To assess the effectiveness and feasibility of implementing an oral cryotherapy plus oral care protocol to reduce oral mucositis (OM) severity in patients with multiple myeloma undergoing autologous stem cell transplant (ASCT)

Participants were randomized into an oral cryotherapy study group or a standard oral care control group. Patients in the oral cryotherapy study group received verbal and written instructions on oral cryotherapy plus an oral care protocol in place at the study site. Oral cryotherapy consisted of sucking on ice chips five minutes before, during, and after melphalan administration for a total of 60 minutes. The standard oral care protocol included education regarding oral self care, brushing with Toothette® brushes dipped in sodium bicarbonate, mouth rinsing with sodium bicarbonate mouthwash, and applying moisturizer to lips or the oral cavity. Patients were permitted to floss until their platelet counts fell below 50,000. Patients in the standard oral care control group received only the instructions on the oral care protocol (no cryotherapy). Outcomes were evaluated on days 3, 6, 9, and 12 after stem cell rescue. A research assistant who was blinded to group assignment assessed each participant and recorded the results of the assessment on data collection forms.

• The study reported on 46 patients aged 18 years and older.
• Patients' ages ranged from 43–72 years.
• The sample was 58% male and 42% female.
• Patients had been diagnosed with multiple myeloma and were undergoing ASCT. They were scheduled to receive 200 mg/m² high-dose melphalan. Additionally, they were scheduled to receive growth factors. They had no preexisting oral disease.
• Statistically significant differences existed between the study group and the control group related to age and education.

The study was conducted at a single-site, inpatient setting in Ontario, Canada.

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

This was a prospective, pilot, randomized control trial with repeated measures.

• The World Health Organization (WHO) mucositis grading scale was used.
• Pain was assessed using a 100-mm visual analog scale.
• Opioid use was assessed quantiatively by converting into morphine-equivalent units.
• A nutritional assessment form was used to record functional intake of food and fluids.
• Lengths of stay were recorded from medical records.
• An oral therapy questionnaire was used to assess the tolerability of cryotherapy.

• All participants were free of OM symptoms on days -1 and +3. Signs and symptoms of OM were observed on day +6 and were most pronounced on day +9. Symptoms of OM began to resolve on day +12.
• The overall mean severity scores for OM on the WHO scale were statistically significant (0.43 to 1.14, p < 0.001) on days +9 and +12 (p = 0.03), both in favor of the study group. On day +6, the statistically significant difference (p = 0.02) favored the control group.
• Pain scores were lower for the study group (p  < 0.01), and more participants in the control group used opioid analgesics than in the experimental group (41% versus 13%).
• No significant differences were found related to functional intake of food and fluids.
• The study group experienced a one-day decrease in length of stay, but this was not statistically significant.
• Cryotherapy was somewhat or well tolerated by 87% of patients. Side effects of teeth sensitivity and chills were reported by 17.4% of participants in the study group.

Cryotherapy in addition to an oral care protocol (as described above) is likely to be beneficial in reducing the severity of OM as well as decreasing pain and the need for opioid analgesics. In terms of lengths of stay, cryotherapy offered a clinical benefit, although not statistically significant.

• The sample size was small with fewer than 100 patients.
• Some data collection required patients to self-report.
• The study observed only adult patients diagnosed with multiple myeloma and undergoing stem cell tranplant.
• The study was limited in that the only OM-causing agent was melphalan.
• The study was not blinded.

Cryotherapy is inexpensive, and the protocol is relatively simple. In conjunction with an oral care protocol, this is a reasonable approach to take. A larger trial would be helpful.

To evaluate the effect of low-dose methadone as the primary long-acting opioid in a hospice setting

Two hundred and forty charts of patients who were admitted to a community-based hospice setting from July 1, 2011–April 1,2012 were reviewed. Patients received short-acting doses of opiates equivalent to 5 mg every four hours as needed. Once two or more doses were needed, 2.5 mg methadone was initiated and titrated up by 2.5 mg increments every four to seven days as needed. Median dose of methadone was 5 mg daily, but max dose was 15 mg. Haloperidol was the most commonly prescribed adjuvant nonopoid medication, with a median dose of 3 mg daily. Pain was assessed during each nursing visit on a 0–10 scale and every time the short-acting opiate dose was used more than two times a day. If patients were on long-acting opiates and their life expectancy was greater than a week, they were offered conversion to methadone. Nonopioid agents were used for pain and other symptoms, with Haldol^® being the primary agent for the purpose of NMDA inhibition. If patients were unresponsive, their pain was assessed by their caregiver.

