To evaluate the effectiveness of guideline-consistent versus guideline-inconsistent chemotherapy-induced nausea and vomiting (CINV) prophylaxis on the incidence of CINV in chemotherapy-naïve patients receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC) for the first cycle of treatment

Patients who received HEC or MEC were followed for one chemotherapy cycle. Data were collected from electronic health records for 120 hours postchemotherapy and on days 5–8 during routine follow-up visits.

• N = 1,295
• MEAN AGE = 59.3 years
• MALES: 30%, FEMALES: 70%
• KEY DISEASE CHARACTERISTICS: Breast, lung, lymphoma
• OTHER KEY SAMPLE CHARACTERISTICS: Southeast United States, normal to obese weight, chemotherapy-naïve patients; one-third received HEC, two-thirds received MEC.

SITE: Multi-site  

SETTING TYPE: Outpatient  

LOCATION: Southeast United States

PHASE OF CARE: Active antitumor treatment

APPLICATIONS: Elder care, palliative care

Prospective observational study

• Patient demographics
• Baseline clinical characteristics
• Multinational Association of Supportive Care in Cancer Antemesis Tool (MAT)

The guideline-consistent (GC) group experienced fewer symptoms of CINV than the guideline-inconsistent (GI) group. Significant differences between the GC group and the GI group were found for no CINV (p < 0.001), no emesis (p = 0.027), and no clinically significant nausea (p = 0.001). Of the patients who received HEC, those in the GC group experienced no CINV (p = 0.024) and no clinically significant nausea (p = 0.033). Of the patients who received MEC, those in the GC group experienced significantly less emesis than those in the GI group (p = 0.02).

Adherence to the National Comprehensive Cancer Network (NCCN) guidelines was associated with a reduction of CINV over five days after cycle 1 of chemotherapy. Adherence to NCCN guidelines was low for patients receiving HEC because of omission of corticosteroids in the delayed phase. Adherence in MEC was higher, but would have increased to 98% if a NK₁ receptor antagonist had been prescribed.

• Risk of bias (no blinding)
• Risk of bias (no random assignment)

This is one among other recent studies that have validated the use of guidelines. Patients who received prophylactic treatment per the guidelines had less CINV than patients who did not receive treatment per the guidelines, showing the need to educate oncology nurses on the value of guidelines and the need to collaborate with other healthcare providers. This study did not address low emetogenic potential regimens. This article also showed the helpfulness of extracting data from electronic health records to measure outcomes.

3 ml of iseganan (9 mg) oral solution (n = 251) or placebo, administered as oral rinse six times daily; instructed to rinse mouth with water before each dose, swish study drug to coat all surfaces, gargle and retain for 2 mins, and swallow. (Expectorate if unable to swallow.)

Started study day 1 – within 1 day of chemo or TBI  for a minimum of 10 days, adm for 21 days unless neutrophil recovery with absence of OM.

Follow-up assessment 14 days after adm of study drug disc.
 

The study was comprised of 502 patients, with 251 blinded in each arm. The median age was 48/46.

> 7 yrs and scheduled to receive cytotoxic regimen associated with a >50% incidence of NCI CTC grade > 2 mucositis.
Randomized (stratified by study center and by stomatotoxic trt) strategy 1–non-ablative chemo, 2–ablative cytotoxic therapy followed by auto-SCT, or 3–ablative cytotoxic therapy followed by allogeneic bone marrow or peripheral blood SCT.
 

28 centers in the United States

Nov 2001 – June 2002

Multi site N = 502 large RCT

NCI CTC stomatitis grades, incidence of UOM in eight sites and opioid analgesic use.
Mouth pain and difficulty swallowing was assessed by use of questionnaires.
 

43% trt and 37% placebo patients did not have peak stomatitis, grade = 2, p = 0.182.

No significant difference in severity, incidence, peak mouth pain, peak difficulty swallowing, amountt of opiate, or adverse event type or incidence.
 

Iseganan–did not positively affect the severity of stomatitis or the rate of ulcerative oral mucositis.

H R. Redman and H Fuchs employed by IntraBiotics – probable supporter of study, as articulated in Trotti study.

Findings add to conflicting results in literature regarding efficacy impact of local antimicrobial trt as strategy to reduce severity of stomatitis or UOM.

To evaluate the effects of an organizational intervention to reduce pleural catheter infections

Medical records of patients receiving indwelling pleural catheters (IPC) for malignant effusions were reviewed to describe the overall findings and practices from 2009 to 2014. The protocol was then updated to include changes so that all placements occurred within a single location, all patients received perioperative antibiotics within 60 minutes prior to IPC insertion, and full body sterile draping was conducted. A review of all cases was done after six months of follow-up.

