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.

To determine if acetyl-L-carnitine (ALC) prevents chemotherapy-induced peripheral neuropathy (CIPN) in women with early stage breast cancer receiving taxane-based treatment

Patients were randomly assigned to receive either placebo or ALC 3,000 mg (6 capsules) daily for 24 weeks.

• N = 409 (final sample); 208 received ALC and 201 received placebo
• MEDIAN AGE = 51 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Women with stage I-II breast cancer who were to receive adjuvant taxane therapy

• SITE: Multi-site 
• SETTING TYPE: Outpatient

PHASE OF CARE: Active antitumor treatment

Randomized, double-blind, placebo-controlled

• Neurotoxicity component of the Functional Assessment of Cancer Therapy–Taxane scale (FACT-NTX)
• Functional Assessment of Cancer Therapy–Taxane Trial Outcome Index (FACT-TOI)
• Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-Fatigue)

At week 12,  patients taking ALC had lower FACT-NTX scores (0.9), indicating more CIPN than those taking placebo (P = .17). After 24 weeks, patients taking ALC had a greater than 5-point decrease in FACT-NTX scores (P = .05). The FACT-TOI scores were lower with ALC (P = .03 ). There was no difference in the FACIT-Fatigue score between arms. Patients reported grade 3-4 neuropathy in the ALC arm versus grade 1 reported in the placebo arm resulting from taxane (P = .46).

At the end of 24 weeks, patients who had been taking ALC reported an increase in CIPN and a decrease in function, compared to those taking placebo.

• Subject withdrawals were ≥ 10%.
• Since this study was done with a taxane-based chemotherapy, it is unknown how other neurotoxic drugs given with ALC would influence CIPN.
• The scores at 24 weeks represented the main secondary endpoint and not the primary endpoint; however, since not all patients had completed the taxane treatment at 12 weeks from when they were registered, 24 weeks may have been the most appropriate endpoint after all.
• Since this trial indicated a detrimental effect with ALC and a taxane, it is recommended that a taxane-based chemotherapy and ALC trial not be repeated.

It has been reported in the literature that many patients take supplements without any evidence of efficacy. Patients often have discussions with nurses and ask questions about the use of supplements. To give patients correct information, including the risks, nurses need to be knowledgeable about the efficacy of nutritional supplements. It is recommended, from the results of this study, that nurses discourage patients from taking ALC since it may be harmful.

STUDY PURPOSE: To provide evidence-based guidance on optimum prevention and treatment approaches in the management of chemotherapy-induced peripheral neuropathy in adult cancer survivors

TYPE OF STUDY: Systematic review

DATABASES USED: Ovid Medline (1946–April, week 2, 2013); EMBASE (1980–2013, week 16); AMED Allied and Complementary Medicine (1985–April 2013)

KEYWORDS: chemotherapy-induced peripheral neuropathy; adult cancer survivors; randomized clinical trials

INCLUSION CRITERIA: Adult cancer survivors with chemotherapy-induced peripheral neuropathy; randomized trials

EXCLUSION CRITERIA: Phase 1 trials; published in a language other than English; less than 10 patients; focused on radiation or stem cell transplant neuropathy; animal studies

TOTAL REFERENCES RETRIEVED = 1,252

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: An expert panel representing neurology, nursing, medical oncology, community oncology, pain research, and genetics met through teleconference and emails to review and develop the American Society of Clinical Oncology guidelines.

• FINAL NUMBER STUDIES INCLUDED = 48
• TOTAL PATIENTS INCLUDED IN REVIEW: Treatment studies: 780; prevention studies: 3,741

PHASE OF CARE: Active antitumor treatment

Forty-two randomized clinical trials involved 19 various interventions for prevention of chemotherapy-induced peripheral neuropathy. These agents included anticonvulsants, antidepressants, vitamins, minerals, and other chemoprotectant drugs. Only six randomized clinical trials discovered six different drugs, such as antidepressants, anticonvulsants, and a topical gel, for the prevention of chemotherapy-induced peripheral neuropathy. The following are not recommended for use: acetyl-l-carnitine, amifostine, amitriptyline, calcium and magnesium, glutathione, nimodipine, ORG 2766, trans retinoic acid, rhuLIF, and vitamin E. Venlafaxine is not recommended for routine use in clinical practice. Although data support potential utility, evidence is not strong enough to suggest use. For treatment of chemotherapy-induced peripheral neuropathy, clinicians can offer duloxetine. No recommendation is made regarding ALC. Tricyclic antidepressants or gabapentin through trial use may be reasonable.  The panel felt that trying topical gel containing baclofen, amitriptyline, and ketamine would be reasonable. 

No agents were recommended for the prevention of chemotherapy-induced peripheral neuropathy, but duloxetine is moderately recommended for the treatment of chemotherapy-induce peripheral neuropathy. Even though conclusive evidence is lacking to recommend tricyclic antidepressants such as nortriptyline, gabapentin, and a topical gel containing baclofen,amitriptyline, and ketamine for treatment of chemotherapy-induced peripheral neuropathy, the expert panel agreed that offering these agents based on treatment for neuropathic pain is reasonable. The panel also recommended that patients be counseled regarding the lack of evidence in treating chemotherapy-induced peripheral neuropathy with these agents.

• Small, insufficient sample
• Inability to compare studies because of different outcomes
• Measurements and instruments used at different points in treatment

Nurses are at the frontline in assessing patients who are receiving agents with the potential for chemotherapy-induced peripheral neuropathy. Nurses should be aware of the standard of care in treating this population. Many drugs prescribed have no evidence in preventing or treating these patients. However, with these American Society of Clinical Oncology guidelines, a role for duloxetine is clear and a role for tricyclic antidepressants is possible. Nurses need to be knowledgeable about this information to better inform patients.

To determine if omega 3 fatty acids can be effective in decreasing arthralgia resulting from aromatase inhibitor (AI) treatment

Patients were randomized to receive either a placebo or 3.3 g of omega 3 fatty acids daily for 24 weeks. Random assignment was stratified by prior history of arthritis and prior taxane use. Study assessments were done at baseline and at six, 12, and 24 weeks.

• N = 209  
• MEDIAN AGE = 59.2 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Patients with stage 1 and 2 hormone-sensitive breast cancer receiving adjuvant AI therapy 
• OTHER KEY SAMPLE CHARACTERISTICS: Pain score greater than 5 out of 10 associated with AI use; median of 1.2 years of AI treatment

• SITE: Multi-site  
• SETTING TYPE: Outpatient    
• LOCATION: United States

• PHASE OF CARE: Active antitumor treatment

Double-blinded, placebo-controlled, randomized trial

• Brief Pain Inventory Short Form (BPI-SF)
• Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)
• Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hand (M-SACRAH)
• Functional Assessment of Cancer Therapy (FACT) Endocrine Symptoms
• Serum lipids and C reactive protein

There were no significant differences between the groups in worst pain scores or stiffness at any study time point. The mean observed changes in other study measures showed somewhat reduced symptoms in the omega 3 arm, but these changes were not statistically significant. There were no significant changes in serum measures over time other than decreased triglycerides in those receiving the fatty acids. Over time, symptoms improved in both study groups.

This study did not show any improvements in arthralgia symptoms induced by AIs with the use of omega 3 fatty acids compared to a placebo.

There are no effective therapies for the prevention or treatment of AI-associated arthralgia. Ongoing research to determine optimal approaches to prevent or manage this symptom is necessary. These symptoms' mechanism of development is not clear, but they may have inflammatory and autoimmune components.