To confirm the differential time course of action noted with a neurokinin 1 (NK1) receptor antagonist (RA) compared to a 5-HT₃ RA in the setting of cisplatin-based chemotherapy using the database from three large, phase III trials

Multivariate logistic regression models were used to assess the impact of the first emesis at different time intervals of aprepitant regimens compared to control regimens using a modified intent-to-treat approach. The endpoint was the frequency of first emesis during distinct time intervals from administration of chemotherapy through 120 hours postadministration.

The trials reported on a total of 2,383 patients.

The mean age range of patients was 52–59 years.

• In the Aprepitant group, the mean age of patients in study 1 was 56 years, the mean age of patients in study 2 was 59 years, and the mean age of patients in study 3 was 53 years.
• In the Control group, the mean age of patients in study 1 was 56 years, the mean age of patients in study 2 was 59 years, and the mean age of patients in study 3 was 52 years.

The percentage of the sample that was male was not reported but assumed to range from 0%–65%. The percentage of females ranged from 35%–100%.

• In the Aprepitant group, study 1 was 42% female, study 2 was 39% female, and study 3 was 99.5% female.
• In the Control group, study 1 was 43% female, study 2 was 35% female, and study 3 was 100% female.

In study 1 and study 2, primary cancer diagnoses were respiratory, urogenital, digestive, and other. In study 3, primary diagnosis was breast cancer.

The majority (59%–80%) were Caucasian.

A total of 1,527 patients were receiving cisplatin-based HEC and 856 were receiving anthracycline plus cyclophosphamide-based moderately emetogenic chemotherapy (MEC).

All patients were in active treatment.

This was a post-hoc analysis.

Measurement instruments and methods were not specified in this article.

With cisplatin-based, highly emetogenic chemotherapy (HEC), the aprepitant regimen was associated with a lower incidence of first vomiting compared to the standard regimen beginning at the 15–18 hour interval and beyond. This lowered incidence was maintained until the 48–60 hour interval, with the first vomiting incidence reduced by 38%–77%.

With anthracycline-cyclophosphamide-based MEC, the first vomiting incidence was markedly lower, as early as the 3–6 hour interval. This effect was maintained up to the 9–12 hour interval, with the first vomiting incidence reduced by 38%–61%.

Emesis induced by cisplatin is biphasic with the initial peak within 2 hours of cisplatin and the second peak starting 16–18 hours and lasting 48 hours after cisplatin. 5-HT₃ medications appear to be most effective in the first 12 hours after cisplatin while NK1-sensitive mechanisms appear to be more effective up to 60 hours after cisplatin.

Anthracycline and cyclophosphamide agents display a monophasic emesis pattern; therefore, better emetic control is noted with NK1-dependent medications much earlier in the treatment cycle.

No discussion was included on how data was collected within each study.

Cisplatin-based regimens require 5-HT₃-dependent medications within the first 12 hours and NK1-dependent medications thereafter.  Anthracycline- and cyclophosphamide-based regimens appear to be sensitive to both 5-HT₃- and NK1-dependent medications.

To prospectively determine the frequency of delayed nausea and vomiting with irinotecan-based chemotherapy following day 1 prophylaxis with a 5-HT₃ receptor antagonist and dexamethasone

All patients received irinotecan-based chemotherapy. All patients received a standard antiemetic regimen prior to chemotherapy consisting of dexamethasone (8 mg oral or IV) and a 5-HT₃ receptor antagonist (8 mg IV or 24 mg oral ondansetron, 100 mg IV or oral dolasetron, and 1 mg IV or 2 mg oral granisetron) given immediately prior to the start of chemotherapy only. No routine antiemetics were prescribed after day one for prophylaxis or delayed emesis. Palonosetron was not permitted in this study. All patients received a prescription for rescue therapy, only to be used during the first 120 hours. Patients were monitored for 120 hours after the initiation of irinotecan by the study coordinator who called at timed intervals to assist patients in completing diaries. During this study, patients only were observed on their first cycle of the irinotecan-based chemotherapy.

