To investigate the effects of modafinil on fatigue, depression, cognitive impairment, and health-related quality of life in patients with primary brain tumors

The intervention consisted of subjects receiving modafinil versus a placebo over six weeks. The week 1 dosage was 100 mg twice daily and the weeks 2–6 dosages were 200 mg twice daily. The cross-over occurred after the completion of week 6; thus, subjects who initially received the placebo followed the same dosing schedule over the next six weeks while those who had taken modafinil previously were given a placebo. Neuropsychological assessments and self-report measures were completed at baseline, six weeks, and 12 weeks.

• N = 37  
• AVERAGE AGE = 48.16 years (SD = 12.02 years)
• MALES: 37.8%, FEMALES: 62.8%
• KEY DISEASE CHARACTERISTICS: Gliomas and meningiomas with stable tumor status for six months
• OTHER KEY SAMPLE CHARACTERISTICS: Subjects had to score > 27 on the Checklist Individual Strength Test indicating the presence of fatigue. Exclusions include psychiatric disease or depressive disorders and medication interactions with modafinil.  

• SITE: Multi-site    
• SETTING TYPE: Outpatient    
• LOCATION: VU University Medical Center (Amsterdam), Academic Medical Center (Amsterdam), and Medical Center Haaglanden (Hague)

PHASE OF CARE: Multiple phases of care

Randomized, controlled, double-blinded clinical trial using a cross-over design. Measurements were performed at baseline, six weeks, and 12 weeks.

• Rey Auditory Verbal Learning Test (RAVLT)
• Memory Comparison Test
• Stroop Color and Word Test (Stroop)
• Letter Digit Substitution Test
• Concept Shifting Test (CST)
• Categorical Word Fluency Test
• Checklist Individual Strength (CIS)
• Center for Epidemiologic Studies Depression Scale (CES-D)
• Medical Outcomes Study Short-Form Health Survey (MOS SF-36)
• Medical Outcomes Study Subjective Cognitive Functioning Scale (MOS)

The CIS severity and reduced motivation scores for fatigue were lower after treatment with both modafinil (p = 0.01, p = 0.021) and placebo arms (p < 0.001, p = 0.027), but there was no difference in scores between trial arms. Significant improvements in working memory (p = 0.04, p = 0.043), information-processing (p = 0.036, p = 0.04), and attention (p = 0.015, p = 0.013) were found after treatment with modafinil and the placebo, respectively. There were no differences in scores between trial arms. Health-related quality of life measured by the physical component summary of the SF-36 was significantly improved for both modafinil (p = 0.001) and placebo arms (p = 0.008). There were no differences in depressive symptoms following modafinil or placebo.

The results indicate that there were no significant differences observed in fatigue, cognitive functioning, health-related quality of life, and mood between modafinil and a placebo. These findings may be related to the study design, duration of treatment, low study accrual, subject withdrawals, and lack of longitudinal follow-up.

• Small sample (< 100)
• Subject withdrawals ≥ 10%

Findings do not support the use of modafinil to improve fatigue, cognitive functioning, mood, and health-related quality of life in patients with brain tumors.

To determine factors that impact health-related quality of life (HRQOL) and mastery of caregivers of patients with high-grade glioma, and to investigate if a structured intervention consisting of psycho-education and cognitive behavioral therapy (CBT) leads to an improvement in the mental component of HRQOL and mastery of caregivers

Caregiver dyads randomly were assigned to the intervention group or care as usual group. The intervention group consisted of six one-hour sessions with a psychologist for CBT and psycho-education regarding disease-specific symptoms. Participants completed questionnaires concerning their perception of the patients' HRQOL, neurologic functioning, cognitive functioning, their own HRQOL perceptions, and feelings of caregiver mastery at baseline (prior to randomization) and every two months thereafter until eight months later, five times total.