• N = 225   
• MEAN AGE = 63 years
• AGE RANGE = 22–93 years
• MALES: 41.5%, FEMALES: 58.5%
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: Of the patients, 88% had IPC insertion because of malignancy. Lung and breast cancer were most prevalent.

• SITE: Single site   
• SETTING TYPE: Multiple settings    
• LOCATION: Johns Hopkins Medical Institution

• PHASE OF CARE: Late effects and survivorship

• Cohort comparison

• IPC infection defined as either cellulitis and/or tunnel infection
• Pleural space infection defined by draining of pus from the pleural space or a positive culture of pleural fluid with associated clinical symptoms

Overall, the IPC infection rate was 8.2% prior to the intervention and decreased to 2.2% after the intervention (p = 0.049).

The quality improvement interventions implemented were associated with a significant reduction in overall IPC infection rates.

• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement validity/reliability questionable
• Reliance on medical records data

This study showed that a quality improvement intervention involving a review of practices and related outcomes and an implementation of protocol changes aimed at reducing IPC infection rates was successful because of the overall reduction of infection rates. Principles related to surgical site infection and catheter infection prevention were incorporated into the organizational protocol changes that were made.

Intervention treatments were individualized based on patient scores on specific questionnaires that measured the six modules (perpetuating factors) of postcancer fatigue. These included:

1. Insufficient coping with the experience of cancer
2. Fear of disease recurrence
3. Dysfunctional cognitions concerning fatigue
4. Dysregulation of sleep
5. Dysregulation of activity
6. Low social support and negative social interactions.

If a patient had a score on a questionnaire that indicated problems in a specific module, the accessory module became part of the treatment. Therapy only varied in the number of modules, but within each module, the therapy was standardized. The intervention was delivered by three therapists with previous experience with patients with chronic fatigue. Therapy sessions ranged between five and 26 sessions (mean = 12.5 sessions [standard deviation = 4.7 sessions]), with a duration of one hour during a six-month period. Cognitive and behavioral techniques used in therapy addressed the six modules of postcancer fatigue. Patient outcomes were assessed at baseline and six months after enrollment.

• In total, 98 patients with cancer were included.
• The ratio of males:females was almost equal.
• There were multiple diagnoses, the most common being breast cancer (about 30% in both groups).
• Patients in the waiting list condition underwent chemotherapy more often and had less psychological distress compared with patients in the intervention group.
• Participants were excluded if they were receiving current psychological/psychiatric treatment, were younger than 18 years, or were older than 65 years.

• Outpatient clinics of medical oncology, urology, surgery, orthopedic, hematology, and gynecology 
• The rationale for the intervention was based on the model of precipitating and perpetuating factors.

Patients were undergoing the active treatment phase of care.

The study was a randomized, controlled trial with a

1. Cognitive-behavioral therapy (CBT) intervention (n = 50)
2. Waiting list condition (patients were told that they could start the intervention after the second assessment) (n = 48).

Checklist Individual Strength (CIS)

Patients in the CBT intervention group experienced a statistically significant decline in fatigue severity (difference, 13.3; 95% confidence interval [CI] [8.6, 18.1]), as well as functional impairment (difference, 21.6; 95% CI [12.7, 30.4]) compared with patients in the waiting list condition (p < 0.001). The proportion of patients with significant improvements in fatigue severity and functional impairment was significantly higher than the intervention condition compared with the waiting list condition, indicating clinical significance (p < 0.001).

• The study was limited to patients younger than 65 years; however, 50% of cancer is diagnosed after this age.
• Controlled follow-up was not possible because patients in the waiting list group were offered CBT after the six-month assessment.
• There was no attention placebo control goup; therefore, the possibility cannot be ruled out that attention played a role in the improvements observed in the intervention group.

To systematically review current evidence for prevention and treatment of gastrointestinal (GI) mucositis in adults and children receiving cancer treatment and to update relevant Multinational Association of Supportive Care in Cancer (MASCC) guidelines

This was an evidence-based guideline developed based on a systematic review of the literature with rating of levels of evidence and identification of study flaws.

Database searched was MEDLINE.

Search keywords were numerous and included all known possible interventions tested.

Inclusion and exclusion criteria were not stated in this article but provided elsewhere in the journal.

• Patients were undergoing the active treatment phase of care.
• The study has clinical applicability for pediatrics.

