DOI Link: doi: 10.12788/jcso.0245

To compare the effectiveness of an olanzapine-based triple-drug antiemetic regimen with a fosaprepitant-based triple-drug regimen

Patients were randomized to either olanzapine, palonosetron, and dexamethasone (OPD) or fosaprepitant, palonosetron, and dexamethasone (FPD) before the first course of chemotherapy. The OPD regimen was palonosetron 0.25 mg and dexamethasone 20 mg IV prior to chemotherapy and 10 mg PO olanzapine on days 1–4. The FPD regimen was 12 mg dexamethasone, 0.25 mg palonosetron and 150 mg fosaprepitant IV prior to chemotherapy, followed by oral dexamethasone 4 mg twice daily on days 2–3. Patients were allowed to take rescue medication. All patients received a placebo to ensure that the medication provided looked identical to the patient. Daily episodes of vomiting, symptom intensity, and use of rescue therapy were recorded by the patient in a diary for five days.

• N = 101   
• MEDIAN AGE = 62 years
• AGE RANGE = 52–76 years
• MALES: 78.2%, FEMALES: 21.8%
• CURRENT TREATMENT: Combination radiation and chemotherapy
• KEY DISEASE CHARACTERISTICS: Patients with locally advanced head and neck or esophageal cancer receiving HEC and daily radiotherapy

• SITE: Multi-site   
• SETTING TYPE: Outpatient    
• LOCATION: United States

PHASE OF CARE: Active antitumor treatment

• Single-blind, placebo-controlled, randomized trial

• MD Anderson Symptom Inventory (MDASI) mean of daily MDASI scores was used in analysis
• Visual analog scale (VAS) for nausea severity
• Complete response defined as no emesis and no use of rescue medication

No difference existed between groups in complete response for the acute period. For the delayed and overall periods, those on the olanzapine regimen showed a CR rate of 76% compared to 74% in the comparison group. Twelve percent of the OPD group required rescue during the acute phase, and 12% required rescue medication during the delayed period. In the FPD group, 10% required rescue during the delayed phase, and 26% required rescue medication in the acute period. The percentage of patients with no nausea was higher in the OPD group in all phases (p < 0.01). Patients on olanzapine had more drowsiness that was resolved by day 3–4.

Findings suggest that both the standard triple-drug antiemetic regimen and the olanzapine-based regimen were effective in controlling vomiting. As a greater proportion of those receiving olanzapine had no nausea, the olanzapine regimen may provide greater nausea control.

This study showed that both antiemetic regimens were similar in terms of control of emesis and need for rescue medications, and that nausea was better controlled with olanzapine. Nausea has been more difficult to control with currently used antiemetic regimens. These results suggest that olanzapine-based regimens may provide better nausea control. Olanzapine is also generally much less expensive than NK1s, providing a good treatment alternative at a lower cost.

DOI Link: doi: 10.1016/S1470-2045(13)70009-3

To determine the acceptability of solely using palliative noninvasive ventilation (NIV) versus oxygen therapy to manage breathlessness in patients with end-stage cancer and its effects in reducing dyspnea and opioid requirement

• All patients received a 5–10 minute demonstration on NIV prior to randomization.
• Patients were randomly assigned to either NIV (pressure-support mode and initiation based on patients’ request and mask comfort) or oxygen (Venturi or reservoir mask) group to achieve oxygen saturation > 90%.
• Based on a computerized randomization sequence, patients were further stratified and randomly assigned to hypercapnic (PaCO2 > 45 mm Hg) or nonhypercapnic (PaCO2 < 45 mm Hg) groups.
• An independent biostatistitian placed patients’ information in an opaque, sealed envelope.
• Subcutaneous morphine was given to reduce dyspnea scores by at least one point on the Borg scale (BS), and the total dose requirements over the first 48 hours were calculated.
• Arterial blood gas, vital signs, quantity of secretion, and dyspnea scores were measured at baseline and at one hour, 24 hours, and 48 hours.
• Mortality causes were recorded in the hospital and at three and six months after discharge.