• This study consisted of 44 patients.
• The median age was 61 years with a range of 39-79 years.
• The sample was 84% male and 16% female.
• Patients had been diagnosed with colorectal cancer.
• All patients were receiving irinotecan-based chemotherapy (38 patients received a FOLFIRI regimen, five patients, received irinotecan in combination with cetuximab, and only one patient received irinotecan alone).
• One patient had a history of motion sickness, and three of the seven female patients (43%) had a history of morning sickness.
• To be included in the study, patients had to be older than 18 years of age and have European Cooperative Oncology Group Performance Status of 0–2.
• Patients with history of moderate to severe nausea or any vomiting with prior chemotherapy were not eligible.

The study was conducted at multiple outpatient settings through the St. Elizabeth’s Medical Center in Boston, MA; Holy Family Hospital in Methuen, MA; and the Institute for Radiology and Oncology of Serbia.

• All patients were in active treatment.
• This study has application to late effects and survivorship.

This was a prospective, observational study.

• Patient diaries were used to record the frequency and timing of vomiting or retching episodes and the use of rescue meds (1–5 retches over 5 minutes was counted as a single emetic episode).
• A four-point categorical scale was used to assess the extent of nausea experienced in the preceding 24-hour period (0 = none, 1 = mild [did not interfere with normal daily life], and 3 = severe [patients bedridden because of nausea]). 
• Complete control was defined as no emesis, no nausea, and no use of rescue antiemetics.
• Complete response was defined as no emesis and no use of rescue antiemetics.

• The majority (89%) of the 44 patients enrolled in the study had no emesis during the overall period, 9% experienced vomiting or retching during the delayed period, and 7% vomited during the first 24 hours after irinotecan administration.
• Fifteen patients (34%) experienced delayed nausea (mild in 11 patients, moderate in 4 patients). Six patients (14%) took rescue antiemetics during the delayed period.
• Delayed and overall complete response rates were 86% (acute), 82% (delayed), and 77% (overall).
• Complete control was 86% (acute), 64%(acute), and 59%(delayed).
• Achieving a complete response during the acute period predicted for a high likelihood of attaining a complete response during the delayed period (95%).

The results of the study showed efficacy in reducing or controlling delayed nausea and vomiting during the 24-hour period following administration of a camptothecin analogue, a moderately ematogenic  antineoplastic agent, when dexamethasone and a 5-HT₃ receptor antagonist was used as prophylaxis for acute chemotherapy-induced nausea and vomiting (CINV).

• The sample size was small.
• The sample was primarily male. No comparative control group and the male-to-female ratio may have affected results because of gender imbalance with a larger male population.

The use of dexamethasone and a 5-HT₃ receptor antagonist prior to administration of a camptothecin analogue is recommended in the literature and has been shown to be beneficial in controlling acute CINV, which contributes in reducing delayed nausea and vomiting.

To evaluate the efficacy and safety of IV palonosetron in preventing chemotherapy-induced nausea and vomiting (CINV) in patients with cancer who had incomplete control of CINV during their previous cycle of low-emetogenic chemotherapy (LEC)

A baseline clinical assessment was performed including demographics, history, physical exam, labs, and urinalysis, within 14 days of treatment. On day 1, eligible patients received an IV bolus injection of 0.25 mg palonosetron 30 minutes before their scheduled LEC regimen. Patients were then monitored 30 minutes after administration of LEC for any adverse reactions. Outcomes were recorded in patient diaries over a 120-hour period at the end of study visits on days 6, 7, or 8 after LEC administration. Investigators assessed presence of nausea and its severity and intensity, the number of emetic episodes, complete control rate, and the complete response rate for the acute phase (0–24 hours), delayed phase (24–120 hours), and overall response (0–120 hours). 

• The study reported on 34 participants.
• The mean age of the participants was 64.7 years (SD = 13.77 years).
• The sample was 31% male and 69% female.
• Patients had histologically or cytologically confirmed cancer
• The sample was 83% Caucasian, and the mean Karnofsky Performance Status score was 82.8. 
• All patients had received prior LEC that had induced vomiting or at least moderate nausea.
• Most patients (77.8%) consumed no alcohol.