A total of 1,336 papers were initially retrieved; of these, 146 were reviewed for development of the guidelines.

• Probiotics with Lactobacillus spp. may be beneficial for prevention of chemotherapy- and radiotherapy-induced diarrhea in patients with pelvic malignancies. Two studies with positive results were cited.
• Amifostine may reduce esophagitis because of concomitant radiation and chemotherapy. It is not recommended in other situations because of conflicting evidence.
• Mesalazine, 5-aminosalicylic acid (5-ASA), and olsalazine are not recommended because they have been associated with increased diarrhea compared to placebo.
• Sucralfate is not recommended for diarrhea prevention because it is associated with increased GI side effects, including rectal bleeding.
• Oral sulfasalazine given at 500 mg twice daily is recommended to reduce incidence and severity of radiation-induced enteropathy.
• No guideline was provided for glutamine, but three new studies were sited that showed promising results.
• If loperamide has not resulted in diarrhea control with standard or high-dose chemotherapy in HCTY patients, 100 mcg or greater of subcutaneous octreotide twice daily is recommended.

This review had a limited search strategy, as only one database was searched. In addition, most of the suggestions and recommendations provided were based on low-level evidence by the rating system used.

These guidelines provide some suggestions for management of oral mucositis and diarrhea in patients with cancer. They also provide information regarding evidence for mucositis in the entire GI tract.

To demonstrate the benefits and tolerance of a multicomponent herbal oral agent for mucositis in patients with head and neck cancer receiving radiation or combination therapy

Orasol plus solution (a mixture of lapacho, hyaluronic acid, green tea, calendula, erisiom, propolis, marigold, plantain, and mauve) was administered to patients from the first day of radiotherapy until the end of therapy. It was given at a dose of 10 ml three times daily. The authors indicated that it can be swallowed, but did not state how patients were instructed to use it.

• N = 40
• AGE = 70% were older than 60 years
• MALES: 68%, FEMALES: 32%
• KEY DISEASE CHARACTERISTICS: Patients had head and neck cancer. The primary site of cancer was the oral cavity in 30% of patients and the hypopharynx in 30%. In addition, 72.5% were getting radiation only, and the rest were getting radiation and chemotherapy
• OTHER KEY SAMPLE CHARACTERISTICS: Thirty-five percent were current smokers.

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

• PHASE OF CARE: Active antitumor treatment

• Phase II prospective trial

• Common Terminology Criteria for Adverse Effects (CTCAE) version 4

Of the patients, 47.5% developed grade 1, 27.5% developed grade 2, and 10% developed grade 3 mucositis. Median Gy doses to the oral mucosa were lowest in those with grade 1 mucositis. Six patients did not develop mucositis. None of these patients was receiving radiation and chemotherapy. The prevalence of grade 2 or greater mucositis was higher among smokers (p < 0.02). One patient developed itching and one developed glossitis. Twenty-five percent needed an increase in dosage or additional analgesic therapy.

The herbal nutritional supplement tested here may have some benefit for the prevention of severe mucositis in patients with head and neck cancer during therapy. Additional research is needed to establish any benefit.

• Small sample (< 100)
• Baseline sample/group differences of import
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• No information is given regarding patient adherence to use. The sample was too small for subgroup analysis for those getting combination chemoradiation therapy.

Very few interventions have been shown to be effective for the prevention and treatment of oral mucositis in patients receiving cancer treatment. The substance tested here appeared safe, and findings suggest that it may be beneficial; however, numerous study design limitations exist. Further research with this agent is needed to determine efficacy.

To compare the efficacy and safety of ondansetron, granisetron, and palonosetron used with equal dosage of dexamethasone with moderately emetogenic chemotherapy (MEC) to highly emetogenic chemotherapy (HEC)

• Patients were assigned randomly to receive either 8 mg ondansetron on days 1 and 2, 3 mg granisetron on days 1 and 2, or 0.75 mg palonosetron on day 1, 30 minutes prior to chemotherapy.
• All patients received 16 mg of IV dexamethasone on day 1, and 4 mg on days 2 and 3.
• Patients were followed for 5 days for efficacy and 8 days for safety evaluation.

• The study consisted of 1,213 participants.
• The ondansetron arm had 616 participants, the granisetron arm had 440 participants, and the palonosetron arm had 157 participants. 
• Median age was 64 years old.
• More than half of the group was female (54.2%).
• Diagnoses were not reported. 
• More than three-fourths of the group (76%) had received prior chemotherapy.
• Patients receiving HEC regiments, chiefly involving use of cisplatin, represented 40% of the sample. The rest of the sample were receiving MEC regimens, including lower-dose cyclophosphamide and doxorubicin.