• N = 103 patients with cancer (236 total patients with and without cancer) 
• MEAN AGE = 75 years in patients with cancer (81 years in patients with and without cancer)
• MALES: 33% in patients with cancer (39% in patients with and without cancer), FEMALES: 67% in patients with cancer (61% in patients with and without cancer)
• KEY DISEASE CHARACTERISTICS: 44% had cancer diagnoses, 56% had noncancer diagnoses
• OTHER KEY SAMPLE CHARACTERISTICS: Evaluated patients admitted for hospice care only

• SITE: Single site 
• SETTING TYPE: Other 
• LOCATION: Community-based hospice service

• PHASE OF CARE: End-of-life care
• APPLICATIONS: Elder care, palliative care

A retrospective review of electronic records in those admitted to a community-based hospice service from July 1, 2011–April 1, 2012. Information was reviewed until patients were discharged from hospice or until April 30, 2012.

• Demographics, medication regimens, and pains scores were extracted from electronic medical records.
• Descriptive statistics were used to summarize results.
• Median and peak pain scores (on a scale of 0–10) were recorded.
• Pain scores greater than 4 were considered moderate to severe.

Two-thirds of patients never reported a score greater than 3 on a 0–10 numeric scale. The median reported score was 2 with a peak pain score of 3, with similar reports looking at cancer versus noncancer groups separately.

Methadone provided good pain control for the majority of patients. Methadone could be used with Haldol in pain control, particularly in circumstances in which patients experience a paradoxical reaction (caused by desensitization because of tolerance) and sensitization of the NMDA pathway responding to opioid receptor stimulation. More controlled trials will need to be conducted to consider this as a first-line treatment for management of pain.

• Baseline sample/group differences of import
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Risk of bias (no appropriate attentional control condition)
• Unintended interventions or applicable interventions not described that would influence results
• Key sample group differences that could influence results
• Measurement validity/reliability questionable
• Findings not generalizable
• Other limitations/explanation: Other agents used in symptom management could have an effect on reporting or perception of pain. Pain assessment not was not rigorous in this study. This was a retrospective, observational study with no control. This study is not generalizable. Pain was not assessed at baseline for more than half of the patients, causing inability to assess short-term effect.

Methadone is low-cost. Education to providers would be needed because the use of methadone may not be a common practice and conversion may be difficult. Risk of constipation is lower with the use of methadone, which may improve quality of life for those suffering from pain and perhaps lower overall pain. Working with high doses of methadone comes with large risk, so careful consideration should be used when prescribing.

STUDY PURPOSE: To evaluate the effectiveness of acupuncture in treating hot flashes in women with breast cancer

TYPE OF STUDY: Systematic review and meta-analysis

• FINAL NUMBER STUDIES INCLUDED = 12
• TOTAL PATIENTS INCLUDED IN REVIEW = Did not report
• SAMPLE RANGE ACROSS STUDIES: 10–84 patients
• KEY SAMPLE CHARACTERISTICS: Women with breast cancer receiving acupuncture for hot flashes

PHASE OF CARE: Transition phase after active treatment
 
APPLICATIONS: Elder care

The meta-analysis without any subgroup or moderator did not support favorable effects of acupuncture in reducing the frequency of hot flashes after the intervention in women with breast cancer.

This meta-analysis did not conclude that data support the effectiveness of using acupuncture therapy to decrease the frequency of hot flashes in women with breast cancer. Limitations of the study included heterogeneous studies with a limited number of patients. The author noted the poor quality of the primary data.

• Limited number of studies included
• Mostly low quality/high risk of bias studies
• High heterogeneity
• Low sample sizes
• Patient selection was not clearly defined to describe the full characteristics of the patient selection.
• Did not document if patients were on hormonal therapy or if they were experiencing hot flashes
• Total number of subjects not reported

The findings did not support the therapeutic use of acupuncture to decrease the frequency of hot flashes in women with breast cancer.

To assess the efficacy of continuous IV infusion of ketamine in patients suffering from opiate-refractory cancer pain admitted to palliative care units

Patients were computer randomized to either IV morphine plus ketamine or morphine plus placebo. Morphine could be titrated by 50% once daily. Evaluations were performed at baseline, 2 hours, 24 hours, and 48 hours after initiation of infusion. Ketamine was given at continuous infusion of 0.5mg/kg per day and increased to 1mg/kg per day if pain score did not improve after 24 hours.