• N = 56 caregiver dyads  
• MEAN AGE = 50 years
• MALES: Intervention group = 26%, control group = 48%; FEMALES: Intervention group = 74%, control group = 52%
• KEY DISEASE CHARACTERISTICS: High-grade glioma stage III/IV
• OTHER KEY SAMPLE CHARACTERISTICS: Participants were informal caregivers (defined as a spouse or significant other providing at least 21 hours of care per week); aged 18 years or older; 57% were receiving active treatment during the study 

• SITE: Multi-site    
• SETTING TYPE: Outpatient  
•  LOCATION: VU University Medical Center (Amsterdam)/Academic Medical Center (Amsterdam), and Medical Center Haaglanden (Netherlands)

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Palliative care

• Randomized, controlled trial

• MOS 36-item short form survey (SF-36)
• Caregiver mastery scale
• MOS Cognitive Functioning Scale
• Brain cancer module

Caregivers' HRQOL and caregiver mastery were associated with patient-related factors at baseline. A positive correlation was found between a positive mental functioning (MCS) of the patient and a positive MCS of the caregiver. Feelings of mastery in the intervention group increased over time, while feelings of mastery in the control group showed the opposite pattern. Those who received the intervention maintained a more stable level of mental functioning and showed modest improvement in feelings of mastery in comparison to the control group. Patients' HRQOL and neurologic functioning were found to be related to HRQOL and feelings of mastery of the informal caregiver at baseline. The intervention helped caregivers in maintaining a stable level of HRQOL and improved feelings of mastery over an eight-month period.

The findings from this RCT suggest that informal caregivers can benefit from a psychological CBT intervention because it is a helpful tool in maintaining a stable level of mental functioning and caregiver mastery.

• Small sample (less than 100)
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Findings not generalizable as a result of high attrition
• Intervention expensive, impractical, or training needs—significant time/burden for the caregiver (burdensome)
• Subject withdrawals 10% or greater
• Other limitations/explanation: Approximately 24% died prior to study conclusion

Future nursing practice should focus on offering supportive interventions to patients with high-grade glioma and their informal caregivers. Further research should continue to look at the effects of a psychological intervention on HRQOL and feelings of mastery of informal caregivers of the high-grade glioma patient population. Findings suggest that CBT interventions can be of benefit to caregivers.

Evaluate the efficacy of venlaxafine and clonidine for hot flashes in patients with breast cancer

Patients were randomly assigned to receive 75 mg venlafaxine,  0.1 mg clonidine, or placebo daily.  Subjects were stratified by age, duration of hot flashes, concurrent endocrine therapy, and previous chemotherapy.   Patients were treated for 12 weeks.  Hot flash scores at week 12 were compared among the three groups.

N  80 AGE   Median = 49, range 28-71

MALES (%)          FEMALES (%)100%

KEY DISEASE CHARACTERISTICS 31% had age related symptoms, and 99% were post menopausal after breast cancer treatment.  52% received endocrine treatment
 

SITE  Multi-site  SETTING TYPE  Outpatient  LOCATION Netherlands

PHASE OF CARE Late effects and survivorship

 Double blind placebo controlled RCT

• Daily diary of frequency and severity of hot flashes - mild, moderate, severe categorization and calculation of daily hot flash scores
• Groningen Sleep Quality Index
• Hospital Anxiety and Depression Score
• Sexual Activity Questionnaire
   

Hot flash scores were lower in the clonidine group than the placebo group at week 12 ( p = .03), and lower in the venlaxafine group than placebo, though not statistically significant ( p = .07).  Over the 12-week period, reduction in the venlaxafine group was 41% ( P<.001), 26% in the clonidine group ( p=.045), and 29% in the placebo group (p<.001).  Those on venlaxafine tended to have some loss of appetite ( p = .003) as well as symptoms of nausea.  Sleep and sexual function were not different between the two treatment groups.  At week 12, anxiety and depression scores were higher in the venlafaxine than the clonidine group. (p = .03).  Significantly lower hot flash scores began in the venlafaxine group compared to placebo in weeks 1-4 (p =.01), and in the clonidine group, lower scores began compared to placebo in weeks 5-8 ( p = .04)

Both venlafaxine and clonidine were slightly more effective than placebo in reducing hot flash symptoms in this group of patients. However, over the 12 weeks, all study groups showed significant reduction in symptoms.

• Questionable protocol fidelity
• Other limitations/*explanation  Authors state that the final sample was underpowered.  It is noted that not all patients were compliant with the medications, but is not clearly stated how compliant they were or were not.  No information is given regarding any missing diary data, and reliability of diary and self-report of severity of hot flashes is not clear.  Follow up period was relatively short, so longer term efficacy is not clear.

