RESOURCE TYPE: Evidence-based guideline

PHASE OF CARE: Active antitumor treatment

An initial search resulted in 1,162 citations, which were delimited to 277 references that contributed to these guidelines. High-level evidence findings were included as well as a review of lower-level evidence by panel members in areas where high-level evidence was lacking.

Algorithms were established for the use of antifungal and antiviral therapies and the use of vaccinations, specifically therapeutic drug monitoring of azoles; enhanced recommendations for HBV, HCV, and HIV; and vaccination utilization (outlined by disease/therapies and level of risk, p. 884–890). Overall, infection control should include prophylactic anti-infective therapies, per protocol per case, as well as ensure standards of care (e.g., hand hygiene). Considerations for susceptibility and resistance are paramount.

• No major limitations were noted. These werecomprehensive guidelines from a national work group.

Assessment of patient diagnosis, treatment, and preexisting comorbidities (e.g., HSV, HIV, CMV) can guide proper prophylactic anti-infective agents and vaccines. Together with following standards of practice (e.g., hand hygiene), nurses can optimize infection control.

To compare the effectiveness of antiemetic regimens including ondansetron with and without aprepitant to prevent chemotherpy-induced nausea and vomiting (CINV)

Patients were randomized to receive (a) an antiemetic regimen consisting of ondansetron 8 mg IV 30 minutes before chemotherapy followed by 24 mg IV in a continuous infusion daily till 6–12 hours after the last dose of chemotherapy or (b) the same ondansetron regimen with the addition of oral aprepitant 125 mg 6–12 hours before chemotherapy and 80 mg daily till one day after the last dose of chemotherapy. Data were collected for six days following chemotherapy administration.

• N = 83
• AVERAGE AGE = 51 years
• MALES: 56%, FEMALES: 44%
• KEY DISEASE CHARACTERISTICS: Acute myeloid leukemia, high-risk myelodysplastic syndrome, or chronic myeloid leukemia in blast phase
• OTHER KEY SAMPLE CHARACTERISTICS: Receiving cytarabine-based chemotherapy at a dose ≥ 1 g/m² per day for at least three days

• SITE: Not stated  
• SETTING TYPE: Not specified    
• LOCATION: Not described

• PHASE OF CARE: Active antitumor treatment

Randomized, controlled trial

• Not well described
• Daily diary to record episodes of nausea or vomiting and any rescue medications needed

There were no statistically significant differences in the prevention of CINV or use of rescue medications between the two arms.

There was no difference in CINV prevention between antiemetic regimens of ondansetron with or without aprepitant.

• Small sample (< 100)
• Risk of bias (no blinding)
• Measurement/methods not well described
• Measurement validity/reliability questionable

There was no significant difference between antiemetic regimens of ondansetron with or without aprepitant in the prevention of CINV. There may not be a benefit to adding aprepitant to standard antiemetic therapy in this population of patients.

The purpose of the study was to evaluate incidence of febrile neutropenia and grade 4 neutropenia after receiving lenograstim prophylaxis.

All patients received G-CSF prophylaxis with 263 mcg from days 5–9 in patients receiving three cycles of epirubicin and ifosamide for soft tissue sarcoma. Patients were observed for three cycles. Blood counts were done on days 8,15, and 22.

• 36 total participants
• Median age was 53, range was 19–72
• 48% were male, 52% were female
• All had soft tissue sarcoma and were receiving chemotherapy regimens associated with a 50% risk of febrile neutropenia 
• All patients were chemotherapy naive.

• Single site
• Outpatient
• Italy

Active antitumor treatment

Observational

• CTCEA [v.4.03]
• Febrile neutropenia was defined as an absolute neutrophil count of less than 1,000/mm³ and single temperature greater than 38.3ºC.

There were no episodes of febrile neutropenia. Grade 4 neutropenia was seen in 17% of patients—58% on day 8, 29% on day 15, and 13% on day 22.  No treatment delays or dose reductions were required.

G-CSF as given here was effective in preventing the risk of febrile neutropenia and grade 4 neutropenia in patients receiving chemotherapy associated with high risk for these adverse events.

• Small sample (less than100)
• Risk of bias (no control group) 
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Risk of bias(sample characteristics)
• Findings not generalizable
• Homogenous group of patients receiving the same chemotherapy regimen
• Findings may not be generalizable to other groups

Prophylactic G-CSF reduced risk of febrile neutropenia and grade 4 neutropenia in patients at risk for these problems during chemotherapy for soft tissue sarcoma. The most appropriate timing of prophylactic colony-stimulating factor is not clear. The timing studied here appeared to be effective.