The study was conducted in a single outpatient setting at Bankura Smmilani Medical College and Hospital in India.

All patients were in active treatment.

This was a double-blind, randomized controlled trial.

• Complete response (CR) was defined as no emetic episodes, no rescue medication use, and no more than mild nausea.
• Partial response (PR) was defined as less than one vomiting episode or moderate nausea for a maximum of four hours.
• Treatment failure was defined as two or more vomiting episodes, severe nausea, or nausea lasting more than hours.
• The method of rating nausea severity was not described.
• The method for data capture was not described.

• No significant differences were found between groups in antiemetic side effects.
• Overall, across both HEC and MEC groups, palonosetron was found to be the best acting drug (87.8% CR), following by ondansetron (77.2% CR) and granisetron (76.6% CR) (p = 0.021).
• In the HEC group, no differences were found in antiemetic response across the treatment groups.
• Within the first 24 hours, in the MEC group, among those receiving palonosetron, 92.5% had CR, compared to 83.6% of those receiving granisetron and 76.8% receiving ondansetron (p = 0.01).
• Palonosetron also was slightly more effective in the delayed phase of nausea and vomiting (p = 0.02).
• Headache and constipation were the most common side effects.

• For patients receiving MEC, palonosetron was more effective than granisetron and ondansetron for the prevention and control of chemotherapy-induced nausea and vomiting (CINV) in the acute phase.
• No significant differences were found in efficacy for patients receiving HEC.

• Limited information about diagnostic information was provided, and no subgroup analysis was conducted for those who were chemotherapy naïve versus those who had received prior emetogenic therapy.
• No description was provided of the actual methods for data collection used, and no description was provided regarding how nausea severity was measured.

Study findings suggest that palonosetron may be more effective for CINV prevention and control with MEC. Palonosetron, as pointed out in this article, is much more expensive than the other medications used, so considering its use in the type of chemotherapy treatment where it appears to be more effective makes sense. Differences in efficacy seen over time suggest that the same drug may have the same efficacy in a patient over the course of therapy. Consideration might be given to studying this issue and the potential of switching drugs at various points.

Investigate omega 3 fatty acids in reducing the incidence and severity of paclitaxel-induced peripheral neuropathy

Patients were randomly assigned to receive omega 3 fatty acid supplements at a dose of 640 mg three times daily, or an identical gelatin placebo capsule. All patients received the intervention throughout treatment and for one month after chemotherapy treatment. Patients were evaluated prior to chemotherapy and one month after completion of chemotherapy. Evaluations were done by a single neurologist.

• N = 57           
• MEAN AGE = 45.9
• FEMALES = 100%
• KEY DISEASE CHARACTERISTICS: All had breast cancer and were receiving four courses of 175 mg/m² paclitaxel for positive node disease.

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

PHASE OF CARE: Active antitumor treatment

Double-blind, placebo-controlled, randomized trial

• Total peripheral neuropathy score including sensory symptoms, pin sensibility, tendon reflexes, and nerve conduction studies of sural and peroneal nerves from scores for individual items of 0-4
• Unilateral nerve conduction studies
• Serum concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)

70% of patients receiving omega 3 fatty acid supplements did not develop peripheral neuropathy, compared to 40% in the placebo group (odds ratio = 0.3, .95% CI = 0.10–0.88, p = .029). There was a non-significant trend toward lower severity of symptoms in those receiving omega 3 fatty acids. No significant differences existed between groups in individual nerve conduction study results. Significant differences did exist between groups in serum EPA and DHA concentrations (p < .005) with higher levels in the experimental group. No relationship existed between serum concentrations and peripheral neuropathy scores.

Findings suggest that oral supplementation with omega 3 fatty acids may have a protective effect for development of peripheral neuropathy in patients receiving paclitaxel.

• Small sample < 100
• Measurement/methods were not well described.
• Measurement validity/reliability was questionable.
• Findings were not generalizable.
• Study was underpowered by the authors’ report and calculations.
• The specific grading of findings to calculate the peripheral neuropathy score is not well defined and is not a commonly used and validated scoring approach.
• There was a limited timeframe of follow-up. 
• Findings may not be applicable in patients receiving different neurotoxic drugs.

Findings suggest a neuroprotective effect of omega 3 fatty acid supplementation. These are promising results, which warrant further research in well-powered studies and in the context of other types of neurotoxic chemotherapeutic agents.