Findings suggest that venlafaxine and clonidine may be of benefit in reducing hot flash symptoms in women with breast cancer. However, further research is needed for support, because placebo group also showed reduction in hot flashes. Some patients did have side effects from these medications; patients should be monitored for nausea, changes in appetite, anxiety, and depression if these medications are used.

To evaluate the effectiveness and safety of aprepitant related to the incidence and severity of chemotherapy-induced nausea and vomiting (CINV) when added to a standard antiemetic regimen for highly or moderately emetogenic chemotherapy in pediatric patients

Both male and female patients received a standard antiemetic regimen of ondansetron 0.45 mg/kg and dexamethasone 7 mg/². In addition, they also received oral (solution or capsule) aprepitant with weight-based dosing based on the facility’s dosing table. Issues related to quality of life, such as severity of nausea, frequency of vomiting, appetite, and effect on activities of daily living (ADLs) were assessed using a survey. Since there are few studies using aprepitant in young patients weighing < 40 kg, the safety and tolerability of aprepitant in this population was the focus of this study.

• N = 11 patients (20 encounters)  
• MEAN AGE = 9.55 (4.85) years (range = 12 months–17 years)
• MALES: Not identified, FEMALES: Not identified
• KEY DISEASE CHARACTERISTICS: Confirmed malignancy
• OTHER KEY SAMPLE CHARACTERISTICS: Patients received a cycle of highly or moderately emetogenic chemotherapy.

• SITE: Single-site  
• SETTING TYPE: Not specified  
• LOCATION: Not indicated

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Pediatrics 

Prospective, observational study

A patient survey was created by the investigators using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) grading system v4.0 and a 4-point Likert scale. It was completed at baseline, every day in which chemotherapy was administered, and for five days after the completion of chemotherapy. The survey evaluated the occurrence and severity of nausea, vomiting, appetite, and affect on ADLs during the phases of acute (0–24 hours), delayed (1–5 days), and overall phase (acute and delayed) after chemotherapy. The survey was administered by a study investigator or sent home with the patient’s caregiver. Complete response (CR) was defined as no nausea, vomiting, or no use of rescue drugs during the acute phase.

A total of 7 out of 16 (38.9%) CRs were achieved. No vomiting was reported in the overall (acute and delayed) phase in 16 out of 18 encounters (88.9%). In 5 out of 17 encounters (29.4%), no nausea was experienced in the overall phase. There was no interference in ADLs in 47.1% and no interference with appetite in 10 out of 18 (55.6%) patients. Rescue medications were not required in the acute phase for 7 out of 11 patients. There were no directly attributable adverse effects related to the systemic absorption of aprepitant, and it was found to be well-tolerated in this pediatric study population.

Oral aprepitant administration was found to be safe in patients as young as 12 months in moderate and highly emetogenic chemotherapy. During the study period, complete responses (no nausea, vomiting, or use of rescue drugs) were experienced in 33.3% of patients.

• Small sample (< 30)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment) 
• Risk of bias (sample characteristics)
• Selective outcomes reporting
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Findings not generalizable
• Other limitations/explanation: The range of ages from 12 months to 17 years in a small sample makes it difficult to come to valid conclusions about the results. No tool was used to measure the safety of aprepitant in this population.

In the study population, weight-based dosing of oral aprepitant was well-tolerated and did not cause any systemic adverse reactions.

To examine fatigue levels in patients supported by a mistletoe preparation compared to patients who did not receive mistletoe

Data were extracted from the medical records of patients from the time of diagnosis or surgery (visit 1), during postoperative chemotherapy or chemoradiotherapy (visit 2), and at the end of postoperative therapy (visit 3). Patient complains related to fatigue and symptoms of inflammation were noted by the physician via interview. The results of patients allocated to mistletoe therapy were compared to those of the control patients. Mistletoe was provided as an injectable extract preparation that was given subcutaneously at a total average dose of 16–20 mg per week.

• N = 324  
• AGE = Not provided
• MALES: Not provided, FEMALES: Not provided
• KEY DISEASE CHARACTERISTICS: All patients had colorectal cancer and were receiving 5-fluorouracil-based chemotherapy.