STUDY PURPOSE: To investigate the effectiveness of ginseng supplements for reduction of fatigue and enhancement of physical performance

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 12, 4 on fatigue reduction and 8 for physical performance 
• TOTAL PATIENTS INCLUDED IN REVIEW = 458 for fatigue, 212 for performance
• SAMPLE RANGE ACROSS STUDIES: 19–271
• KEY SAMPLE CHARACTERISTICS: Most studies were of healthy adults. One study on cancer, one on multiple sclerosis, and one on chronic idiopathic fatigue

PHASE OF CARE: Not specified or not applicable

Ginseng supplements were associated with an overall standard mean difference of 0.34  (95% confidence interval [0.16, 0.52]) for fatigue reduction; however, duration of use was only six weeks or less, and doses of less than 1000 mg/day showed no effect. No effect was seen for physical performance.

Ginseng may be helpful for fatigue reduction; however, this analysis included few studies and only one study on individuals with cancer. This analysis provides insufficient evidence to draw firm conclusions.

• Limited number of studies included
• Low sample sizes
• Authors stated that numerous randomized, controlled trials were excluded because of insufficient data.

Limited evidence exists to show the efficacy of ginseng supplements overall for fatigue reduction, and evidence here does not show any improvement in physical performance with ginseng.

To evaluate the effects of listening to music and poetry on pain, depression, and hope

Patients were randomly selected for inclusion and then randomly assigned to listen to instrumental music or poetry readings on a MP3 players or to a control group. Therapies were offered for three days and for 30 minutes at a time. Study measurements were obtained before and after the intervention on day 1 and again on the last day. Listening was monitored. The daily variations in pain of the music and poetry group were compared to those of the control group.

• N = 65   
• AGE RANGE = 18 years to older than 60 years
• MALES: 28%, FEMALES: 72%
• KEY DISEASE CHARACTERISTICS: Various tumor types
• OTHER KEY SAMPLE CHARACTERISTICS: Of the participants, 38% were receiving NSAIDs and weak opioids, and 43% were receiving NSAIDs and strong opioids.

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: Brazil

Randomized, parallel-group, prospective trial

• Visual analog scale (VAS) for pain
• Beck Depression Inventory (BDI)
• Herth Hope Scale

Listening to music was associated with improvement in pain (p < 0.001) and depression (p = 0.004). Listening to poetry was associated with improvement in pain (p < 0.001), depression (p = 0.001), and hope (p = 0.009). Individuals with either intervention had improvement in pain compared to the controls (p < 0.001), but no difference was observed in other outcomes.

Listening to music or poetry reading may help in the management of pain and depressive symptoms.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Unintended interventions or applicable interventions not described that would influence results
• Measurement/methods not well described
• Although measurements were conducted at several time points during the study, the actual measurement used for reporting was not specified.
• No information was provided on the reason for patient hospitalization. 
• No information was provided regarding analgesic dosages or changes during the study period.

Listening to music or poetry may be beneficial to patients in the management of pain and dealing with depressive symptoms. Flaws in this study limit the strength of these findings; however, these are low-risk and low-cost interventions that might be beneficial. The type of music and poetry would likely affect the results for various patients.

To compare the efficacy, safety, and cost of olanzapine-based triplet antiemetics compared to the use of aprepitant as part of antiemetics in chemotherapy-naïve patients receiving highly emetogenic chemotherapy

The olanzapine group received 10 mg olanzapine orally (PO), 0.25 mg palonosetron intravenously (IV), and 20 mg dexamethasone IV on day 1; and then 5 mg olanzapine PO and 4 mg dexamethasone PO on days 2–4. The aprepitant group was given 125 mg aprepitant PO, 0.25 mg palonosetron IV, and 12 mg dexamethasone IV on day 1; 80 mg aprepitant PO on days 2 and 3; and 4 mg dexamethasone PO on days 2–4. Patients were asked to record the intensity of nausea, the use of rescue medication, and vomiting daily in a diary. Patients were contacted daily for reminders to record symptoms.

• N = 100   
• MEAN AGE = 43.6 years
• MALES: 30%, FEMALES: 70%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Patients had various tumor types, and the majority were breast cancer.
• OTHER KEY SAMPLE CHARACTERISTICS: The study included patients receiving various types of highly emetogenic chemotherapy, and all received six cycles.

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: India

PHASE OF CARE: Active antitumor treatment

• Prospective, two-group, non-randomized trial

• Visual analog scale (VAS) for nausea intensity 
• CTC
• Complete response defined as no emesis and no rescue medication
• Complete response recorded for acute, delayed, and overall periods

No significant differences existed between groups in complete response rates or nausea severity. No grade 3 or 4 toxicities existed. Adverse events associated with olanzapine were sedation and dizziness in less than 10% of patients.

