To test whether oral alpha-lipoic acid (ALA) could reduce the severity of peripheral neuropathy in patients receiving platinum-based chemotherapy

Prior to randomization, patients were stratified according to prior exposure to platinum-based therapy dosages. Patients were assigned to receive ALA 600 mg oral sustained-release tablets three times per day. Control patients received a matching placebo. Medications were taken continuously for 24 weeks between two days prior and four days after each dose of platinum.

• N = 70   
• MEAN AGE = 56 years
• MALES: 53%, FEMALES: 47%
• KEY DISEASE CHARACTERISTICS: Gastrointestinal cancers were most common. Dosage of platinum compounds were in excess of 750 mg/m²​.
• OTHER KEY SAMPLE CHARACTERISTICS: Patients with neuropathy and diabetes mellitus, and those exposed to carboplatin, vincristine, paclitaxel, or docetaxel within the past six months were excluded.

• SITE: Multi-site   
• SETTING TYPE: Outpatient   
• LOCATION: Texas

• PHASE OF CARE: Active antitumor treatment

• Double-blind, placebo-controlled RCT

• FACT/GOG-NTX (version 4) for neuropathic symptoms
• Brief Pain Inventory
• Functional tests—time to button a six-button shirt, 50-foot walk, and coin test

Only 28% in the ALA arm and 30% in the placebo arm completed 24 weeks of the study. Most discontinued the study because of withdrawal of consent and noncompliance. Neuropathy scores increased significantly from baseline in both groups at 24 weeks (p < .001). No differences were observed in study results between groups.  Authors state that attrition was not related to toxicities and that adverse events were comparable between groups.

Findings did not show a beneficial effect of ALA for prevention or reduction of peripheral neuropathy in patients receiving platinum-based chemotherapy.

• Small sample (less than 100)
• Subject withdrawals 10% or greater
• Other limitations/explanation: Extensive attrition, suggesting that the intervention was not acceptable to patients

Findings do not show a benefit of oral ALA for prevention of chemotherapy-induced peripheral neuropathy with platinum-based chemotherapy. Management and prevention of chemotherapy-induced peripheral neuropathy is a challenge that is generally managed by dose reduction or chemotherapy discontinuation, which can reduce effectiveness in treatment of cancer. Few approaches have shown to be effective in preventing or reducing chemotherapy-induced peripheral neuropathy. Ongoing research in this area is needed.

To evaluate the safety and efficacy of transdermal fentanyl for oral mucositis pain

Transdermal fentanyl was given at a rate of 25 mcg per hour to patients with pain scores greater than five during treatment and increased by 25 mcg per hour to maintain pain scores less than or equal to three on a numeric rating scale. Study assessments were done on days 1, 4, 7, and 10. Patients rated pain daily.

• N = 78
• MEDIAN AGE = 41 years (range = 31–52 years)
• MALES: 75.6%, FEMALES: 24.4%
• KEY DISEASE CHARACTERISTICS: All participants had nasopharyngeal cancer and were receiving daily radiation therapy of prescribed doses of 70 Gy to the planning target volume. Patients also were receiving chemotherapy of cisplatin with 5-FU or taxol and cisplatin.

• SITE: Single-site
• SETTING TYPE: Outpatient
• LOCATION: China

PHASE OF CARE: Active antitumor treatment

Open-label, observational trial

• Pain numeric rating scale
• Score for pain, Physical activity levels, Additional pain medication, Additional physician/emergency room visits, Sleep, Mood, and Side effects (SPAASMS)

Mean pain scores declined from 7.41 before treatment to 5.54 (SD = 0.86, p < 0.001) on day 1 and 2.82 (SD = 0.68, p < 0.001) on day 10. Sleep quality was improved after treatment (p < 0.001). The most frequent side effect was nausea and vomiting. No patients discontinued treatment.

Transdermal fentanyl was quickly effective in reducing pain from oral mucositis in this patient population. Pain reduction was associated with improved sleep.

• 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
• Other limitations/explanation: The method of sleep quality measurement was not described. The final doses of fentanyl were not reported.

The findings of this study demonstrated that transdermal fentanyl was effective in reducing oral mucositis-related pain within one day, and pain scores continued to decline during combined radiation and chemotherapy. They also suggested that adequate pain control in this patient population improves sleep quality and other aspects of quality of life.