• SITE: Multi-site    
• SETTING TYPE: Not specified    
• LOCATION: Germany

• PHASE OF CARE: Active antitumor treatment

Retrospective, observational cohort study

Specific measurements were not described. Signs of inflammation and cancer-related fatigue were apparently coded by physicians as “yes” or “no” to indicate the presence of clinical signs.

There was a significantly increased odds ratio of suffering with fatigue among patients in the control group at visits 2 and 3 (p < 0.001). However, by visit 2, 85% of those in the mistletoe group had dropped out, and by visit 3, only 16 patients remained in the mistletoe group. The results regarding inflammation were not described.

This report provides insufficient evidence regarding the effects of mistletoe therapy on cancer-related fatigue.

• Small sample (< 30)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Subject withdrawals ≥ 10%  
• Other limitations/explanation: The study design, lack of clear objective methods to measure outcomes, and extremely high drop-out rate limit the usefulness of the findings reported. The actual dosages, timing, and duration of mistletoe therapy were not described.

This study does not provide any strong evidence regarding the efficacy of mistletoe extract for the management of cancer-related fatigue, and it does not provide evidence regarding the impact of this therapy on inflammatory markers. Inflammation is a suggested mechanism that may influence fatigue in patients with cancer, and mistletoe extract has been proposed as an intervention to reduce inflammation. Well-designed studies examining the potential effects of mistletoe extract in these areas are needed.

To evaluate the safety and efficacy of micafungin for antifungal prophylaxis in pediatric patients at high risk for fungal infection

Children who were intolerant to polyenes and axoles or in whom theses were otherwise contraindicated were given 3–4 mg/kg micafungin twice weekly. Micafungin was begun when the patient could not take other antifungals and was continued until hematopoetic recovery after chemotherapy or until 100 days after HCT. Trough concentrations were determined from blood drawn prior to micafungin infusion, and peak levels were obtained 30 minutes after the end of the infusion.

• N = 21
• MEDIAN AGE = 9 years
• AGE RANGE = 0.2–16 years
• MALES: 66.6%, FEMALES: 33.4%
• KEY DISEASE CHARACTERISTICS: All relapse, Non-Hodgkin lymphoma, AML, or undergoing allogeneic HCT

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

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Pediatrics

• Observational retrospective

• IFD defined according to European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG)
• Peak and trough micafungin concentrations

There was no premature discontinuation of micafungin due to related adverse events. Proven or probably invasive fungal infection did not occur in any patients.

Findings suggest that intermittent micafungin for antifungal prophylaxis can be safe and effective in high-risk pediatric patients. Additonal larger studies are needed to confirm these results.

• Small sample (less than 30)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment) 

There are a number of limitations to the use of oral triazoles for routine antifungal prophylaxis, and micfungin has been used for prevention and treatment of candida infections in children. This study showed that a larger dose, delivered intermittently, may be a safe and effective alternative for antifungal prophylaxis in high-risk children with cancer. The ability to not have to provide infusions daily can be an attractive and convenient alternative to daily treatment. This study has several important limitations, so additional well-designed research to confirm these findings in larger samples is needed.

To compare the efficacy and tolerability of the granisetron transdermal delivery system (GTDS) to daily oral granisetron for the control of chemotherapy-induced nausea and vomiting (CINV)

Patients were randomized to oral (2 mg per day for 3–5 days) or transdermal (one GTDS patch over 7 days) granisetron before receiving multiday chemotherapy. Patients received placebo capsules or capsules according to group assignment. Corticosteroids and rescue medications were given at the discretion of the investigator. Patients were followed for 14 days after chemotherapy.

• The study consisted of 582 participants.
• The mean age of participants in the GTDS group was 54 years (SD = 13 years). The mean age of participants in the oral granisetron group was 55 years (SD = 14 years).
• In the GTDS group, 52% of patients were female and 48% were male. In the oral granisetron group, 51% were female and 49% were male.
• Diagnoses were not provided.
• Patients were receiving the first cycle of a new multiday moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC) regimen.

The study was conducted at multiple sites in Europe, the United States, Mexico, and India.

This was a randomized, double-blind, controlled trial.