• N = 200
• MEAN AGE = 71 years (NIV group), 70 years (oxygen group)
• MALES: 62%, FEMALES: 38%
• KEY DISEASE CHARACTERISTICS: Solid tumor cancers included lung, gastrointestinal, breast, head and neck, and esophageal. Respiratory failures included obstructive bronchus, carcinomatous, lymphangitis, and pleural effusion. Life expectancy was less than six months.
• OTHER KEY SAMPLE CHARACTERISTICS: Inclusion criteria were a P/F ratio of 1:250 and one of the following: dyspnea with a BS ≥ 4, signs of respiratory distress, or a respiratory rate ≥ 30. Exclusion criteria were reversible respiratory failure such as cardiogenic pulmonary edema or the exacerbation of chronic pulmonary disorders, treatment refusal, a weak cough reflex, agitation or uncooperative behavior, anatomical abnormalities with mask fitting, uncontrolled cardiac ischemia or arrhythmias, ≥ 2 organ failure, opioid use within past two weeks, adverse effects to opioids, substance misuse history, contraindication to morphine use, acute renal failure, and recent head injury.

• SITE: Multi-site  
• SETTING TYPE: Inpatient  
• LOCATION: Seven intensive care units and critical care units in Italy, Spain, and Taiwan

• PHASE OF CARE: End-of-life care
• APPLICATIONS: Palliative care

Multi-center, randomized, controlled trial

• McCabe Cyclomatic Complexity Index (MCCI) to record demographic information
• Simplified Acute Physiology Score II (SAPS) and Palliative Prognostic Index Score (PPIS) to determine mortality risk
• Kelly and Matthay Scale (KMS) to assess neurological status in patient with respiratory disease
• Modified Borg Scale (BS) to assess intensity of dyspnea
• Symptom Distress Scale (SDS) self-administered questionnaire to assess cancer-related symptoms

• In the NIV group, 11 patients (11%) dropped out of the study, but there was no attrition in the oxygen group.
• The NIV group had a statistically significant reduction in dyspnea levels at one hour, 24 hours, and 48 hours (BS = -0.58; 95% CI -0.92, -0.23; p = 0.0012). The greatest reduction was seen in the hypercapnic NIV group after the first hour (BS = -0.91; 95% CI -1.42, -0.46; p < 0.0001). 
• The total amount of morphine required over 48 hours was lower in the NIV group (SD = 37.3 mg) compared to the oxygen group (SD = 67.1mg) with a mean difference of -32.4 mg (95% CI -47.5, -17.4).
• In-hospital mortality was the same between the groups.
• The NIV hypercapnic group had better expected survival rates than the oxygen hypercapnic group.
• At discharge, symptom distress scores were statistically improved in the NIV group compared to the oxygen group (SD = 10 versus SD = 7.6; p = 0.001).

NIV was feasible and effective in decreasing dyspnea intensity and reducing morphine requirements in patients with end-stage cancer experiencing respiratory failure. However, additional studies validating these findings and determining the effects of NIV on survival and quality of life are needed.

• Risk of bias (no blinding)
• Key sample group differences that could influence results
• Findings not generalizable
• Intervention expensive, impractical, or training needs
• Subject withdrawals ≥ 10% 
• Other limitations/explanation: The benefit of performing a blinded study using a sham ventilation could have potentially caused harm to the patients in the oxygen group. Therefore, the researchers chose to maintain patient safety.
• The NIV group had an attrition bias. Also, the duration and timing of the NIV treatment was based on patients’ preferences and mask comfort, leading to a threat in internal validity. The NIV treatment may not be practical or cost effective in all palliative care centers because specialized training and equipment are needed. 

This study offers clinicians a treatment modality that can be used in adjunct with opioids to significantly reduce breathlessness in patients with end-stage cancer. Additional studies are needed to determine the specific patient population that would benefit the most from this treatment, its cost effectiveness, patient satisfaction, the adverse effects of NIV, and the survival rate.

DOI Link: doi: 10.1056/NEJM198102193040802

To evaluate protective isolation versus no isolation.

The authors evaluated single protective isolation (single-bed room and clean gowns, gloves, and masks for people entering room) versus standard care (two-bed room and reminder sign to wash hands).

Forty-three episodes of neutropenia occurred in adult patients.

• Inpatient
• Hematology-oncology unit

This was a randomized study.

No significant difference was found between isolated and nonisolated patients regarding the incidence of infection, time of onset of first infection, and days with fever.