Many patients with cancer experience depression and anxiety, with an associated decrease in quality of life, during radiation therapy. The main objective of the study was to determine the benefits of psychosocial interventions for these patients with cancer, concurrent with radiation therapy.

Patients in the intervention group received psychosocial care, which consisted of psychoeducation, cognitive behavioral therapy (CBT), and supportive expressive therapy.

• N = 178
• MEAN AGE = 47 years
• MALES: 42%, FEMALES: 58%
• KEY DISEASE CHARACTERISTICS: Patients with cancer undergoing radiation therapy
• OTHER KEY SAMPLE CHARACTERISTICS: 96% of patients had Eastern Cooperative Oncology Group performance status of 1–2, meaning that they were fairly fit. Radiation therapy had to be given with curative intent, not palliative.

• SITE: Not stated/unknown  
• SETTING TYPE: Outpatient  
• LOCATION: Guilin Medical University, Guangxi Province, China

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

Patients were randomized to the intervention arm (psychoeducation, CBT, and supportive expressive therapy) or to the control arm. The control group received radiation therapy only.

• Zung Self-Rating Depression Scale for symptoms of depression
• Self-Rating Anxiety Scale
• European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30.  

An association also was made between intervention and survival.

Patients in the intervention group showed significant improvements in symptoms of depression and anxiety and health-related quality of life. They had better global health status and physical and emotional functioning and less insomnia. No difference was observed between groups in disease-free survival and overall survival.

Psychosocial interventions appear to be a cost-effective approach that can improve a patient’s mood and quality of life during and after radiation therapy.

Chinese study (possible cultural implications)

This is an important study for oncology nurses, especially radiation therapy oncology nurses, who often feel like they cannot make much impact on their patients' lives, except for checking for toxicities. Nurses have an important role in psychoeducational and supportive therapies. Some very brief strategies being taught regarding CBT and supportive expressive therapy could go a long way in helping many patients.

To assess the effectiveness of prophylactic antibiotics on prevention of surgical site infection (SSI) and the cost of this effectiveness, as compared to a control without prophylaxis antibiotics in early breast cancer surgery in overweight or obese women

Women randomly were assigned to receive IV infusion of 1 g ampicillin-sulbactam at the start of anesthesia or no prophylactic antibiotics. Patients were followed for 30 days. Outcomes also were compared to a group of women who had a body mass index (BMI) lower than 25 and who did not receive antibiotic prophylaxis.

• N = 369 (187 in the prophylaxis group, 182 in the control group)
• AGE = 58 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: BMI of 25 or higher; all had nonrecurrent, operable breast cancer

• SITE: Single site 
• SETTING TYPE: Inpatient 
• LOCATION: Tertiary university hospital in Turkey

• PHASE OF CARE: Multiple phases of care

• Phase IV, randomized, controlled, parallel-group

• SSI was defined as infection within 30 days post-operation with one of the following.
  • Purulent drainage from incision
  • Organisms isolated from incision cultures
  • Localized pain
  • Tenderness
  • Swelling
  • Redness of an incision deliberately opened by the surgeon
• ASA class

Nine SSIs developed in the prophylaxis group, versus 25 in the control group (p = .002). Patients were matched well according to age, BMI, history of smoking, ASA class, interval between tissue biopsy and randomization, clinical cancer stage, type of breast and axillary surgery, operation time, hospital stay, and post-operation complications. All SSIs were discovered within post-operation week one after discharge, except one. The control group had significantly more SSIs compared to those in the normal-weight comparison group (p = .0007) and higher SSI treatment costs than the prophylaxis group (p = .007). Patients in the control group had more open surgical biopsies than those in the prophylaxis group (p = .004)

The administration of antibiotics at the time of induction for surgery was associated with reduced incidence of SSI among obese women undergoing breast cancer surgery. Costs were lower among those receiving prophylactic antibiotics.

• Risk of bias (no blinding)
• Risk of bias(sample characteristics)
• Other limitations/explanation: The control group underwent more biopsies prior to surgery; mastectomy is more common in Turkish culture.