Patients recorded the following in diaries daily.

• Vomiting, presence and severity, on a five-point scale ranging from 1 = none and 5 = very severe.
• Nausea, presence and severity, on a four-point scale ranging from 1 = none and 4 = severe.

Complete control (CC) was defined as no vomiting or retching, no more than mild nausea, and no use of rescue medication from the first administration until 24 hours after the last administration of chemotherapy.

• GTDS was not inferior to oral granisetron in CC.
• The percentage of patients achieving complete response (CR) or total control (TC) was not significantly different.
• Time to failure and time to treatment CC failure were similar.
• In patients receiving three- and five-day chemotherapy regimens, CC and CR were similar between the GTDS and oral granisetron groups.
• The GTDS group reported more constipation, and the oral granisetron group reported more headaches.
• In the experimental group, 65% of patients achieved CR with oral graniestron, and, in the control group, 60% of patients achieved CR with oral granisetron.

The GTDS provided effective, well-tolerated control of CINV associated with moderately or highly emetogenic, multiday chemotherapy.

• Diagnoses were not reported.
• No information was provided or subgroup analysis done on the use of dexamethasone or rescue medications.
• No differentiation or analysis was provided regarding acute versus delayed nausea or between those receiving MEC or HEC.
• No neurokinin 1 (NK1) receptor antagonists were used.

GTDS could be an option for CINV from multiday chemotherapy regimens. Further research to determine the role of this approach within an overall antiemetic regimen is warranted.

To establish the noninferiority of sustained-release granisetron (APF530) for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) compared with palonosetron following highly emetogenic chemotherapy (HEC) and/or MEC chemotherapy in a subpopulation of patients with breast cancer, and to show the superiority of APF530 for the prevention of delayed CINV following HEC with cycle 1 of chemotherapy.

Patients were stratified based on either moderate or high emetogenicity of the chemotherapy. Patients received both IV and subcutaneous injections. Group 1 received 250 mg of APF530 subcutaneously and placebo IV, group 2 received 500 mg of APF530 subcutaneously and placebo IV, and group 3 received placebo subcutaneously and IV palonosetron 0.25 mg. APF530 was given 30 minutes prior to chemotherapy. At the completion of cycle 1, patients who received palonosetron were offered the option to remain in the study. These patients were then rerandomized 1 to 1 to receive doses of 250 versus 500 mg of APF530 subcutaneously during cycles 2–4. Treatment cycles ranged from 7 days–28 days. Rescue medications were permitted with the exception of granisetron, palonosetron, and aprepitant.

• N = 618   
• MEAN AGE = Moderately emetogenic group (53.3 years in APF 250 mg, 54.3 years in APF 500 mg, 55 years in palonestron only); highly emetogenic group (50.3 years in APF 250 mg, 49.8 years in APF 500 mg, 52.6 years in palonosetron only)
• MALES: Less than 2% (n = 5), FEMALES: 98–100% (n = 603)
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Breast cancer, does not report staging
• OTHER KEY SAMPLE CHARACTERISTICS: Multiple chemotherapy regimens with less than 70% receiving AC; mostly Caucasian and Asian

• SITE: Multi-site   
• SETTING TYPE: Not specified    
• LOCATION: Multiple cancer centers across the United States, India, and Poland

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

Prospective, multicenter, randomized, double-blind and double-dummy, parallel-group, phase-III noninferiority trial. Groups were broken into highly emetic and moderately emetic based on Hesketh scores.

• Instruments used to measure CINV are not articulated in this paper.  
• Complete response defined as no emesis and no use of rescue medication.

CR rates with the experimental drug at 250 and 500 mg were not significantly different from those with palonosetron for both HEC and MEC regimens. The effectiveness of APF530 improved in later cycles, although at that point, those patients were no longer receiving palonosetron. No significant differences existed between groups in the samples. No noticeable differences existed between the breast cancer group and the overall population of the study.

Safety: Patients receiving APF530 had more complaints of injection site pain compared to palonosetron. No difference in adverse events existed between the breast cancer group and the overall population of the study.

APF530 is effective in acute and delayed CINV in patients with breast cancer. The side effect profile was similar in all arms of the study and included fatigue, constipation, and headache. The trend to better response is not a reflection of palonosetron, as this agent was not used after cycle 1.