This was a mutlisite study conducted in clinical settings at 10 centers in the United States.

• Patients were in active Treatment.
• This study has application to late effects and survivorship.

This was a prospective, single-arm, descriptive study.

• Patient diaries were used to record of the number of emetic events, use of rescue antiemetics, and measure of nausea on a 4-point Likert-type scale with 0 = no nausea to 3 = severe nausea.
• Complete response was defined as no nausea, vomiting, or need for rescue antiemetics.
• An end-of-study visit was conducted on day 6, 7, or 8.

The majority of patients (94.1%) required no rescues antiemetics in the postchemotherapy phase. In the acute postchemotherapy phase, 88.2% of patients experienced complete response. In the delayed phase, 67% experienced complete response. On two treatment-emergent adverse events occurred. Complete control rate was also noted in the acute and delayed phases. Overall, 73.5% of patients did not require rescue medications.

Palonosetron was effective in preventing CINV in both the acute and delayed postchemotherapy phases and was well tolerated in this group of patients who had a history of CINV with LEC. Unfortunately, type of cancer was not reported.

• The sample was small with fewer than 100 patients.
• No control group was included.
• Patients were receiving various chemotherapy regimens.

In patients with a history of CINV while receiving LEC, palonosetron can be considered a useful antiemetic option for acute and delayed post chemotherapy phases. A randomized study should be considered with a focus on specific LEC regimens. Nurses should note that 73% of patients did not require rescue antiemetics; however, 27% patients did need them.

To evaluate the efficacy of the addition of rolapitant to prevent chemotherapy-induced nausea and vomiting (CINV) in patients receiving carboplatin

Patients were randomly assigned to receive a single oral dose of 180 mg rolapitant or a matching placebo 1–2 hours before chemotherapy administration on day 1. All patients received granisetron on days 2 and 3. Patients receiving taxanes also were given dexamethasone. For five days, patients recorded vomiting, use of rescue medication, and nausea daily in a diary. Additional study assessment was obtained on day 6 of cycle 1 of chemotherapy. This report is a subset of a larger phase-III trial focusing on individuals receiving the first course of chemotherapy with a carboplatin-based regimen.

• N = 401   
• MEDIAN AGE = 63 years
• AGE RANGE = 23–88 years
• MALES: 54.9%, FEMALES: 45.1%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Multiple tumor types—lung was most prevalent
• OTHER KEY SAMPLE CHARACTERISTICS: All were receiving a moderately emetogenic chemotherapy (MEC) regimen.

• SITE: Multi-site   
• SETTING TYPE: Not specified    
• LOCATION: Multiple countries

• PHASE OF CARE: Active antitumor treatment

• Double-blind, randomized, placebo-controlled trial

• Visual analog scale (VAS) for nausea
• Functional Living Index-Emesis (FLIE)

Those receiving rolapitant had a higher prevalence of complete response (CR) for antiemetics in the overall phase (p < 0.001) and delayed phase (p < 0.001). No differences existed between groups for the response in the acute phase; 88%–91% across study groups had CR in the acute phase. No difference existed between groups in FLIE results. Nausea was also better controlled in the rolapitant group in the overall (p = 0.023) and delayed phases (p = 0.034) (patients reporting no nausea). No differences existed between groups in adverse events, and no serious adverse events occurred.

Rolapitant was shown to be effective for the prevention of emesis in patients receiving MEC. The proportion of patients reporting no nausea was also higher with rolapitant; however, only 62.5% had no nausea in the overall phase.

The findings support the use of rolapitant as part of a triple-drug regimen with a 5-HT₃ and dexamethasone for patients receiving carboplatin. NK1s are not routinely recommended for patients receiving MEC; however, this study showed significantly better control with the addition of an NK₁. A substantial proportion of patients continued to experience nausea, though this was also improved with use of rolapitant.

PHASE OF CARE: Active antitumor treatment

Three studies were included in the review.

