To investigate the use of extra-orally applied near infrared phototherapy for the reduction of oral pain secondary to chemotherapy and radiation therapy induced mucositis in adult and pediatric HSCT patients.  

Eighty HSCT patients were divided into regular and low risk groups, and then into experimental and placebo groups. The experimental groups received gallium-aluminum-arsinide light emitting diode (LED) once daily, while the placebo group also received a similar appearing placebo treatment daily, beginning on day of HSCT (day 0) through day 14. The LED was applied extra-orally, by placing the light source in contact with the cheeks and anterior throat. The blinded evaluators examined the patients three times/week scoring their oral tissues, and patient reported pain assessments.

The sample was comprised of 80 patients age 3-74 years.

Males (%): 55 and Females (%): 45

Key Disease Characteristics: Aplastic anemia, neuroblastoma, AML, NHL, CLL, SLL, ALL, Hodkin’s disease, PNT, MES, Ewing's sarcoma, sickle cell anemia, CML, TC, HLH, WAS, MDS, osteoporosis, lymphoma, multiple myeloma, POEMS, amyloidosis

Other Key Sample Characteristics: All patients received conditioning therapy with melphalan.

Site: Multi-site

Setting Type: Not specified

Location: Children’s Hospital of Wisconsin, University of Alabama - Birmingham, The Children’s Hospital of Alabama

Phase of Care: Active treatment

Randomized, double-blinded, placebo-controlled

• WHO pain assessment scale
• NCICT GI Criteria for Adverse Events
• OMAS erythema or ulceration scale
• Patient diary form with questions concerning mouth pain -  ADULT - VAS (no pain and most severe pain possible) PEDIATRICS - Wong Baker FACES pain scale
• Patient diary using the same scales adapted to measure the impact on swallowing from no trouble to unable to swallow anything (including saliva)
• Patient report regarding eating normally; eat only soft solid foods; consume only liquids; or could not tolerate any food or liquids.
   

There were no significant differences in the WHO clinical examination scale between any of the groups. The other scales used also did not elicit significant differences.

Although it was not statistically significant, the data suggested a trend for the experimental groups to have general improvements in all of the scales.

Small sample <100

Groups were not split into children versus adults.

Inconclusive, would need much more research to demonstrate effectiveness. The positive note was that this treatment is applied extra-orally, making it more tolerable during periods of oral mucositis. This treatment would require education for the healthcare team as well as added cost for the use of the technology.

PHASE OF CARE: Active antitumor treatment
 
APPLICATIONS: Palliative care

Per the authors, evidence exists to support olanzapine in highly emetogenic regimens. The Navari (2011) trial was the strongest study to support the use of olanzapine. Toxicity in all included trials demonstrated little side effects. Only one trial described sleepiness during chemotherapy. Olanzapine is a safe and more costly option to use instead of NK-1 antagonists. When used with other antiemetics such as metoclopramide there is a role in prevention, and as a single agent it shows efficacy in delayed CINV as well.

There were only three studies in each group. Only the Shumway trial was double-blinded, but it was a small trial. All the breakthrough trials were by the same investigator and included less than 110 patients.

Olanzapine may have a role in preventing CINV and delayed CINV but there is still limited research. The most recent trial for delayed CINV is a small trial but is double-blinded. Further research is indicated.

To evaluate efficacy and effective doses of a dimethyl sulfoxide (DMSO) sodium bicarbonate combination for refractory pain in patients with cancer

Participants received 8 infusion cycles of 20–60 ml of DMSO mixed with 1.4% of NaHCO3 daily for 10 days with 2 days off between cycles. Data were recorded at baseline, and at 3, 10, 20, 30, 60, and 96 days. Patients were allowed to take any medication, supplements, or herbal preparations as usual for them. The DMSO concentration was increased incrementally until pain was completely under control.

• The study reported on 26 patients.
• The mean age was 56.8 years, with a range of 17–72 years.
• The sample was 38% female and 62% male.
• All patients had life expectancies of six months or less.
• A variety of cancer types were included, with primary liver, lung, and colorectal cancers the most prevalent.

The study was conducted at a single-site, inpatient setting in Hanoi, Vietnam.

This was an open label, prospective trial.

Patients used a verbal pain scale ranging from 0 (no pain) to 4 (extreme pain).