Reminding physicians to prescribe pre-operation antibiotics is important. Administration of a dose of IV antibiotics at the time of induction is a current U.S. standard of care and recommendation for SSI prevention. Careful hand washing and clean dressing changes are imperative. These findings also point to the increased risk of infection associated with obesity. Nurses can educate patients regarding risks associated with obesity and assist patients with weight management.

To determine the effect of oral proteolytic enzymes for prevention of acute side effects in patients with head and neck cancer.

Patients were randomly assigned to the control or experimental group.

The enzymes taken were a combination of papain 100 mg, trypsin 40 mg, and chymotrypsin 40 mg (MUCOS Pharma). Patients took three tablets, three times per day, three days prior to start of radiation therapy (RT), and up to five days after completion.

Mucositis, skin reaction, and dysphagia were graded at each visit during and after RT. Scoring was done at baseline, weekly, and five to six months following treatment.

• The sample was comprised of 98 men.
• Age ranged from 18 to 65 years.
• Patients had T3/T4 cancers of the head and neck region with squamous cell.
• Patients received Cobalt 60 gamma radiation at a standard daily dose of 2 Gy in 25 to 35 fractions over six to seven weeks. 
• Thirty-three patients were hospitalized to ensure compliance.

• Multisite
• Indore and Cuttack, India

The study was a prospective, randomized, open-label trial.

• Radiation Therapy Oncology Group (RTOG) criteria
• Compliance was monitored by counting pills.
• Grading was performed by the same person every time.
• Wilcoxon summed was used to test for differences.

• The average skin reaction score was lower in those treated with enzymes (p < 0.0001).
• The maximal extent of acute toxicity was lower in those who took enzymes.
• Two patients in the experimental group were dropped due to the most severe acute reactions.

Oral proteolytic enzymes may be helpful in reducing the severity of radiodermatitis.

• Slightly more than one-third of the patients had to be hospitalized to ensure compliance with treatment, which suggests the impracticality for clinical use in this population.
• Multiple patients had treatment delays, most of which were associated with social issues.
• Skin reactions per RT dose levels were not compared.

To determine the effectiveness of an assistive mobile flexion bar during exercise to reduce arm volume in patients diagnosed with lymphedema related to breast cancer treatment

Participants were randomly selected, and all participants received the intervention. Participants received a single one hour of active exercising split into 12-minute sections with 3 minutes of flexion bar use between each section. The flexion bar is a T-shaped apparatus, the vertical bar remains fixed (10 cm away from the patient on a tabletop), and the horizontal bar rotates (30 cm above the tabletop) to allow extension and flexion of arm muscles. All of the participants wore a compression sleeve on the affected limb. The participants independently performed the exercise routine, and the sole purpose of the interventionist was to control the time of exercise intervals and to help participants maintain proper posture and spinal alignment.

• The study sample (N = 21) was comprised of female patients with breast cancer who were diagnosed with arm lymphedema.
• All patients had radiotherapy postoperatively and were 2–12 years postoperative.

The study took place at a rehabilitation facility in Brazil.

Patients were undergoing active lymphedema treatment.

The study used a prospective trial design.

• Water displacement measured limb volume before and after the flexion bar intervention.
• Participants' arm volume was measured before and after each exercise session.

The participants initial mean volume was 2,089.9 ml. After the exercise session, the mean final volume decreased to 2,023.0 ml. The study used a paired t-test with an alpha error of 5% as acceptable. The results concluded in a mean loss of 66.9 ml (p < 0.001). There was a significant reduction in limb volume, using active exercises with a facilitating device (mobile flexion bar).

The trial suggests that the use of an apparatus mobile flexion bar may improve the efficacy of lymphedema reduction by myolymphokinetic exercises. Active exercises are beneficial to patients with lymphedema because it promotes muscle contraction and lymphatic drainage. The study has its risks for bias based on the small sample size and the lack of a control group.

• The sample size was small, with less than 30 participants.
• The time in years from surgery is a large range.
• The study has a risk of bias because of no control group, blinding, or random assignment.

Because of the statistical significance of the findings of the study, it is important for nurse researchers to repeat the study using a more rigorous study design. If the experiment were repeated as a randomized controlled trial with a larger sample size, the results would be more generalizable. It would also be interesting to compare the use of a mobile flexion bar to active exercise without the use of a facilitating device to determine the necessity.