• The sample consisted of 20 patients (11 experimental and 9 control) with a mean age of 60.3 years.
• The sample was 70% male and 30% female.
• Key disease characteristics were  not included.

This was a multisite study conducted in France.

• Patients were in the end-of-life phase of care.
• The study has clinical applicability to end of life and palliative care.

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

• Pain was rated using a Numeric Pain Intensity Scale from 0–10.
• The Edmonton Symptom Assessment Scale and Patient Treatment Satisfaction Scale were used.
• Daily morphine dose was recorded.
• The Epworth Sleepiness Scale (ESS) was used to record daytime sleepiness.

Pain did not significantly differ between the two groups. No significant differences were found in morphine changes, ESS scores, or satisfaction scores between the two groups.

The combination of morphine and ketamine did not improve pain or decrease opioid requirements.

• The sample size was small, with fewer than 30 patients.
• Ketamine doses were not titrated, and only one dose was trialed. A dose finding trial is needed.

Although ketamine did not improve pain scores in patients with opiate refractory pain, further studies are needed because of study limitations.

To clarify the efficacy of probiotics in children and adults

• Databases searched were PubMed, Web of Science, Scopus, and the Cochrane Database.
• Search keywords were probiotics and diarrhea.
• Studies were included in the review if they were randomized clinical trials (RCTs) and involved children.
• Studies were excluded if they were uncontrolled trials or the results did not address study goals.

• A total of 1,228 references were retrieved.
• The Jadad scale quality rating was used to evaluate the literature.

• The final review involved 20 studies with total sample of 3,867 patients. Sample sizes ranged from 69–913 patients.
• Most trials involved children. Two studies were included regarding radiation-induced diarrhea and one trial involved chemotherapy-related diarrhea. These studies were not included in the meta-analysis.

The effect size for probiotics compared to placebo in 19 trials related to duration of diarrhea was -0.67 (95% confidence interval [CI] = -0.95–0.38) in favor of probiotics. Heterogeneity was statistically significant. Findings included evaluation of duration of diarrhea, hours of fever, duration of hospitalization, duration of vomiting, and number of stools per day. Authors reviewed subsets of information for children, adults, cases of amebiasis and clostridium difficile, HIV, and radiation or chemotherapy.

Taken as a whole, authors concluded insufficient evidence exists for the efficacy of probiotics for different types of diarrhea in children or adults.

• Very few of the trials were relevant to oncology.
• Trials involved both children and adults. However, only the trials involving children were included in the meta-analysis. 
• High heterogeneity existed among the studies. 
• Variations in specific probiotics may have influenced results.
• The authors noted the need for agreement among researchers in defining measurements including what constitutes the end of diarrhea.

These findings did not provide strong support for the use of probiotics for prevention or management of diarrhea in patients receiving radiation or chemotherapy. Overall evidence in all groups was limited by a number of factors. The specific type, dosages, and timing of probiotic use varied.

To evaluate the efficacy of aprepitant in addition to standard antiemetic therapy with ondansetron and methylprednisolone in the prevention of chemotherapy-induced nausea and vomiting (CINV) caused by high-dose melphalan given as part of conditioning for allogeneic ​hematopoietic stem cell transplantation (HSCT)

• N = 60 (20 in the treatment arm, 40 in the control arm)
• MEDIAN AGE = 47 years (control), 52 years (treatment)
• MALES: 50% (control); 52.5% (treatment), FEMALES: 50% (control), 47.5% (treatment)
• KEY DISEASE CHARACTERISTICS: Lymphoma and multiple myeloma
• OTHER KEY SAMPLE CHARACTERISTICS: Patients received fludarabine and high-dose melphalan conditioning were included. Patients receiving TBI for graft-versus-host disease prophylaxis also were enrolled.

• SITE: Single site    
• SETTING TYPE: Inpatient    
• LOCATION: Tokyo, Japan

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

Retrospective, single-center analysis

Medical records during the period were analyzed to extract data about CINV and food information. Adverse events were monitored during the observation period, and there were no statistically significant differences in the incidence of grade 2 or greater adverse events between the two groups.

Aprepitant was well tolerated and positively affected the rates of delayed vomiting in this population. The ability to consume food more quickly after the conditioning regimen was improved with aprepitant.

• Small sample (< 100)
• Risk of bias (no random assignment)
• Selective outcomes reporting
• Measurement validity/reliability questionable
• Other limitations/explanation: Retrospective design instead of a prospective, randomized, controlled trial

This retrospective study did not indicate how the data were categorized from the records. There was no specific information regarding the rescue antiemetics used, and the rescue medications were chosen by the physicians. This impact on CINV was not discussed in the manuscript. The results are intriguing and demonstrate the safety of adding aprepitant, but a prospective, randomized, controlled trial will be needed to change clinical practice.