Olanzapine-based triplet antiemetic therapy was as effective as aprepitant-based triplet antiemetics in this study.

• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• No information provided on timing of measurements analyzed or trends over time
• No information on rescue medications used

Findings suggest that the use of olanzapine in substitution for an NK1 in a triplet antiemetic regimen was effective. The study is limited by its lack of random assignment to study groups, but the groups were well matched on most demographic and other treatment variables. Olanzapine is much less expensive than an NK1 and may be a good alternative for patients who have limited financial resources or insurance coverage for antiemetics.

To determine the effect of Calendula officinalis flowers extract mouthwash as an oral gel on radiation-induced oropharyngeal mucositis (OM) in patients with head and neck cancer and to determine possible mechanism of action; total antioxidant, polyphenol, and flavonoid content; and quercetin concentration of mouthwash

Patients were randomly assigned to either the calendula mouthwash group or a placebo group. Both solutions were in a gel formation. Patients were to use 5 ML solution twice per day (every 12 hours) and hold the solution in the oral cavity for at least one minute.

Assays were done to assess antioxidant activity, phenol content of the mouthwash, and flavonoid content. Two physicians performed mucositis grading and grading of oral ulcers.

• The study reported on 38 patients with an age range of 46–72 years.
• The sample was 50% male and 50% female.
• Patients were diagnosed with head and neck cancer and receiving curative radiotherapy or chemoradiotherapy. Radiotherapy was prescribed at 30–35 sessions for seven weeks with a cumulative dose of 6000–7000 cGy.
• Patients with comorbidities, poor oral hygiene, or receiving concurrent medications were excluded.

The study was conducted at a single outpatient site in Babolsar, Iran.

Patients were undergoing the active antitumor treatment phase of care.

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

The Oral Mucositis Assessment Scale (OMAS) was used.

No patients in the treatment group required medication for OM, and radiation was not stopped for mucositis. Three patients in the treatment group did not develop OM during the whole treatment period. Overall OMAS scores were significantly lower in the treatment group at weeks 2, 3, and 6 of the study (p < 0.001).

Calendula-containing oral mouthwashes may be effective in decreasing OM intensity in this patient population.

The authors make reference to some participants withdrawing, but numbers of participants do not seem to reflect this. The number of patients analyzed and the number of patients reported as leaving the study do not add up correctly. Reasons for study withdrawal are not fully described. Very little data are presented in the article. 

Oral use of a calendula-containing agent might be an effective and simple intervention. The agent was prepared specifically for this study; therefore, availability of the agent is not clear. No conclusions can be drawn from this study alone, but, given the promising results and lack of known effective preventive agents, further research in this area would be helpful.

To evaluate evidence regarding the prevention and management of epidermal growth factor receptor–inhibitor (EGFRI)-related skin toxicities. Secondary objectives were to review current knowledge on (a) the pathophysiology of this type of skin toxicity, (b) prediction of the occurrence of (severe) skin toxicity in individual patients, (c) the need for adequate management of skin toxicities, and (d) the possibility of any interference between management of skin toxicities and the antitumor effect of EGFRIs.

The database searched was MEDLINE.

Search keywords were skin toxicity, rash, acneiform rash, acne, exanthema, cetuximab, panitumumab, erlotinib, gefitinib, lapatinib, monoclonal antibodies, EGFR, antibiotics, antibody dependent cell mediated cytotoxicity, ​and NK cells.

Studies were included in the review if they reported on the testing any type of management (prophylactic as well as reactive) using topical agents, systemic agents, or both.

Exclusion criteria were not specified.

A total of 283 references were retrieved. No quality rating or method of study evaluation was described.

• Eighty final studies were included, with five randomized controlled trials comprising 338 patients.
• The samples across studies ranged from 16 to 110 patients.

Patients were undergoing the active antitumor treatment phase of care.

• Reviews with findings regarding the pathophysiology of skin toxicities, factors that predict skin toxicity, and potential interactions between the management of skin toxicities and antitumor effects of EGFRIs concluded that skin toxicities should be prevented or managed because of their impact on quality of life.
• The studies also provided a review of clinical trials for the prevention and management of skin toxicities. They noted the lack of a strong evidence base, and that tetracycline derivatives have the strongest evidence, despite review findings of conflicting results in this area.

A strong evidence base is lacking for any recommendations on the prevention and management of skin toxicities with EGFRIs.

• How evidence was evaluated or graded is unclear.
• Recommendations were made for tetracyclines, despite the review of evidence showing conflicting results.
• The search was limited, with only one database used.