STUDY PURPOSE: To investigate the efficacy of antidepressants and anticonvulsants in combination therapy for neuropathic pain in patients with cancer

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 8
• TOTAL PATIENTS INCLUDED IN REVIEW: 1,359
• SAMPLE RANGE ACROSS STUDIES: Unavailable
• KEY SAMPLE CHARACTERISTICS: Five studies involved chemotherapy-induced neuropathic pain, and one involved postmastectomy pain. One study included only breast cancer. Four studies included varied tumor types.

PHASE OF CARE: Multiple phases of care
 
APPLICATIONS: Palliative care

When both types of interventions were considered, use of these adjuvant medications in combination pharmacotherapy was superior to control regimens (p < 0.010, MD = -0.41). However, in subgroup analysis, anticonvulsants (MD = -0.12, 95% CI [-0.64, 0.39]) did not show a significant effect. Antidepressants showed some efficacy (MD = -0.54, 95% CI [-0.94, -0.12]) based on only two studies. Anticonvulsants showed better efficacy among studies including only chemotherapy-induced neuropathic pain. Withdrawals in experimental groups was two times higher than in control groups. Study duration ranged from 10 days to 6 weeks.

Use of adjuvant antidepressants and anticonvulsants had a significant but small effect on neuropathic pain, and anticonvulsants considered alone showed no overall significant effectiveness. Evidence was too limited to formulate a recommendation for use.

• Limited number of studies were included.
• Few studies existed for each type of medication.
• Three studies were of very short duration.
• Overall analysis included a study with topical application and one that included opioid use in the experimental group—these inclusions could have skewed overall findings.

There is limited evidence to demonstrate effectiveness of anticonvulsants or antidepressants as adjuvant medications for neuropathic pain management, and high withdrawal rates in studies within groups receiving these drugs may point to their potential side effects. Nurses need to be aware of and monitor the adverse side effects of these medications.

To examine the effect of colony-stimulating factors (CSFs) used as primary and secondary prophylaxis on incidence of febrile neutropenia, infection, and survival in older adults.

The study used data from the Surveillance, Epidemiology, and End Results (SEER) Medicare database. ICD-9 codes were used to define inclusion diagnoses and definition of febrile neutropenia. 

Use of CSF, the type of chemotherapy administered, and the use of antibiotics were defined in terms of CPT codes. Regression analysis was used to analyze effects of primary and secondary CSF prophylaxis on outcomes of interest. Primary prophylaxis was defined as CSF during chemotherapy before occurrence of fever, infection, or neutropenia. Secondary prophylaxis was CSF administration that occurred after these events. Study used data from 1992–2002.

• Total cases numbered 13,203, with 5,266 receiving any CSF.
• Mean age was 74.9 years, with a range of 65–102.
• Women made up 53% of the sample; men made up 47%.
• All patients had non-Hodgkin lymphoma (NHL). 
• 62% had low comorbidity burden, as defined by ICD-9 coding.
• 44% had large B-cell lymphoma.
• 18% had follicular lymphoma. 
• 89.2% were Caucasian. 
• All socioeconomic groups were essentially equally represented.
   

Multi-site (SEER data)

There were mutliple phases of care

Application is for elder care

Retrospective cohort study

• Chemotherapy administration defined as ICD-9 code 9925; CPT codes 96400-96549, J9000-9999, and Q0083-0085; revenue codes 0331, 0332, and 0335; and ICD-9 V codes, k V58.1, V66.2, and V67.2.
• Use of CSF was identified by CPT codes J1440, J1441, and J2820.
• Febrile neutropenia was defined as the combination of neutropenia (ICD-9 288.0) and fever present (780.6).