After 2 cycles, 11 (43%) patients achieved 20% or more reduction in pain and were discharged from the hospital to outpatient therapy. After 3 cycles, an additional 23% achieved this level of pain control. All but 4 patients achieved pain control at this level by day 96. By day 96, 83% of patients used less pain medication. No major negative effects occurred related to the infusion solution. The most frequent side effects were headache and chills during and after treatment. These effects resolved within 2 hours. The proportion of patients with other symptoms also was reported to decline over the course of the study.

This preliminary information suggests that this DMSO and NaHCO3 infusion can have a positive benefit for patients in the relief of refractory pain and is not associated with severe adverse effects.

• The sample size was small, with fewer than 30 patients.
• This was an open-label design with no control or comparison group.
• The single measurement method for pain did not have established reliability and is a rather gross measure to use in defining complete pain control.
• The authors reported a decline in the prevalence of other symptoms, but they did not provide information on how these were measured or how symptom absence was determined.

Findings suggest that this DMSO infusion may be a safe alternative for pain control in terminal patients with severe pain that is not otherwise well controlled. However, the study does not provide sufficient support for this intervention. The positive findings here suggest that further well-designed research on DMSO infusion is warranted.

To investigate the effectiveness of dance movement therapy on treatment-related symptoms

The program consisted of six 1.5-hour sessions of dance movement therapy twice weekly for three weeks during radiotherapy. Therapy involved use of stretching, movement to exercise upper extremities, improvisational dance, and expressive movement. Participants were encouraged to share experience and communicate and to relate movement to personal experiences of breast cancer and treatment. Patients were randomized to the intervention or a wait-list control group.

• N = 139 (ITT analysis), 127 with complete data   
• MEAN AGE = 49 years
• FEMALES: 100%
• CURRENT TREATMENT: Combination radiation and chemotherapy
• KEY DISEASE CHARACTERISTICS: All had breast cancer, and about 80% were also receiving chemotherapy
• OTHER KEY SAMPLE CHARACTERISTICS: Over half were married, and 65% had education at secondary level or below.

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: Hong Kong

• PHASE OF CARE: Active antitumor treatment

• Single-blind randomized controlled trial

• Perceived Stress Scale (PSS)
• Brief Pain Inventory (BPI)
• Brief Fatigue Inventory (BFI)
• Hospital Anxiety and Depression Scale (HADS)

All patients showed decline in fatigue scores over time with no difference between groups. Sleep disturbance declined in the study group and increased slightly in the control group, but differences were not significant. Anxiety and depression remained stable in both groups. Pain severity and pain interference declined in the dance group and increase in the control group (p < 0.05). The size of effect for pain was moderate (d = 0.35). Perceived stress declined in the dance group compared to controls (p < 0.05). The program had a high completion rate.

Participation in this group dance movement therapy was associated with decline in pain severity and interference.

• Risk of bias (no appropriate attentional control condition)
• There is no description of the type of pain, use of any pain medications, or other interventions in either group. The group interaction may have had as much to do with any reduction in symptoms as the actual dance activities.

The dance movement therapy program used here combined rhythmic and expressive movement with group sharing and support. The contribution of each of these components cannot be differentiated, but results showed positive benefits in terms of pain and perceived stress. There were a number of study limitations; however, the program completion rate was high, and there were no adverse effects, suggesting that this type of intervention can be practical to provide during active radiotherapy treatment.

To evaluate the efficacy of IV ramosetron plus dexamethasone compared to granisetron plus dexamethasone for the prevention of acute chemotherapy-induced nausea and vomiting (CINV)

Subjects were randomized to receive 0.3 mg ramosetron plus 20 mg dexamethasone or 3 mg granisetron plus 20 mg dexamethasone on day 1 prior to chemotherapy. Patients were evaluated over a 24-hour period. All vomiting episodes were recorded by the patient. Every 6 hours, the degree of nausea was evaluated.

• The sample consisted of 285 participants.
• The mean age of participants was 51 years with a range of 22–74.
• The sample was 60.8% female and 38.2% male.
• Diagnoses were breast (43.2%) and lung (29.1%), as well as nasopharynx, mouth, rectum, liver, bladder, stomach, esophagus, testis, brain, and other.
• All patients were receiving emetogenic chemotherapy including cisplatin, doxorubicin, epirubicin, or oxaliplatin.
• Patients were not eligible if they had symptoms of vomiting for at least one week before study entry.

The study was conducted at multiple sites in Taiwan.

All patients were in active treatment.