The oral combination of NEPA and dexamethasone is an option for patients receiving highly emetogenic chemotherapy (including anthracycline and cyclophosphamide) to meet recommendations for triple-drug therapy.

• Focused guideline update only to include NEPA
• Studies reviewed did not specifically show that pediatric patients were included.

NEPA is a new drug that can be combined with NK1 and 5HT3 drugs. This drug provides both recommended agents in a single, oral medication. Patients who take NEPA rather than a typical regimen will not need IV administration, which can result in increased cost to the patient depending on individual insurance coverage.

To determine the best dose of netupitant (NEPA) used in combination with palonosteron for chemotherapy-induced nausea and vomiting (CINV) by evaluating the efficacy and safety of three different doses of netupitant (100 mg, 200 mg, and 300 mg)

• Day 1: Oral PALO 0.50 mg + Oral DEX 20 mg + placebo; Days 2–4: Oral DEX 8 mg bid
• Day 1: Oral NEPA 100 mg + Oral PALO 0.50 mg + Oral DEX 12 mg; Days 2–4: Oral DEX 4 mg bid
• Day 1: Oral NEPA 200 mg + Oral PALO 0.50 mg + Oral DEX 12 mg; days 2–4: Oral DEX 4 mg bid
• Day 1: Oral NEPA 300 mg + Oral PALO 0.50 mg + Oral DEX 12 mg; days 2–4: Oral DEX 4 mg bid
• Day 1: Oral PR 125 mg + IV OND 32 mg + Oral DEX 12 mg; Days 2–3: Oral APR 80 mg in morning + oral DEX 4 mg bid; Day 4: oral DEX 4 mg bid (exploratory arm)

• N = 677  
• MEDIAN AGE (of all groups) = 53–55 years
• MALES: 57%, FEMALES: 43%
• KEY DISEASE CHARACTERISTICS: All groups were primarily patients with lung disease followed by head and neck and then ovarian cancer.
• OTHER KEY SAMPLE CHARACTERISTICS: All groups received cisplatin primarily with another emetogenic chemotherapy agent although patients were not eligible if they were due to receive moderately or highly emetogenic chemotherapy on subsequent days. Karnofsky Performance Status Scale scores were primarily 90% among all groups, and the majority of group members reported no alcohol consumption.

• SITE: Multi-site    
• SETTING TYPE: Not specified    
• LOCATION: 29 sites in Russia, and 15 sites in Ukraine

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

Phase 2, multi-center, randomized, double-blind, double-dummy, parallel group

NEPA is better than palonosetron in treating chemotherapy-induced nausea and vomiting with the 300 mg dosing showing consistently better outcomes than 200 mg and 100 mg dosing with no apparent safety issues. NEPA 300 mg had better outcomes in complete response, no emesis, no significant nausea, and complete protection in the acute, delayed, and overall phases when compared to PALO alone.

• Measurement/methods not well described
• Other limitations/explanation: Although the efficacy measurements were adequately described, there was a lack of detail regarding how safety was measured. Furthermore, not all of the safety measurements were reported in the results section (missing information about laboratory evaluations, vital signs, and physical exam findings). There were no reports of missing data.

At this time, NEPA is not approved by the FDA for use in CINV; however, it shows promising results in alleviating CINV in patients receiving highly emetogenic chemotherapy for cancer treatment. Nurses should be aware that NEPA 300 mg was superior to the NEPA 100 mg and 200 mg dose for alleviating CINV in all phases after chemotherapy.

To determine if a single 90-mg dose of casopitant added to ondansetron and dexamethasone would improve control of chemotherapy-induced nausea and vomiting (CINV) over 0–120 hours following initiation of oxaliplatin-based, moderately emetic chemotherapy (MEC) compared to ondansetron and dexamethasone alone and, as an optional component of the study, to measure the plasma concentration of 90 mg IV casopitant in patients enrolled in trials at various centers

Patients received 90 mg IV casopitant or IV placebo 30 minutes prior to oxaliplatin on day 1. All subjects received 8 mg IV dexamethasone and 8 mg ondansetron hydrochloride prior to starting the oxaiplatin on day 1, followed by five separate 8-mg doses at approximately 12-hour intervals on study days 1 to 3. Patients recorded efficacy data for the subsequent 120 hours.