Sixty percent of cases did not receive any CSF. Those who had 5–9 CSF administrations for primary prophylaxis has a 42% lower risk of febrile neutropenia (OR = 0.58, 95% confidence interval [CI] [0.41, 0.83]) and those with 10 or more administrations had a 48% lower risk after data were adjusted for age, marital status, stage, and other characteristics. Those with 5–9 administrations had a 27% lower incidence of infection, and those with 10 or more administrations had a 52% lower risk (OR = 0.48, 95% CI [0.35, 0.66]). Primary prophylactic CSF was not associated with longer overall survival. Secondary prophylaxis was associated with improved overall survival, with a strong dose-response effect. A range of 11–23 administrations was associated with a 23% lower risk of mortality (HR = 0.77, 95% CI [0.71, 0.84]), and those with more than 23 administrations had a 13% lower risk of mortality than others. Protective effects of primary prophylaxis was highest in those receiving the largest number of chemotherapy administrations and in those with large B-cell lymphoma.

Primary prophylaxis with CSF in older adults is effective in preventing febrile neutropenia and infection, but was not associated with improved survival. Secondary prophylaxis was associated with longer overall survival.

• Risk of bias (sample characteristics)
• Measurement validity/reliability questionable
• Findings not generalizable
• Measurement validity/reliability questionable
• The sample was limited to patients with NHL from 1992–2002, and findings would not necessarily be applicable to patients with other types of disease and those receiving newer and other treatment regimens. 
• Although data were stratified for classes of chemotherapeutic drugs there was no specific subgroup analysis based on different types of chemotherapy or other treatments.
• Reliability of medical records coding is across organizations is known to be questionable, so findings should be considered with this in mind.
• Definition of neutropenia by code, which depends upon physician documentation and does not specify actual lab results as criteria can be questionable.
• A higher proportion of patients who got primary prophylaxis had higher stage disease—it is not stated as to whether there were statistically significant differences in this factor or not and those who received CSF were more likely to have received radiation therapy as well.   
• Although data were said to be stratified for age, it is not clear if the factor of combined therapy was considered in analysis.

Findings support the use of primary prophylactic CSF for prevention of infection and febrile neutropenia, and secondary prophylaxis in improving survival in this group of patients. Limitation of retrospective statistical analysis using medical records code data only need to be considered in interpretation and application of these results.

To provide advice for patient care in daily practice regarding the management of side effects of sunitinib.

Information was compiled and clinical experts were asked to identify the degree to which they agreed or disagreed with the information. Those measures agreed on by 70% of respondents were included in this summary. Clinicians had to have cared for at least 30 patients receiving sunitinib. Twelve German clinical experts provided analysis.

Databases searched were PubMed, Embase, Current Contents, and recommendations of oncology societies.

Key topics were sunitinib and tyrosine kinase inhibitor therapy management recommendations.

Arterial Hypertension:

• Mandatory blood pressure monitoring is recommended as often as daily. No clear recommendations exist for monitoring or optimal treatment with antihypertensives. The exact mechanism of effect is unclear, and hypertension may resolve during regular two-week pauses in treatment and reappear with continuation of therapy.
• Agreement was reached on routine exercise, weight control, a sodium-restricted diet, and decreased alcohol consumption.

Fatigue:

• Maintain normal social and physical activity.
• Balance work and sleep schedules.
• Get moderate exercise.
• Measure body weight routinely.
• Use distraction (e.g., reading).
• Offer medical treatment for secondary causes such as hypothyroidism, depression, anemia, or pain.
• Consider reduction of sunitinib in cases with reduced quality of life.

Mucositis/Oral Disorders:

• Avoid irritating food or drinks, such as spicy, acidic, very hot or cold, and dry or hard foods.
• Use lip protection.
• Oral hygiene is important.
• Use of dexpanthenol lozenges and ointment is appropriate for mucosal protection.  
• Oral symptoms should be treated with topical anesthetics, steroids, or anti-infectives.
• In case of pronounced symptoms, consider interruptions of sunitinib.

Diarrhea:

• Advise patients to split food and drinks into small amounts.
• Avoid spicy or fried food and large amounts of fruits and vegetables.
• Maintain sufficient fluid intake.
• Avoid use of laxatives.
• In cases of severe diarrhea, provide IV fluid and electrolytes.  
• Early treatment with agents such as loperamide is advised.
• Interruption or dose reduction of sunitinib was considered appropriate for grade 3 or 4 diarrhea only.

Nausea and Vomiting:

• Eat a bland diet with small servings.
• Use antiemetic drugs such as dopamine agonists and proton-pump inhibitors.
• Sunitinib dosage may be reduced 12.5 mg in cases of grade 3 or 4 symptoms, or if symptom interventions are not successful.