To assess the effectiveness of palifermin in preventing mucositis in children with acute lymphocytic leukemia (ALL) undergoing chemotherapy

A clinical trial of 90 children with ALL who were randomized to receive chlorhexidine or palifermin. One group received 60 mcg/kg palifermin as an IV bolus once daily three days before and three days after chemotherapy. The other group received chlorhexidine mouthwash administered once daily three days before and three days after chemotherapy.

• N = 90   
• AGE = 5–18 years
• MALES: 44, FEMALES: 46
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: ALL 
• OTHER KEY SAMPLE CHARACTERISTICS: Induction chemotherapy protocol consisted of standard risk B-precursor ALL (COG)/dexamethasone, vincristine, L-asparaginase, intrathecal (MTN + Ara C + hydrocortisone). The intensification protocol was dexamethasone, vincristine, L-asparaginase/dexamethasone, cyclophosphamide/6-thioguanine + cytarabine + intrathecal MTX.

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: Tehran, Iran

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

Randomized, controlled trial

The World Health Organization (WHO) Oral Toxicity Scale was used for grading mucositis. The data were analyzed with two-way ANOVA.

The group that used the palifermin had a decreased incidence and severity of chemotherapy-induced mucositis.

Palifermin reduced oral mucositis in children with ALL.

• Small sample (< 100)
• Risk of bias (no blinding)

In this study, palifermin has reduced the severity of mucositis in children with ALL who received induction and intensification chemotherapy.

To determine whether improved pain control and/or ulcer management of oral mucositis in patients with head and neck cancer receiving postoperative radiation therapy can be achieved with licorice mucoadhesive film or triamcinolone acetonide mucoadhesive film

When patients reached a World Health Organization (WHO) grade 2 or 3 mucositis rating, they were randomized according to a balanced block randomization to receive either triamcinolone (T) (.5 mg triamcinolone acetonide in film) or licorice (L) (.18 mg polyphenols as pyrogallol extracted from licorice root) in addition to the standard of care. The standard of care included frequent mouth rinses using boiled water, regular brushing and flossing, scaling, and the removal of plaque and tartar during radiation therapy. The films were applied to the upper lip four times per day. The intervention continued for four weeks or until the cessation of mucositis. The use of analgesics was not permitted before or during the study. Two investigators rated the severity of the mucositis, and data were collected on a weekly basis. Compliance was measured by counting unused films.

• N = 60  
• AVERAGE AGE = 57.93 years
• MALES: 60% (T group); 63.3% (L group), FEMALES: 40% (T group); 36.7% (L group)
• KEY DISEASE CHARACTERISTICS: This study included patients with head and neck cancer (documented histologically) undergoing radiation therapy with grades 2 and 3 oral mucositis as determined by the WHO scale.
• OTHER KEY SAMPLE CHARACTERISTICS: Patients were older than 18 years. The ability to continue throughout the entire study was required. The study included men and nonpregnant women. The study excluded patients undergoing chemotherapy and immunotherapy or taking investigational drugs. The study excluded patients with a significant history of drug or alcohol abuse and pregnant women.

• SITE: Single-site    
• SETTING TYPE: Inpatient    
• LOCATION: Isfahan, Iran

• PHASE OF CARE: Active antitumor treatment

Double-blinded, prospective, randomized, controlled trial

• World Health Organization (WHO) mucositis scale
• Data forms
• Visual Analog Scale (VAS)

There was a significant difference in the mean value of the mucositis scores for the T and L interventions when compared to the control group (p < .05) although there was no difference between the two intervention groups. No statistically significant difference was achieved (p > .05) between interventions in reducing pain during radiation therapy. However, each was statistically significant (p < .05) in reducing pain during radiation therapy when compared to the standard of care alone. A slight additional reduction in pain was noted in the L group, but it was not significant.

Both triamcinolone acetonide mucoadhesive film and licorice mucoadhesive film reduced the mean mucositis score and the pain associated with mucositis during radiation therapy when compared to the group that only received standard of care. However, there was no significant difference between the two interventions for mucositis scores or pain scores when compared to each other.

• Small sample (< 100)
• Findings not generalizable
• Other limitations/explanation: State-run cancer center; convenience sampling; pre-existing oral complications

Although there is not enough evidence to recommended the use of this intervention, this study is a good starting point for nurse research to continue working toward finding additional, better ways to treat and prevent oral mucositis and its complications in patients undergoing cancer treatment.