This was a randomized trial (double-blind), parallel group trial.

Complete response (CR) was defined as no vomiting and no rescue medication. The date, time, and number of episodes of vomiting or retching were recorded. Patients rated their levels of nausea using a 10-cm visual analog scale (VAS) tool. Total control was defined as no vomiting and nausea rating of less than 0.5 cm on the VAS tool. A proportion of subjects received rescue drugs.

• No difference was found between the ramosetron plus dexamethasone group and the granisetron plus dexamethasone in CR rates.
• No statistically significant differences were found in the proportions of patients with vomiting, nausea on the VAS scale, or rescue medication.
• No differences were found in drug-related adverse events between the two treatment arms.
• The most frequent adverse event reported was hiccups in both groups.
• Overall, 77.4% of patients receiving ramosetron and 82% of patients receiving granisetron achieved CR.

Ramosetron plus dexamethasone regimen was found to be equivalent to granisetron plus dexamethasone in CR rate during the acute phase.

• Patients receiving both highly and moderately emetogenic chemotherapy were combined, with no subgroup analysis for different levels of emetogenicity.
• Patient compliance with diary recording was not discussed

Ramosetron plus dexamethasone regimen was found to be as effective as granisetron plus dexamethasone in the management of CINV during the acute phase, suggesting that ramosetron could be used as an alternative to other 5-HT₃ receptor antagonists in highly and moderately emetogenic chemotherapy.

To examine the effects of administration of synthetic ghrelin on appetite and oral intake in patients with advanced esophageal cancer during chemotherapy

Patients were randomized to receive either ghrelin at 3 µg/kg over 30 minutes twice daily or placebo for seven consecutive days (days 1–7 of therapy) intravenously. All patients also received the same protocol of IV fluid of 3 L/day from days 1–3 and 2 L/day from days 4–7. Appetite was scored prior to each meal. A registered dietitian determined caloric intake by measuring the weight of each dish before and after every meal.

• The study reported on a final sample of 40 patients.
• Mean patient age was 63.4 years.
• The sample was 87.5% male and 12.5% female.
• All patients had stage II or higher esophageal disease. All were receiving cisplatin-based chemotherapy.

• Single site 
• Inpatient setting
• Japan

Patients were undergoing active antitumor treatment.

The study was a placebo-controlled randomized controlled trial.

• Appetite visual analog scale (VAS)
• Caloric intake
• Rapid turnover protein levels: prealbumin, transferrin
• Common Terminology Criteria for Adverse Events

Dietary intake declined after cisplatin administration to the lowest levels on days 5–7. It took another 4–7 days for oral intake to recover and enable discharge from the hospital. The decline in dietary intake was less in the ghrelin group (p = 0.0027). On day 7, intake with ghrelin was 26.7 kcal/kg/day compared to 23.1 kcal/kg/day for those receiving placebo. Prealbumin was higher in those on ghrelin (p = 0.042), and transferrin was higher with ghrelin (p = 0.037) compared to those levels in the placebo group. The severity grades of anorexia and nausea were lower with ghrelin (< 0.02).

Findings suggest that administration of ghrelin during cisplatin-based chemotherapy was effective in reducing anorexia and maintaining caloric intake compared to placebo.

• The study had a small sample size, with less than 100 participants.
• Lack of blinding had an associated risk of bias.
• Unintended interventions or applicable interventions were not described that would influence results.
• The intervention was expensive, impractical, or required training.
• The use of antiemetics during treatment was not described, so it is unclear whether there were differences between groups that could have affected outcomes.
• Although findings were statistically significant, the actual difference in caloric intake appears to be fairly small.
• The sample included only patients who had no previous chemotherapy, and physicians had discretion to exclude patients based on no particular criteria. It is unclear whether this could have produced sample bias. 
• This protocol would only be feasible in an inpatient setting.

Findings suggest that ghrelin as administered in this study may be beneficial to preserve appetite and nutritional intake during chemotherapy.  As done here, ghrelin and fluid administration would only be practical in an inpatient setting.

The hypothesis was that micafungin (150 mg) is a safe and effective alternative to fluconazole (400 mg) for the use of antifungal prophylaxis during neutropenia.