To assess PK profiles, blood samples were obtained during cycle 1 of chemotherapy at the following times: predose, end of infusion, and 0.5, 1, 3, 5, 8, 12, 16, and 24 hours after infusion. A final sample was taken between 30 and 48 hours after infusion.

• The study reported on 707 patients.
• Mean age was 61 years old.
• The placebo arm was 59% male and 41% female.
• The casopitant arm was 51% male and 49% female.
• Patients had been diagnosed with colorectal cancer and were receiving oxaliplatin doses between 85 and 130 mg/m² in their first cycle of therapy.

This was a multi-site study conducted at multiple settings at 89 centers (hospitals or outpatient clinics) in 11 countries.

• All patients were in active antitumor treatment.
• This study has application to elder care.

This was a phase III, multicenter, randomized, double-blind, active-controlled, two-arm, parallel-group study.

• Patients recorded the number of emetic episodes, the number of nausea episodes, and use of rescue medication in study diaries during the 120-hour assessment phase.
• Patients completed the Functional Living Index–Emesis (FLIE) and used a visual analog scale (VAS) to rate nausea.
• Blood samples were used to assess PK profiles.

No difference in the rate of CR was noted in the casopitant group compared to the placebo group for the overall (placebo 85%, casopitant 86%, p = 0.7273), acute (placebo 96%, casopitant 97%), or delayed phases (placebo 85%, casopitant 86%). At 24 hours after 90 mg IV casopitant administration, the plasma casopitant concentration was 24% lower than the values noted in prior studies with 150 mg oral administration. Casopitant was well tolerated by patients.

The addition of single, 90-mg, IV dose of casopitant did not improve control of CINV at any time during 120 hours following initiation of oxaliplatin-based MEC. Excellent control of CINV was achieved in this study population with the combination of ondansetron and dexamethasone alone.

• Important differences existed in the baseline sample and groups.
• Key sample group differences could influence results.
• Findings are not generalizable.
• A difference in nausea was reported between the groups at baseline.

The results of this study indicate that ondansetron and dexamethasone are sufficient enough to control CINV associated with oxaliplatin chemotherapy in the treatment of patients with colorectal cancer. This finding is contrary to other studies, and the explanation is somewhat unclear. The PK concentration of the 90 mg IV casopitant was lower than that seen in the oral casopitant. A direct comparison of the IV regimen and the oral regimen in combination with ondansetron and dexamethasone in this patient population is warranted, as this is a large oncology patient population.

To assess the effect of gender on treatment response for aprepitant plus a 5-HT₃ antagonist and corticosteroid for the prevention of chemotherapy-induced nausea and vomiting (CINV) 

The data from two phase III studies of aprepitant plus a 5-HT₃ antagonist and corticosteroid for the prevention of CINV were pooled. The two trials were of patients receiving more than 70 mg/m² of cisplatin randomly assigned to control regimen or aprepitant regimen. Patients were randomized to one of the treatment groups and stratified by gender. Patients used a diary to document emetic episodes, severity ratings of nausea (on a 100-mm horizontal visual analogue scale), and any use of rescue medications.

The study reported on 1,044 patients older than 18 years with a Karnofsky score greater than 60 and who were scheduled for first their cycle of chemotherapy, including cisplatin.

The studies were conducted in the United States and the Netherlands, predominately in university cancer centers.

Two identically designed, randomized, double-blind parallel group, placebo-controlled trials were reviewed.

Visual analogue scales (VASs) and patient diaries were used.

• In the control group, 41% of women had an overall complete response (CR) compared with 53% of men.
• In the aprepitant group, 66% of women had an overall CR compared with 69% of men.
• The enhanced efficacy of aprepitant regimen in women occurred during acute and delayed phases and resulted in similar rates of antiemetic control for men and women.
• The aprepitant regimen partly maintained improvement over multiple cycles for men and women.