This review adds to the current observation that a lack of strong evidence exists for any specific set of interventions to prevent or manage skin toxicities in patients receiving EGFRIs. However, the review suggests that the prior belief in letting skin effects go uncontrolled, as they were seen as an indicator of an antitumor treatment effect, is not appropriate.

To evaluate the impact of rehabilitative, medical, and physical therapies or a lack of these interventions on the development of breast cancer-related lymphedema

This was a retrospective study of the medical records and follow-up forms of 5,064 women with breast cancer between 1995 and 2010. Preoperatively, all patients were instructed in risk reduction behaviors (no needles and no blood pressure measurements on the affected side). During the postoperative period, pressure dressings on the axillary fossa and flap region were used during the first five days. Venous cannulation was avoided in the involved arm during the first two postoperative years. Patients attended routine follow-up visits. Patients who received adjuvant radiotherapy also were treated in the axillary area. Cyclophosphamide, adriablastin, 5-fluorouracil, and docetaxel were used for first-line adjuvant chemotherapy. All patients were referred to physiotherapy and the rehabilitation clinic postoperatively. Patients were taught daily self-drainage massage techniques and flexibility and strength exercises. Patients were educated about lymphedema symptoms, skin care, and general protective measures, and they were given written materials.

• N = 5,064
• MEDIAN AGE = 51 years (range = 34–75 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Patients with stages 2 and 3 breast cancer 
• OTHER KEY SAMPLE CHARACTERISTICS: Modified radical mastectomy with levels 1–3 axillary dissection; Stewart transverse incision; Cooper’s ligaments involved; axillary dissection included dissecting under the pectoralis minor muscle; exclusion criteria included limb trauma, vascular disease, thromboembolic events, neoadjuvant chemotherapy or radiotherapy, uncontrolled diabetes, cardiovascular disease, or history of serious infection or surgery on the affected side

• SITE: Single site    
• SETTING TYPE: Not specified    
• LOCATION: Turkey

• PHASE OF CARE: Multiple phases of care

Retrospective, two-group design (physiotherapy group participated in physiotherapy and did exercises regularly, no physiotherapy group did not receive physiotherapy or did not do exercises regularly)

• Difference in circumference measured pre- and postoperatively > 5%

Overall, 19.9% of patients developed lymphedema. It was significantly less common in patients who participated in physiotherapy than in those who did not (p <  0.001), and it was more common in patients with a body mass index (BMI, kg/m²) between 30–34.9 than in those with lower BMIs (p < 0.001).

Educating patients about the risk factors (e.g., weight management) of lymphedema and referring them to postoperative physical therapy and rehabilitation clinics may be an important way to prevent postoperative lymphedema.

• Risk of bias (no random assignment)
• Other limitations/explanation: Retrospective design; single-site study

Educating patients about the risk factors for developing lymphedema pre- and post-treatment is important. All patients who received aggressive surgeries and do not have lymphedema will benefit from referral to a physical therapy program to teach exercises. Nurses can teach risk reduction guidelines.

To empirically explore whether omitting paracetamol was clinically feasible in concurrent strong opioid therapy when treating incurable patients with cancer receiving palliative home care

Researchers assessed the difference in pain control in patients initially on a strong opioid in combination with paracetamol, over a four-day period, versus a strong opioid alone without paracetamol. Patients were asked to estimate their pain intensity at baseline, and then to stop paracetamol. If pain increased, patients were to take an extra dose of the opioid. If this was not effective, the paracetamol was restarted.

• The study reported on a sample of 34 patients.
• Median patient age was 68 years (range = 48–88 years).
• The sample was 53% male and 47% female.
• Prostate, pancreatic, breast, gynecologic, and bladder cancer were the most common patient diagnoses.
• Pain was classified as nociceptive (56%), neuropathic (15%), and mixed (29%).
• Median dose of strong opioids was 90 mg morphine equivalents every 24 hours.

• Multisite
• Home setting
• Three palliative homecare teams in Sweden

The study used a prospective, descriptive, cohort design.

• Numeric rating scale (0–10)
• Interview

Only six patients (18%) wanted to continue with regular paracetamol, while 10 appreciated the opportunity to take paracetamol only as needed. There was no significant difference in average pain intensity with or without paracetamol. On day 4 at follow-up, 26% felt more pain, 6% felt less pain, and 68% reported no difference.

The study supported the hypothesis that a fair number of patients on strong opioids do as well without paracetamol.

• The study had a small sample, with less than 100 participants.
• The study occurred over a short interval of time.

The decision to utilize a combination of a strong opioid and paracetamol/acetaminophen should not necessarily be mandatory. It should be individualized for each patient, as there are patients who achieve pain control on the strong opioid alone, thus alleviating the need for additional medication in combination.