Comprehensive, evidence-based guidelines were developed to assist healthcare professionals in providing optimal psychosocial care. The guidelines are multidisciplinary in focus, with recommendations applicable to diverse treatment settings.

Evidence was presented using levels I, II, III-1, III-2, III-3, and IV rating system with level I representing the gold standard.

 Clinically relevant recommendations supported by level I and II evidence about depression include the following.

• Referring high-risk patients to specialized psychological services to minimize the likelihood of developing significant distress (level I)
• Using a range of psychoeducational interventions to decrease distress (level I)
• Managing depression by incorporating a combination of supportive psychotherapy, cognitive and behavioral techniques, and pharmacotherapy (levels I, II)
• There is no evidence that any particular antidepressant is superior to another in the management of depression in people with cancer (level I).
• Other therapies that may improve depression are art, music, painting, reading, poetry, wellness programs, meditation, hypnosis, acupuncture, relaxation, exercise, prayer, and laughter. (levels I, II, III-3, IV).

The treatment of depression should incorporate psychotherapeutic interventions and the use of medication.

Evidence of the efficacy of antidepressant medication in treating depression in patients with cancer is clear.

No evidence suggests that any particular antidepressant is superior to another.

• The sedating properties of tricyclics may be beneficial to some patients, as may their potentiation and enhancement of opioid analgesia in those with pain.
• Their anticholinergic side effects may aggravate stomatitis, exacerbate constipation, and affect cardiac rhythm.
• Patients with cancer may respond to a lower dose of tricyclic antidepressants.
• Selective serotonin reuptake inhibitors have been demonstrated to be effective in treating depression in patients with cancer.
• The long half-life of fluoxetine makes it less desirable in patients with hepatic or renal dysfunction where sertraline or paroxetine is preferable.

The National Comprehensive Cancer Network is an alliance of 21 of the world’s leading cancer centers, working together to develop treatment guidelines for most cancers and dedicated to research that improves the quality, effectiveness, and efficiency of cancer care.

The NCCN Clinical Practice Guidelines in Oncology: Distress Management (Anxiety) are updated continually and are based upon evaluation of scientific data integrated with judgment by multidisciplinary experts. The NCCN guidelines development process relies heavily on structured feedback. One group of experts, develop the guidelines and another group of experts review them, which leads to revisions and modifications, reinitiating the feedback process.

NCCN Categories of Consensus: Category 1: There is uniform NCCN consensus, based on high-level evidence, that the recommendation is appropriate. Category 2A: There is uniform NCCN consensus, based on lower level evidence including clinical experience, that the recommendation is appropriate. Category 2B: There is no uniform NCCN consensus (but no major disagreement), based on lower-level evidence, including clinical experience, that the recommendation is appropriate. Category 3: There is a major NCCN disagreement that the recommendation is appropriate. All recommendations are category 2A unless otherwise indicated.

Screening of every patient with cancer for evidence of distress. Any patient with a score of > 4 of 10 for distress should be referred to a psychosocial service. Anxiety disorder is common in most patients with cancer. Evaluate patient’s safety. Evaluate patient’s decision-making capacity. Evaluate patient to determine anxiety related to: general medical condition; withdrawal from alcohol or narcotics, pain; generalized anxiety disorder; panic disorder; post-traumatic stress disorder; phobic disorder; or obsessive-compulsive disorder. The treatment recommended for anxiety (after eliminating medical causes) is psychotherapy with (or without) an anxiolytic with or without an antidepressant. If no response, re-evaluate medication (consider neuroleptics), psychotherapy, support, and education. If no response, evaluate for depression and other psychiatric comorbidity.

DOI Link: doi: 10.1007/s12185-015-1735-y

To assess the additional effects of aprepitant in combination with conventional 5HT3 blocker-based prophylaxis for chemotherapy-induced nausea and vomiting (CINV) during highly or moderately emetic chemotherapy for hematologic malignancies

Patients were divided into two arms. Patients in the conventional antiemetic therapy arm received 5HT3 receptor antagonists (RAs) alone (19 patients, control arm), and patients in the treatment group received 5HT3 RAs plus aprepitant (22 patients, aprepitant arm). The incidence of CINV and the use of rescue medications were analyzed and compared between the two groups over the total period of 10 days from the start of chemotherapy. Oral food intake also was appraised by patients and sorted into four levels: (1) not impaired, (2) slightly impaired, (3) moderately impaired to about half of the usual amount, or (4) severely impaired.