Skin Reactions

Hand-Foot Syndrome:

• Protect the hands and feet from heat and hot water.
• Use cold packs for pain relief.
• Apply moisturizers daily.
• Use systemic anti-inflammatory medication in some cases.
• Use topical antifungals for localized superinfection.
• Use oral ibuprofen or paracetamol for pain control.
• For grade 2 symptoms, consider break-in sunitinib.
• For grade 3 symptoms, interrupt treatment temporarily and use lower doses after symptoms have resolved to lower than grade 1.

Erythema, Dry Skin, and Dermatitis:

• Prevent sun exposure and use ultraviolet (UV) protective lotions with 15 to 30 sun protective factor (SPF).
• Avoid irritating care products.
• Use fatty creams or ointments after showering daily.
• Limit sunitinib dose alterations as much as possible. Only 66% agreement was reached that a treatment break should be considered with grade 2 to 4 skin toxicity.

• Experts were from a single setting, and one author was employed by Pfizer.
• Recommendations were based on the opinion of a few experts, who had limited patient experience with sunitinib. The association with varied levels of evidence to support these recommendations is not evident.
• Advice for patients and physicians was built mainly from the opinions of experts, rather than supporting data from controlled trials.

A significant need exists for more scientific evidence on the prevention and management of side effects caused by these agents for cancer treatment.

To evaluate the effectiveness of a single dose of fosaprepitant in combination with dexamethasone and 5-HT₃ for chemotherapy-induced nausea and vomiting (CINV)

• Patients who were to receive cisplatin were randomly assigned to the experimental group or the control group. The experimental group received a single, 150-mg dose of IV fosaprepitant administered with a 5-HT₃ receptor antagonist and a corticosteroid prior to cisplatin-based chemotherapy. The control group received matched placebos for the experimental regimen and the currently recommended three-day oral regimen of aprepitant for five days after treatment.
• Ondansetron and dexamethasone were administered at current dosing recommendations.
• Patients kept diaries of episodes of vomiting, daily nausea assessment, and use of rescue mediation.
• Adverse effects were assessed at each clinic visit.

• The study consisted of 2,322 participants.
• The median age was 56 years in the experimental group and 57 years old in the control group.
• The study group was 36.7% female and 63.3% male.
• The most frequent diagnosis was lung cancer. Other cancers were GI, reproductive or genitourinary, renal and urinary tract, and breast cancer.
• The study group was 56% white and 29% Asian.
• All patients were scheduled to receive their first course of cisplatin ≥ 70 mg/m².

The study was conducted at multiple outpatient settings in 27 different countries.

All patients were in active treatment.

The study was a double-blind, randomized-controlled, parallel group.

The following measurement tools were used.

• Visual analogue scale (VAS) 100 mm for assessment of nausea
• Daily diary to record vomiting or retching episodes
• Use of rescue therapy (Common Terminology for Adverse Events [CTAE v3.0])

• No significant differences were found between groups for the primary endpoint of no vomiting or retching episodes with no use of rescue medication or episodes during the delayed phase.
• No significant differences were found between groups for the proportion of subjects who reported no significant nausea (defined as < 25 on the VAS).
• Overall, in both groups, slightly more than 74% reported no episodes of vomiting or use of rescue therapy in the delayed phase for nausea.
• Overall, the adverse events seen with the fosaprepitant regimen was similar to that seen with the three-day aprepitant regimen.

• The fosaprepitant regimen as used was as effective for the prevention of acute and delayed nausea associated with cisplatin-based chemotherapy as the currently recommended oral aprepitant regimen.
• A single dose of 150 mg of fosaprepitant was sufficient to suppress delayed CINV for 2–5 days after therapy.

• Findings demonstrated that a single, IV-dose regimen with this agent is an effective alternative to oral neurokinin 1 (NK1) receptor antagonists used as currently recommended for prevention of delayed onset CINV.
• Nurses should be aware of potential infusion-site reactions.
• About one-fourth of patients were refractory to this regimen, indicating the continued need to explore individualized alternatives for maximum symptom control.
• The most effective timing of these treatments for prevention of delayed onset CINV is not yet fully clear.