The addition of aprepitant may reverse the risk of gender for CINV in women receiving highly emetogenic chemotherapy.

Details of design, primary efficacy, and tolerability are not included, but the results of the studies are published elsewhere.

To examine the efficacy of acupuncture in women with breast cancer experiencing hot flashes as a result of anti-estrogen medication

Patients were randomized to either 10 weeks of traditional Chinese acupuncture or sham acupuncture.

The trial reported on a sample of 59 women with breast cancer.

A prospective, controlled trial design was used.

• Mean number of hot flashes at day and night were recorded prior to treatment, during the treatment period, and during the 12 weeks following treatment.
• Kupperman Index was completed at baseline, at the end of the treatment period, and at 12 weeks following treatment.

During the treatment period, the mean number of hot flashes at day and night was significantly reduced by 50% and almost 60%, respectively, from baseline in the acupuncture group, and was further reduced by 30% both at day and night during the next 12 weeks. In the sham acupuncture group, a significant reduction of 25% in hot flashes at day was seen during treatment, but was reversed during the following 12 weeks. No reduction was seen in hot flashes at night. Kupperman Index was reduced by 44% from baseline to the end of the treatment period in the acupuncture group, and largely maintained 12 weeks after treatment ended. No corresponding changes were seen in the sham acupuncture group.

• A placebo effect may have occurred.
• The study had a small sample size.

Longer studies are needed to see if effect continues.

To evaluate the prophylactic use of a Safetac product, Mepitel Film, on moist desquamation rates

At the start of radiation treatment, the breast or chest wall was divided into medial and lateral halves, and sections were randomly assigned to treatment with either Mepitel Film or aqueous cream. Mepitel Film was applied at the start of radiation treatment by the research radiation therapist on either the entire lateral or the entire medial part of the breast or chest wall to be irradiated as randomly assigned, and aqueous cream was applied twice daily to the control area by the patients.

The date of onset and location of moist desquamation were recorded for each patient. Moist desquamation was treated according to the standard departmental protocol consisting of Mepilex Lite dressings. Mepitel Film was left on during radiation because it had been determined that the Film has a clinically insignificant bolus effect of 0.12 mm. Follow-up assessment was done up to four weeks after the completion of treatment.

• N = 78 included for analysis
• MEAN AGE = 59.9 years
• AGE RANGE = 30–94 years
• MALES: 2.56% (2 men), FEMALES: 97.44% (76 women)
• KEY DISEASE CHARACTERISTICS: Breast cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Most were of European ethnicity. Patients did not have concurrent chemotherapy. Most patients had 40–50 Gy in 15–25 fractions.

• SITE: Single center—University of Otago  
• SETTING TYPE: Clinic    
• LOCATION: New Zealand

• Phase-III, randomized trial
• Intrapatient, controlled, single-center trial

Skin reaction severity was assessed using the radiation-induced skin reaction assessment scale (RISRAS) and Radiation Therapy Oncology Group (RTOG) scales.

Overall skin reaction severity was reduced by 92% (p < 0.0001) in favor of Mepitel Film (RISRAS). All patients developed some form of reaction on cream-treated skin, which progressed to moist desquamation in 26% of patients (RTOG grades I: 28%, IIA: 46%, IIB: 18%, III: 8%). Only 44% of patients had a skin reaction under the Film, which did not progress to moist desquamation in any of the patients (RTOG grades I: 36%, IIA: 8%). No patients had moist desquamation with the Mepitel Film. No relationship existed between smoking, skin type, or other patient variables and skin toxicity results. Patients who received hypofractionation were less likely to develop moist desquamation than others (p = 0.012).

Mepilex Film was effective in preventing severe skin reactions.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• The Mepilex Film was in situ for days at a time
• Neither the research radiation therapist nor the patients were blinded to which skin area had been randomized to Mepilex Film and which to cream.

Mepital Film use may be an effective approach to prevent severe radiodermatitis in patients treated for breast cancer. Further research to confirm these findings in other patient groups is warranted.