• N = 41  
• AGE = ≥ 20
• MALES: 65.85%, FEMALES: 34.14%
• KEY DISEASE CHARACTERISTICS: Hematologic malignancies 
• OTHER KEY SAMPLE CHARACTERISTICS: The eligible chemotherapies were limited to the following: (a) preparative regimens for autologous hematopoietic stem cell transplantation for multiple myeloma or malignant lymphoma, (b) platinum-containing regimens for resistant or refractory malignant lymphoma mainly consisting of etoposide, methylprednisolone, cytarabine, and cisplatin or its modified variant, which substitutes carboplatin for cisplatin, or (c) induction or consolidation therapies for acute leukemia, which contain either anthracyclines, high-dose methotrexate, or high-dose cytarabine. Patients with poor performance statuses or with an estimated life expectancy of less than three months were disqualified. Patients had to have sufficient cognitive capacity, adequate blood counts, no significant hepatic or renal dysfunctions at the start of chemotherapy. Patients who had had a previous history of aprepitant administration also were excluded.

• SITE: Single site    
• SETTING TYPE: Inpatient    
• LOCATION: The University of Tokyo Hospital

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

Randomized, controlled study

• Vomiting was measured daily by the number of vomiting episode the patient reported.
• Nausea was measured by Visual Analog Scale (VAS).
• The amount of oral food intake was recorded daily on days 1–10 of chemotherapy administration. 
• Rescue medication use was recorded by the physicians.

This study revealed the benefit of adding aprepitant to highly emetic chemotherapy regimens for various hematologic malignancies. Sufficient antiemetic effects were achieved without obvious adverse events, and additional aprepitant use is recommended for patients who received chemotherapy for a hematologic malignancy. The additional research of individual chemotherapies that specifically prefer antiemetic intensification with aprepitant is warranted.

• Small sample (< 100)
• Measurement/methods not well described

 

Aprepitant is a good option for nurses to recommend for patients receiving chemotherapy for hematologic malignancies. NK1s such as aprepitant are recommended in relevant guidelines.

DOI Link: doi: 10.1038/sj.bmt.1705846

To assess the use of palifermin in the prevention of oral mucositis (OM) and acute graft-versus-host disease (GVHD) after hematopoietic stem cell transplant (HSCT)

IV palifermin was administered at 60 mcg/kg for three consecutive days before and after conditioning therapy. These patients were compared to a retrospective control group.

• The study reported on a total of 106 patients, with 53 in the palifermin group and 53 in the control group.
• All patients received autologous or allogeneic transplantation with hematologic and nonhematologic diseases and had a Karnofsky score of 80 or higher.
• The palifermin group received transplantations between June 2005 and March 2006; the control group received transplantations between December 2000 and December 2005.
• Protocols were not indicated for either group.

This was a multicenter study conducted in Poland.

This was a retrospective control trial.

• The World Health Organization (WHO) Oral Toxicity Scale was used.
• Researchers recorded mucositis onset and incidence, use of analgesics, duration of total parenteral nutrition (TPN), incidence of febrile neutropenia, severe infections, and incidence of acute GVHD.

Incidence of all grades of mucositis was lower in the palifermin group (p < 0.001). Incidence of grades 3–4 was 13% in the palifermin group and 43% in the control group (p < 0.001). Mean duration was significantly lower (p < 0.001). No statistically significant differences in the onset of OM, duration of TPN, opioid use, incidence of febrile neutropenia, or severe infection were observed. No statistical significance in acute GVHD measures were observed, although the authors suggested that a decrease in acute GVHD may occur. Additional studies are necessary.

Adverse events (e.g., rash, pruritis, erythema, generalized edema, taste alteration, mouth or tongue thickness and discoloration, proteinuria) were mild in 15 patients, moderate in 15 patients, and severe but not life-threatening in 4 patients. No events caused discontinuation of palifermin.

