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.

• The author created an algorithm for the management of palmar-plantar erythrodysesthesia (PPE), which includes the following patient education prior to initiation of treatment with fluorouracil and capecitabine.
  • Skin care
    • Reduce friction and pressure, including kneeling for long periods of time; leaning on elbows; power walking, jogging, or regular walking for long periods of time; using hand tools; and gardening.
    • Wear sunscreen.
    • Avoid exposure to heat.
    • Use mild soap to bathe; pat (do not rub) skin to dry.
    • Keep shower and bath water lukewarm to cool; avoid hot tubs and long exposure to hot water.
    • Keep skin moist; gently apply moisturizing creams or topical emollients. Apply at night and wear loose-fitting cotton gloves.
    • Put hands and feet in cool water to relieve symptoms.
  • Clothes
    • Wear comfortable, loose-fitting clothes, shoes, and gloves.
    • Wear slippers when possible.
    • Avoid wearing rubber gloves (dishwashing gloves) because they retain heat.
  • Symptoms
    • Call when signs or symptoms first appear.
    • Do not wait and see whether symptoms worsen.
• The algorithm provided guidelines for dose reduction and dose interruption for treatment with fluorouracil and capecitabine.
• The author also recommended starting vitamin B6 (pyridoxine) at 50 mg TID.

Multiple interventions can be implemented to prevent or minimize PPE, including teaching patients to avoid friction and exposing their skin to heat.

A 45-minute music-assisted intervention with relaxation imagery sessions was provided twice a week by a trained therapist from the date of enrollment in the study to discharge.

• The sample consisted of 19 patients aged 5–65 years old.
• Sample criteria were bone marrow transplant recipients older than four years of age undergoing active treatment.

The study was conducted at a university bone marrow transplant center.

Patients were undergoing the active treatment phase of care.

The study had a case-controlled, nonrandomized convenience sample design.

Patient self-reported pre- and postintervention nausea and pain on a 0–10 scale. Time to engraftment also was measured.

Nausea, pain, and time to engraftment decreased from pre- to postintervention.

The intervention was implemented successfully with a very ill population (i.e., transplant environment).

• Subjects were not randomized; the study did not inventory personality and other factors that influence bone marrow transplant outcomes.
• The intervention was delayed until after transplantation.
• The frequency of the intervention was lower than planned because of staff perceptions that patients were too sick to participate.
• Time and attention control condition was not provided to the control subjects.

To examine the effect of a planned educational program on symptom control

Patients were randomly assigned to the education or waitlist control/usual care group. The educational intervention consisted of face-to-face educational sessions prior to each chemotherapy cycle provided to patients, caregivers, and family members. Symptom management education, support, and opportunity for discussion were provided.

• N = 140   
• MEAN AGE = 58.9 years
• MALES: 45%, FEMALES: 55%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: All had hematologic cancers and were beginning initial chemotherapy.
• OTHER KEY SAMPLE CHARACTERISTICS: Sixty-four percent were married, and 22% had no more than primary education.

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

PHASE OF CARE: Active antitumor treatment

Randomized, controlled trial

Not specified

The prevalence of chemotherapy-induced nausea and vomiting and difficulty sleeping were significantly lower after the intervention in the education group (p < 0.001), whereas the prevalence of these symptoms increased in the control group.

The findings suggest that an educational intervention can be beneficial in managing symptoms related to cancer treatment.

• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Method of randomization not described
• How symptom data were measured/obtained is unclear.

Patient education may be helpful in managing symptoms during cancer treatment. Education is necessary but may not be sufficient for symptom control.