• Measurement/methods not well described
• Unknown instruments to measure CINV
• This is a secondary analysis of a previously published paper from 2014.

Sustained-release granisetron can provide another alternative intervention for CINV prophylaxis; however, it does require subcutaneous injection. Further research is needed to establish the comparative effectiveness of this medication within overall CINV antiemetic regimens.

To determine if a response to antiemetic APF530 is sustained over multiple cycles of chemotherapy

This study consisted of three treatment arms. During cycle 1, group 1 received 250 mg of subcutaneous APF530, group 2 received 500 mg of subcutaneous APF530, and group 3 received palonosetron at 0.25 mg IV in addition to an subcutaneous placebo before moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC). Patients receiving MEC also received dexamethasone at 8 mg IV 30–90 minutes before chemotherapy. Patients receiving HEC were given 20 mg of IV dexamethasone followed by 8 mg orally twice per day on days 2–4. In cycles 2–4, palonosetron was discontinued, and all patients in the palonosetron group were randomized to receive either 250 mg or 500 mg of APF530 with dexamethasone (dosing as previously stated). Cycles were separated by a range of 3–28 days. Rescue antiemetics were allowed as needed. Local anesthetic was administered to the injection site before the study drugs were administered. Study subjects kept diaries of emetic episodes, the use of rescue medications, and the severity of nausea for each 24-hour period after receiving chemotherapy. Adverse events were documented according to standard toxicity criteria. Complete response (CR) was defined as no rescue medications and no emetic episodes. Complete control (CC) was defined as no more than mild nausea and no rescue medications. Total response was defined as no nausea and no rescue medications.

• N = 580 (four cycles) 
• MEAN AGE = 57 years
• MALES: 25%, FEMALES: 75%
• KEY DISEASE CHARACTERISTICS: Primarily breast, lung, and ovarian cancer; mean time since diagnosis was 0.7 years; scheduled to receive single-day MEC (Hesketh score 3 or 4) or single-day HEC (Hesketh score 5) as defined at the time of study
• OTHER KEY SAMPLE CHARACTERISTICS: The sample size in cycle 1 of the study was 1,389 patients. However, the sample size for subsequent cycles was the number of patients who remained in the study using a modified intent-to-treat population of patients who received the drug and had efficacy data. 

• SITE: Multi-site    
• SETTING TYPE: Not specified    
• LOCATION: United States, India, and Poland

• PHASE OF CARE: Active antitumor treatment

Prospective, multicenter, randomized, double-blinded, placebo-controlled, parallel-group, phase 3 trial with stratification according to the emetogenicity of regimens

• Efficacy measures were assessed from patient diaries which recorded emetic episodes, the use of rescue medication, and the severity of nausea for each 24-hour period after chemotherapy (the specific tool to measure the severity of nausea was not described).
• Adverse events were assessed using standard toxicity criteria.
• Efficacy was measured as the percentage of patients who achieved CR (no emetic episodes and no rescue medication) during the acute and delayed phases of chemotherapy.
• Sustainability over cycles was measured as the proportion of patients with CR during the acute and delayed phases, the time to first emetic episode, the time till the first rescue medication, and the time till the first treatment failure in cycles 2–4.
• Treatment comparisons were based on the Fisher exact test.

In cycle 1, ≥ 75% of both doses of APF530 had acute-phase CR, and ≥ 50% had delayed-phase CR. There was a similar response rate for cycles 2–4 with the HEC group having a slightly better response than the MEC group. Acute phase CR increased over the four cycles of HEC (81%–88%) for APF530 500 mg dose and CR increased from 67% to 83% in the delayed phase for this group. In patients who received palonosetron in cycle 1, ≥ 90% of those who had CR maintained CR in subsequent cycles (with APF530). Half of the of MEC and palonosetron group that did not achieve CR in cycle 1 achieved CR in next cycle (with APF530). No treatment-related serious adverse events were seen. Common adverse events across all cycles included constipation, headache, fatigue, and diarrhea for patients who received APF530. APF530 at 250 or 500 mg caused injection site reactions. Most were mild, and greater than than 3% were moderate.