• This was a retrospective trial.
• Expense was not addressed.
• The study used an IV formulation of palifermin.
• Ensuring all treatments were equal is not possible because of the study’s historical nature.

DOI Link: doi: 10.1177/1043454211408103

To evaluate the effectiveness of chlorhexidine mouthwash in children receiving chemotherapy

Databases searched were PubMed and ScienceDirect.

Search keywords were oral chlorhexidine, chemotherapy-induced mucositis/stomatitis, and pediatrics/children.

Studies were included in the review if they

• Were published between 1980 and January 1, 2010, in English.
• Involved human clinical trials in children between 0–18 years of age.
• Were prospective trials published in peer-reviewed journals.
• Used any antimicrobial agent for management of oral mucositis (OM).

Studies were excluded if they

• Included adults.
• Were meeting abstracts, letters, comments, case reports, or review articles.
• Were animal or in vitro, pharmacokinetic or pharmacodynamic, or retrospective and meta-analysis studies.

• A total of 13 references were retrieved, and five met the inclusion criteria. 
• All five studies assess chlorhexidine using a scale to assess OM. Three of them used the Modified Oral Assessment Guide 1–3 scale, one used the World Health Organization (WHO) 10-cm visual analog scale (VAS), and one study did not report the method of oral assessment (both groups were measured by presence of OM, bacteremia, and length of hospital stay).
• Antimicrobial treatment began before the start of OM in four studies and after the start of OM in one study.
• The duration of treatment for OM ranged from 6 weeks to 6 months.
• The five studies differed regarding types of patient, age groups, types of cancer treatment, concentrations of chlorhexidine rinse, how OM was assessed, and outcomes measured.

• A total of 175 patients were involved in the fix studies, with samples across studies ranging from 14–47.
• Two of the studies involved patients undergoing bone marrow transplant. All studies involved patients undergoing chemotherapy.
• All five studies used a control, usually a placebo mouthwash or sterile water.

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

• Three studies reported on the benefit of using chlorhexidine over benzydamine (Cheng & Chang, 2003; Cheng et al., 2004).
• One study showed benefit over placebo (Costa et al., 2003).
• One study showed no benefit using chlorhexidine over placebo (Raether et al., 1989).
• One study reported acceptance and tolerability of chlorhexidine (Cheng, 2004).

• Chlorhexidine may play a part in reducing OM during chemotherapy in pediatric patients.
• Further clinical trials are needed to examine more effective methods to prevent and manage OM.

• Most studies involved a small number of patients.
• The different scoring systems were not validated and were subjective.
• Studies were not blinded
• Studies differed in type of patient, age groups, type of cancer treatment, concentration of chlorhexidine rinse, how OM was assessed, and what outcomes were measured
• Literature evaluated was published over a 20-year period.

• Oral rinses for prevention or treatment of OM are a usually a good vehicle for treatment as long as they are easy to use, well tolerated, provide some quick relief of discomfort from OM, and are cost effective and accessible.
• The Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology recommends nonmedicated oral rinses for prevention of oral mucositis in adult patients with solid tumors of the head and neck and who are undergoing radiation therapy. 
• Oncology nurses are well positioned to educate children and their caregivers on proper use of oral rinses.

DOI Link: doi: 10.1111/nhs.12124

To test the feasibility and provide a preliminary evaluation of the effects of an exercise program for fatigue, sleep disturbance, mood, and symptoms in patients with cancer

Participants randomly were assigned to the treatment or control group. Patients in the control group received usual care, an educational booklet and DVD, and weekly telephone calls. Patients in the experimental group received initial one-on-one training sessions and were given exercise program kits containing written instructions, a pedometer, and an exercise log. Patients were to choose activities that provided low to moderate intensity exercise and perform these daily for at least 20 minutes. Participants also were asked to walk three to five days per week. Weekly phone calls to the experimental group were made to monitor participation and make adjustments to the walking prescription as needed. The program was planned for 12 weeks.

• N = 23
• MEAN AGE = 46.78 years (range = 31–59 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All patients had breast cancer (mostly stage II). Patients were recruited during chemotherapy given postoperatively.