Patients were randomly assigned to receive either micafungin or fluconazole treatment using a 1:1 schedule.  Randomization was stratified according to the risk or transplant-related mortality.  High risk included acute leukemia in relapse or in complete remission for at least the third time, chronic myelogenous leukemia other than the first chronic phase, Hodgkin lymphoma or non-Hodgkin lymphoma in relapse or greater than or equal to the second complete or partial remission, myelodysplastic syndrome, or myeloproliferative syndrome.  Low risk included all factors not classified as high risk and any type of transplant (i.e., autologous, allogeneic using peripheral blood stem cells or bone marrow, or allogeneic using cord blood).  Groups received either 150 mg of micafungin or 400 mg of fluconazole daily by infusion until the earliest of: (1) absolute neutrophil count (ANC) of 500 cells/mm³ or greater, (2) 42 days after hematopoietic stem cell transplantation (HSCT), (3) development of proven, probable, or suspected invasive fungal infection, (4) development of unacceptable drug toxicity, or (5) other reason for withdrawal or discontinuation of treatment.  Antifungals were given within 48 hours of initiation of the transplant conditioning treatment.

• One hundred four patients were evaluable (52 patients in each arm).  
• Mean age was 46.5 years (range 16–67) in the micafungin arm and 47.3 years (range 18–65) in the fluconazole arm.
• In the micafungin arm, 64% of patients were male and 36% were female.  In the fluconazole arm, 68% of patients were male and 32% were female.
• Key disease characteristics were malignant lymphoma (46% in the micafungin arm, 44% in the fluconazole arm), multiple myeloma (18% in the micafungin arm, 26% in the fluconazole arm), acute myeloid leukemia (AML) (14% in the micafungin arm, 12% in the fluconazole arm); myelodysplastic syndrome (MDS) (10% in the micafungin arm, 8% in the fluconazole arm); acute lymphoblastic leukemia (ALL) (6% in both arms), and other hematologic malignancy/nonmalignant disease (6% in the micafungin arm, 4% in the fluconazole arm).  
• Transplant type included autologous HSCT in 48% of patients in both arms and allogeneic HSCT in 52% of patients in both arms.  Peripheral blood was used in all autologous HSCTs, allogeneic bone marrow or peripheral blood was used in 38% of patients in the micafungin arm and 44% in the fluconazole arm, and cord blood was used in 14% of patients in the micafungin arm and 8% in the fluconazole arm.

• Mutli-site  
• Inpatient
• Patients were hospitalized at the hematology departments of six study sites in Japan.

Patients were undergoing the active treatment phase of care.

This was a prospective, randomized, open-label comparative trial.

• Treatment success was defined as an absence of proven, probable, or suspected systemic fungal infection through a four-week period.     
• Definitions of the Fungal Infections Cooperative Group of the Suropena Organization for Research and Treatment of Cancer, National Institute of Allergy and Infectious Diseases Mycoses Study Group were used.
   

Neutrophil recovery was seen in an average of 13.7 days in both arms.  Graft-versus-host disease was present in 24% of patients in the micafungin arm and 30% in the fluconazole arm.  Overall treatment success, defined as the absence of proven, probable, or suspected systemic fungal infection through the end of prophylaxis therapy and as the absence of a proven or probable systemic fungal infection through the end of the four-week posttreatment period, was comparable in both arms, with 94% in the micafungin arm and 88% in the fluconazole arm.  This was not a significant difference.

The study showed that another class of medications, the echinocandins, can be effective in preventing fungal infections.  Its effectiveness is comparable to that of fluconazole, which is considered the gold standard for antifungal prophylaxis.  Neither drug had significant side effects, although the incidence was slightly higher with the use of micafungin.

This was an open-label study and was not powered to measure success rate differences.

Patients should be educated regarding the use, effectiveness, side effects of the medications, and need for continued antifungal prophylaxis based on risk.

To determine the effectiveness of a care bundle completed by patients with esophageal cancer before surgery to reduce the risk of postoperative pneumonia

• N = 240  
• MEDIAN AGE = 64 years (range = 36–86 years)
• MALES: 83.3%, FEMALES: 16.7%
• KEY DISEASE CHARACTERISTICS: Esophageal cancer
• OTHER KEY SAMPLE CHARACTERISTICS: The comparison groups were significantly different based types of surgery. The care bundle group was 65.4% thoracotomy and 34.6% thoracoscopic versus the non-care bundle group, which was 96.7% thoracotomy and 3.3% thoracoscopic.