To assess the usefulness of prophylactic professional oral health (POHC) care done by dentists and dental hygienists for preventing mucositis in patients undergoing chemotherapy

• N = 26  
• MEDIAN AGE = 58 (+/– 9.8) years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Patients with breast cancer receiving chemotherapy
• OTHER KEY SAMPLE CHARACTERISTICS: No significant differences existed between the two groups with regard to age, BMI, or number of teeth.

• SITE: Single site    
• SETTING TYPE: Outpatient    
• LOCATION: Department of Surgery at Tokyo Dental College, Ichikawa General Hospital

• PHASE OF CARE: Active antitumor treatment

• Randomized controlled trial

• National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (NCI-CTCAE)
• Eiler’s Oral Assessment Guide (OAG)
• Evaluation of oral hygiene using plaque control records (PCR)
• Evaluation of dry mouth and oral moisture using the Saxon test and oral moisture checking device (MUCUS) 
• Gustatory measurements using an electrogustometer

Further studies are needed to investigate the addition of professional oral care along with self-care. In this study, oral mucositis was not improved or made worse by professional oral care. There is a definite role for better education regarding self-care and adherence to self-care with oral hygiene. Patients need to understand how their oral care can affect the side effects they may experience from the medication.

• Small sample (< 30)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Risk of bias (sample characteristics)
• Findings not generalizable
• Other limitations/explanation: Single gender study and single diagnosis

To evaluate the efficacy and safety of single-dose fosaprepitant in combination with IV granisetron and dexamethasone to prevent chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy (HEC) containing cisplatin at 70 mg/m² or higher

Patients receiving high-dose cisplatin were randomized to one of two groups (fosaprepitant or placebo). On day 1, one hour before antineoplastic treatment, both groups received IV granisetron 40 µg/kg and an IV infusion over 20-30 minutes of either fosaprepitant 150 mg or placebo. Dexamethasone also was given on day 1 (10 mg given to the fosaprepitant group and 20 mg given to the placebo group). Aprepitant is known to increase plasma dexamethasone concentrations when used in combination with dexamethasone; therefore, to achieve comparable plasma levels of dexamethasone, the fosaprepitant group received a half dose of dexamethasone on days 1 and 2 only. On day 2, both groups received dexamethasone 4 mg and 8 mg, respectively. On day 3, both groups received dexamethasone 8 mg IV, administered in the morning.

• The study consisted of 340 participants.
• Participants' ages ranged from 25-86.
• The majority of patients were male (74%), and 26% were female.
• Diagnoses were respiratory (71%), genitourinary (10%), digestive (8%), head and neck (7%), and other (4%).
• In the standard (placebo) group, 64% of the participants did not consume alcohol whereas, in the fosaprepitant group, 50% had no alcohol intake.
   

This was a multisite study conducted at 68 institutions in Japan.

All patients were in active antitumor treatment.

This was a multicenter, placebo-controlled, double-blind, randomized, parallel study.

Patients kept self-assessment symptom diaries. Vomiting was defined as one episode of emesis or retching; nausea was assessed on most intense during a 24 hour-period of time.

• The percentage of patients who achieved a complete response (CR) in the overall phase (1-120 hours) was significantly higher in the fosaprepitant group than in the control group (64%, 95% confidence interval [CI] 16%-46%) versus 47% (95% CI, 10%-36%, p = 0.0015).
• CR rates in the acute and delayed phases were significantly higher in the fosaprepitant group than in the control group (acute phase: 94% versus 81%, P = 0.0006; delayed phase: 65% versus 49%, p  = 0.0025).
• Although the prevalence of a CR was decreased in the delayed phase, the difference between the two groups was higher in the delayed phase than in the acute phase (16% versus 13%).
• In patients who had received cisplatin and experienced vomiting, CR rates in the overall phase were higher in the fosaprepitant group than in the control group (60% versus 30.3%).
• Significant nausea in all phases and percentages of those with no rescue therapy in the overall phase did not differ significantly.

A single-dose administration of fosaprepitant (150 mg), used in combination with granisetron and dexamethasone, was found to be well-tolerated and effective in preventing CINV in patients receiving HEC, including high-dose cisplatin.