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

• PHASE OF CARE: Active antitumor treatment

Randomized, controlled trial

• Piper Fatigue Scale (PFS)
• General Sleep Disturbance Scale (GSDS)
• Profile of Mood States–Short Form (POMS-SF)
• Memorial Symptom Assessment Scale (MSAS)

Patients in the experimental group demonstrated a nonsignificant improvement in fatigue (d = -0.48). There were no significant group by time effects for other measures. Data were not collected after week 10 because of loss of subject follow-up.

The findings of this study support the known effect of exercise on cancer-related fatigue; however, the small sample in this study limits the strength of these findings.

• Small sample (< 30)
• Small sample (< 100)
• Baseline sample/group differences of import
• Risk of bias (no blinding)
• Subject withdrawals ≥ 10%
• Other limitations/explanation: Patients in the control group reported higher fatigue levels at baseline.

This study provides minimal additional support for the benefits of exercise among women with breast cancer during active treatment. Exercise has been shown to be effective in reducing multiple symptoms, and nurses should encourage patients to be active.

DOI Link: doi: 10.1093/jjco/hyn010

To investigate the efficacy and safety of switching from oral morphine to oral oxycodone and to evaluate this regimen in patients with renal impairment

Patients were rotated from controlled-release (CR) oral morphine to oral oxycodone CR via a 3:2 ratio. Immediate-release (IR) oxycodone was used for breakthrough pain (BTP) at 1/6 of the 24-hour oxycodone dose. If pain intensity was rated as moderate to severe or if more than 3 rescue doses of IR oxycodone were administered in 24 hours, oxycodone was titrated upward. If untoward side effects were experienced, the oxycodone dose was titrated downward. Patients were deemed successful if pain control was adequate for 10 days. Pharmacokinetic evaluation for renal impairment was conducted on patients with adequate relief.

• The sample consisted of 25 patients.
• Mean age was 62.8 years (SD = 11.6 years).
• The sample was 24% female and 76% male.
• Cancer diagnoses included lung, breast, and pancreas.
• All patients were receiving morphine for cancer pain and were either having difficulty controlling pain with morphine or had intolerable side effects.

This study was a multisite, outpatient setting study conducted at 14 sites in Japan.

This was a multicenter, open label, dose-titration study.

• Pain control rate (i.e., the rate in which patients achieved stable and adequate pain control) was defined as CR oxycodone unchanged for 48 hours or more, slight or no pain intensity, fewer than two rescue doses in 24 hours, and tolerable side effects.
• A 0–100 mm pain intensity visual analog scale (VAS) was used with every administration. 
• Categorical acceptability was rated on a scale from 1 (very poor) to 5 (excellent).
• Safety was evaluated based on frequency, severity, seriousness, causality, and tolerability of adverse events.
• Serum creatinine and creatinine clearance were measured.

• The study yielded an adequate pain control rate of 84%, and time to adequate relief was 2.3 days.
• Pain intensity at study entry was 1.9 (moderate pain). Intensity significantly decreased by the end of the study (p < 0.0001).
• Average VAS went from 53.5 mm at study entry to 27.6 mm at study end (p < 0.0001).
• Acceptability was rated as very poor (12%) to poor (64%) at the beginning of the study. At end, acceptability was rated as very poor (8.3%), poor (16.7%), fair (45.8%), and good (29.2%). Mean acceptability was 2.1 at entry and 3.0 at end (p = 0.0004).
• Nausea was rated 2.3 with morphine and decreased to 0.4 with oxycodone (p = 0.0005), drowsiness went from 2.1 to 0.9 (p = 0.0313), vomiting went from 2.2 to 0.2, and constipation went from 2.2 to 1.6.
• M3G and M6G metabolites were increased at study initiation in patients with renal compromise; oxycodone metabolites were not increased in patients with renal compromise at the end of the study.

Rotation to oral oxycodone for patients who had inadequate pain control or significant adverse events with morphine was successful. Retention of oxycodone metabolites did not seem to exist in patients with renal compromise.

• The sample size was small, with fewer than 30 patients.
• The sample was not randomized, there was no control, and it was a convenience sample.
• Assessment for adverse events was subjective.

Oxycodone can be recommended as an alternative to morphine, and patients may experience fewer adverse events with oxycodone. Patients with renal compromise may benefit from oxycodone over morphine as morphine contributes to metabolite accumulation, leading to potential oversedation or adverse events.