• SITE: Single site    
• SETTING TYPE: Multiple settings  
• LOCATION: Japan

• PHASE OF CARE: Active antitumor treatment

Retrospective, case-controlled study comparing two groups of patients, each from a different time period in the past.

The definition of postoperative pneumonia was based on the Centers for Disease Control and Prevention criteria. The detection of postoperative pneumonia was based on bacteria collected from a bronchoscope within 30 days of surgery. An analysis between groups was completed using logistic regression.

Completing daily care bundle activities before surgery for esophageal cancer may lower the risk of postoperative pneumonia. The study design and underadherence to care bundle activities limit stronger conclusions. However, most care bundle activities were inexpensive with little risk to patients, so the use of this intervention may still be warranted.

• Small sample (< 30): Not for study as a whole, but for the intervention group
• Baseline sample/group differences of import: Significant difference in surgical approach (p < 0.001) and operative time (p = 0.002) between the comparison groups; variation in adherence to care bundles
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Other limitations/explanation: Although compliance rates with the care bundle activities reflect real-world applications, it makes the conclusions based on care bundle activities difficult to discern. Also, it was unclear how many days preoperatively a patient should complete the care bundle activities.

Preoperative nursing interventions and patient education may influence postoperative health outcomes. Nurses can promote smoking cessation, deep breathing, breathing exercises, oral care, and adherence to nutritional guidelines before surgery for esophageal cancer as a potential strategy to decrease the risk of postoperative pneumonia.

To examine the feasibility and effectiveness of problem-solving therapy for psychological distress among patients with early-stage breast cancer

The problem-solving therapy involved five weekly sessions aimed at assessing problems, setting goals, generating solutions, choosing a solution, and implementing the solution and evaluating results. The therapy included a manual and worksheet for patients to use. Authors collected self-report data prior to the intervention, after the final sessions, and three months after the final sessions.

• Mean patient age was 50.21 years (SD = 11.09 years).
• The sample was 100% female.
• The majority of participants had stage II disease. All had had prior surgery; 89% were on hormone therapy.
• Of all participants, 43% were employed full- or part-time, 79% were married, and 21% had a college education.

• Single site
• Outpatient setting
• Japan

Patients were undergoing active antitumor treatment.

A pre/post-test design was used.

• Two-item 11-point Likert-type distress scale
• Hospital Anxiety and Depression Scale (HADS), Japanese version
• Scale that measured self-efficacy of patients with advanced cancer
• Brief Cancer-Related Worry Inventory
• European Organization for Research and Treatment Cancer Core Quality-of-Life Questionnaire (QLC-C30), Japanese version

Four patients dropped out of the study after starting treatment. Analysis showed a significant effect of time on anxiety and depression scores (p < 0.01).  Over time scores for global health status, physical functioning, emotional functioning, and role functioning improved significantly.

The study shows that symptoms of anxiety and depression and some aspects of quality of life improved over time. The effect of the intervention cannot be evaluated from these study results. Though authors state that the intervention was feasible, the fact that 17% of the initial sample did not complete the study suggests that the intervention was not of interest to a substantial proportion of the patients.

• The study had a small sample size, with fewer than 30 participants.
• The study had risks of bias due to the lack of a control group, blinding, and random assignment.

Study results are insufficient to allow evaluation of the acceptability and efficacy of the problem-solving intervention.

To assess the safety and efficacy of aprepitant for chemotherapy-induced nausea and vomiting (CINV) prophylaxis with highly emetogenic cheomtherapy (HEC) or moderately emetogenic chemotherapy (MEC) regimens

Patients received 125 mg aprepitant on day 1 and 80 mg along with palonosetron and dexamethasone

• N = 75   
• AGE RANGE = 18-71 years
• MALES: 10.3%, FEMALES: 89.7%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Multiple tumor types 
• OTHER KEY SAMPLE CHARACTERISTICS: Sixty percent were receiving HEC therapy.

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

PHASE OF CARE: Active antitumor treatment

Open-label, prospective, observational

• Complete response (CR) defined as no emesis and no use of rescue medicatiton
• Common Terminology Criteria for Adverse Events (CTCAE), version 4

For all regimens, CR rates were 96.8%, 93.7%, and 92% for acute, delayed, and overall phases. Nine percent reported side effects; the most common was hiccoughs.

Triple drug antiemetic prophylaxis was effective to manage CINV in most patients.

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

This study adds to the substantial body of evidence for the efficacy of triple drug antiemetic regimens for the prevention of CINV.