This study demonstrated sustained responses in the acute and delayed phases of chemotherapy over four cycles in both 250 mg adnd 500 mg oses of APF530. Patients who responded to APF530 in cycle 1 also responded in cycles 2–4. Patients receiving palonosetron for chemotherapy-induced nausea and vomiting had a similar response to APF530 in subsequent cycles. Patients receiving APF530 had mild adverse effects primarily related to injection site reactions.

• Measurement/methods not well described
• Subject withdrawals ≥ 10%  
• Other limitations/explanation: The Hesketh scoring system has changed since the study was conducted. Some regimens considered MEC at the time of the study are now considered HEC, changing the efficacy of MEC versus HEC regimens in the current system. The treatment group size and characteristics varied from cycle to cycle. Patients who no longer received the study drug or who had no data were removed, resulting in a greater than 42% drop in the number of subjects for the final cycle of chemotherapy. It was difficult to read the results of the data in bar graph format. 

APF530 was an effective 5HT3 blocker for the prevention of chemotherapy-induced nausea and vomiting in HEC and MEC regimens, and its efficacy was sustained over multiple cycles. There was no significant benefit in using higher doses over the 250 mg dose. There was a potential for injection site reactions caused by the subcutaneous route of APF530, which may affect patients' quality of life.

To examine the efficacy of three different doses of oral palonosetron compared to IV palonosetron for chemotherapy-induced nausea and vomiting (CINV) management and to explore the contribution of dexamethasone to these regimens

Patients were randomized to one of four different groups: oral palonosetron at 0.25, 0.5, and 0.75 mg or IV palonosetron at 0.25mg. Within each of these groups, patients were randomized to receive a single 8 mg IV dose of dexamethasone or placebo. Patients were stratified by age and by whether they had received previous chemotherapy. All patients were receiving single day chemotherapy. The noninferiority margin for analysis was set at a maximum difference in complete response rate at 24 hour of 15%.

• The study looked at 635 patients with a mean age of 56.7 years.
• The sample was 47% male and 53% female.
• Diagnoses were breast, colon, and lung.  All patients were receiving single-day, moderately emetogenic chemotherapy (MEC).
• Most patients were Caucasian or Hispanic.  Slightly more than half were chemotherapy naïve.

This was a multisite study conducted in outpatient settings in multiple countries.

All patients were in active antitumor treatment.

This was a randomized, double-blind, double-dummy trial.

• Complete response (CR) in the acute, delayed and overall phases was defined as no emesis and no rescue antiemetics.
• Nausea severity was rated on 4-point, Likert-type scale.

• In the acute phase, all of the oral doses were shown to not be inferior to IV palonosetron. In the delayed phase, none of the oral doses reached noninferiority to the IV dose.  In the overall phase, (0-120 hours postchemotherapy), only the 0.5 mg oral dose was found to be noninferior.
• CR was 77%–83% in the acute phase, 68%–75% in the delayed phase, and 61%–70% in the overall phase. 
• No differences were found across palonosetron groups in nausea.
• In general, in both the acute and delayed phases, subgroups that also received dexamethasone showed higher CR rates. 
• Use of rescue antiemetics was similar across study groups.  
• Adverse events were comparable across groups, with no apparent dose-response relationship.

Both oral and IV palonosetron formulations were shown to be effective in CINV prevention, and similar effects were seen at all three oral doses studied.  IV palonosetron may be more effective for reduction in CINV during the delayed phase. The addition of dexamethasone was associated with improved CR rates for both acute and delayed CINV.

• The measurements and methods were not well described.
• The findings are not generalizable.
• Other limitations include that the timing and method of nausea measurement were not well described and the findings are applicable to single-day MEC only.

Findings show that effectiveness of oral and IV palonosetron is similar, though the IV formulation may be slightly more effective for prevention of CINV during the delayed phase.   Findings also show that dexamethasone improves CINV control. Further research with multiday chemotherapy regimens and other emetogenic chemotherapy levels is warranted.  Findings continue to show that nausea is not as well controlled as emesis. High quality assessment of CINV in both acute and delayed phases is essential to ongoing planning for the most effective antiemetic approach for individual patients. A continued need exists to find effective interventions to reduce nausea as well as emesis.