• A risk of bias exists because of the sample characteristics.
• Although the two groups had comparable numbers of individuals with a history of vomiting during pregnancy and previous treatment with cisplatin, the fosaprepitant group had slightly more individuals with a history of motion sickness, which is associated with higher susceptibility to nausea and vomiting. 
• The fosaprepitant group had slightly more individuals with alcohol use, which is associated with slightly less nausea.  
• Women are known to experience more acute nausea and vomiting than do men. In this study, 76% of the population was men.

The use of single-dose fosaprepitant (150 mg) in combination with granisetron and dexamethasone has shown effectiveness in preventing nausea and vomiting in patients receiving highly emetogenic antineoplastic therapies, such as cisplatin.

This article provided a review of the history of antiemetic development and use, a brief overview of relevant professional guidelines, and recent research on pharmacokinetics and outcomes with palonosetron. A meta-analysis on studies with two different doses of palonosetron was provided. No specific search strategy or research evaluation approach was reported.

• Palonosetron has a longer plasma half-life (approximately 40 hours) than other 5-HT₃ receptor antagonists (approximately 5–12 hours half-life).
• Palonosetron has a much higher bonding affinity for the 5-HT₃ receptor.
• Additional less clear differences are seen at the cellular level with palonosetron.
• Review of findings with palonosetron with multiday chemotherapy have shown complete response rates that are about twice that of historically reported prevention rates with other medications.
• Various research studies of palonosetron were reviewed. No firm conclusions were drawn regarding superiority of any particular regimen.

• Little research and description of rescue therapy and the most effective rescue approaches were provided.
• A lack of clarity exists in the border between acute and delayed CINV, particularly with multiday therapy.
• The most appropriate and effective dosage of palonosetron is controversial.
• Current guidelines related to CINV may need to be evaluated with the advent of new medications.

Pharmacokinetics and effects of palonosetron suggest it may have greater efficacy, particularly with delayed nausea and vomiting. This review points to a number of issues that should be considered in the design of future studies in this area.

The study goal was to assess the efficacy of pregabalin in the treatment of oxaliplatin-induced neurotoxicity.

Patients receiving oxaliplatin with grade 2 and 3 sensory neuropathy were treated with pregabalin up to a target dose of 150 mg orally three times a day. Neurologic symptoms were serially evaluated before treatment initiation with pregabalin and every two weeks thereafter, recording intensity and duration of the symptom. Interference with activities of daily living (ADLs) were evaluated. Patients started pregabalin at 50 mg three times per day. If tolerated, the dose was increased by 50 mg increments until symptoms improved to a max of 150 mg three times per day.

• The sample consisted of 23 patients (14 men, 9 women) with gastrointestinal cancer.
• Age range of the participants was 50–71 years.
• Patients had grade 2 or 3 oxaliplatin-induced sensory neuropathy based on National Cancer Institute common toxicity criteria.
• Patients were excluded if they had preexisting neuropathy from diabetes, alcoholism, CNS disease, or neurotoxic chemotherapy.

The study was conducted at an outpatient university setting in the United States.

The study had a prospective trial design.

National Cancer Institute common toxicity criteria

Five of the 23 participants were escalated to 150 mg of pregabalin with benefit and tolerance. Seven of the 23 escalated to 100 mg with benefit and tolerance. Four stopped due to no benefit, five could not be increased above 50 mg three times daily, two continued at this dose, and three stopped because of CNS side effects. Onset of benefit observed in 2–6 weeks. Three patients' neuropathy improved from grade 3 to grade 2, two patients improved from grade 3 to grade 1, and six patients improved from grade 2 to grade 1. No patients remained at grade 3 and five remained stable at grade 2. The five most common toxicities of pregabalin were dizziness, headache, somnolence, dry mouth, ataxia, and tremor.

Pregabalin at a dose of 100 mg–150 mg three times daily appears to decrease sensory neuropathy in some patients receiving oxaliplatin. Pregabalin was associated with side effects that limited the ability to tolerate the medication or dose escalation.

• The study had a small sample size (less than 30).
• The study also lacked a comparison or control group.
• The NCI toxicity criteria may not be valid to measure neuropathy.
• Results may be difficult to generalize to other groups of patients with cancer.

Pregabalin may be another alternative in treating chemotherapy-induced neuropathy for some patients. Findings suggest that pregabalin is not effective for everyone. In addition, the drug is expensive and is a controlled substance, which can limit the use. Pregabalin has side effects that need to be considered, including CNS side effects that required drug discontinuation. Patients receiving this agent need to be monitored appropriately for both effectiveness and potential side effects.