plus rescue). If possible, patients completed an ambulatory visit for assessment after two and five days from the beginning of the study. On other days, patients received a telephone call that monitored pain intensity, drug dose, and onset of symptoms.

• The sample was composed of 159 patients; 135 completed the study.
• Mean patient age was 65 years. Age range was 29–87 years.
• Of all patients, 34.6% were female and 65.4% were male.
• All patients had advanced cancer. The sample included multiple diagnoses. The pain score of all patients was 5 or higher for at least 24 hours.

• Multisite
• Outpatient
• Sixteen palliative care centers in Italy

Open-label, phase IV clinical trial

• Numeric Rating Scale (NRS) for pain (0 = no pain, 10 = worst pain possible), as reported in each patient's diary
• Mini Mental State Examination (MMSE) (The number of potential subjects who were excluded was fewer than six.)
• Karnofsky Performance Status Score, as reported in each patient's diary
• NRS regarding morphine dosage and adjunct analgesic therapy
• NRM-related adverse events, presence and frequency of episodic pain
• Score on intensity scale, 1–3 (1 = mild, 2 = moderate, 3 = severe), as assigned during physician assessment at visits, to assess safety of NRM

• Of patients categorized as “intent to treat,” or ITT, a very high percentage (45%) achieved pain control for more than 90% of the follow-up period. Of these patients, 79% achieved pain control within 24 hours after taking the first oral NRM dose; 50% of these patients achieved pain control within the first eight hours.
• Most commonly reported adverse events were somnolence (24% of patients), constipation (22%), vomiting (13%), nausea (10%), and confusion (7%). These events occurred primarily in the first days of treatment. With the exception of constipation, none of the events required treatment. Authors observed no unexpected adverse events.

Oral NRM, administered according to European Association for Palliative Care recommendations, can effectively and rapidly decrease pain intensity. In opioid-naive patients, oral NRM has an acceptable safety profile.

• The study had a risk of bias due to no appropriate control group.
• The study was conducted in 16 palliative care units in Italy. Future researchers should repeat the study in a more general setting and in other countries.

This trial demonstrated that clinicians should begin administering NRM as soon as possible to treatment moderate to severe cancer-related pain instead of waiting until the patient is at an advanced or terminal stage. Through titration, the analgesic treatment was tailored to the patient’s needs, and close evaluation and re-evaluation of pain intensity and frequency helped ensure that the therapy continued to be effective and tolerated. Nurses can advocate for NRM when caring for patients with higher levels of pain, thereby increasing the patient’s level of comfort and optimizing patient-centered treatment.