To determine if oral melatonin administered at night would reduce fatigue and improve sleep in patients with advanced cancer treated in a palliative care facility

This was a two-part trial. In part one, patients received either melatonin (20 mg) or placebo followed by a washout of two days, then crossed over and received the opposite of the first week of treatment. Part two was an open-label study of patients who completed part one and chose to continue melatonin. Study questionnaires were completed at the beginning and end of each treatment period (days 1, 7 ,10, and 17). In part two, study measures were obtained weekly. Patients were randomly assigned to the order in which they received melatonin or placebo.

• N = 34 by ITT analysis  
• MEAN AGE = 64.5 years
• AGE RANGE = 35–84 years
• MALES: 38%, FEMALES: 62%
• KEY DISEASE CHARACTERISTICS: Breast and lung cancer were most common. All had advanced disease.

• SITE: Single site  
• SETTING TYPE: Inpatient  
• LOCATION: Denmark

• PHASE OF CARE: Active antitumor treatment

• Randomized, placebo-controlled, crossover trial

• Multidimensional Fatigue Inventory (MFI)
• EORTC Cancer Quality of Life Core 15 for palliative care patients (EORTC-QLQ-C15-PAL)

No significant differences were noted in patient outcomes between the placebo and melatonin groups.

Melatonin administration did not improve fatigue, insomnia, or other symptoms in patients with advanced cancer.

• Small sample (less than 100)
• Subject withdrawals 10% or greater
• Multiple and frequent use of the same measurement tools

This study did not show any improvement in fatigue or sleep as a result of melatonin.

Patients smeared 20 mL of pure, natural honey (acidic with a pH of about 3.9) on the inside of their mouths 15 minutes before, 15 minutes after, and six hours after radiation. Patients rinsed honey on oral mucosa and then swallowed it slowly. Patients were randomized to the treatment or control group. Patients also used benzydamine HCL plus supportive oral care measures. A solubility-reducing factor present in honey can activate in the absence of saliva.

• N (experimental group) = 20
• N (control group) = 20
• KEY DISEASE CHARACTERISTICS: Patients with head and neck cancer receiving chemotherapy and radiotherapy
• OTHER KEY SAMPLE CHARACTERISTICS: Radiation dose of 60–66 Gy; chemotherapy: cisplatin 20 mg/m² once a week before radiotherapy

• April 2005–July 2006

• World Health Organization

• Treatment group: No patients developed grade 4 mucositis, and only three (15%) developed grade 3 mucositis.
• Control group: Three patients (15%) developed grade 4 mucositis, and nine (45%) developed grade 3 mucositis.
• Stated as significant, but value not given
• Five patients in the control group had therapy interrupted.
   

• Small sample
• Did not give p values for differences in mucositis
   

• Easy to use
• Cost-effective
• Pleasant

This trial randomized patients to two arms: one group received fluoxetine, and the other group received placebo for five weeks.

Patients with cancer (N = 115) were randomized to two arms: fluoxetine treatment (n = 45) versus placebo (n = 46) for five weeks.

A randomized, controlled, double-blinded trial design was used.

• Hospital Anxiety and Depression Scale (HADS)
• Symptom Checklist–90–Revised (SCL90-R)
• Montgomery-Åsberg Depression Rating Scale (MADRS)
• Hamilton Anxiety Scale (HAS)
• Spitzer Quality of Life Index (SQOLI)

Response rate (HADS) score < 8 after five weeks was not significantly higher in the fluoxetine group compared to the placebo group. There was significant decrease in mean scores on the SCL90-R in the fluoxetine group. There was no difference between groups on MADRS, HAS, or SQOLI.

Lower scores on subscales of the SQL90-R may reflect changes in anxiety levels between groups.

The authors did not mention power of effect size.

To determine the efficacy and safety of increasing opioid doses versus increasing doses of an adjuvant for patients with definite neuropathic cancer pain (i.e., neuropathic pain that occurred as a result of the disease, the treatment, or both). The goal was to achieve a 30% or more decrease in the visual analog scale (VAS) score compared to baseline.

One hundred and twenty patients were divided via simple randomization into two groups. Baseline data were collected on all 120 patients (i.e., VAS score, meds, and full assessment). The first group was prescribed a starting dose of pregabalin at 75 mg per day and titrated up by 75 mg every third day as needed up to 600 mg per day divided into two doses, until adequate pain relief was achieved or adverse effects were noted. The second group was given 25 mcg per hour fentanyl patch and increased by 25 mcg per hour every 72 hours up to a max dose of 150 mcg per hour until adequate pain relief was achieved or adverse events were noted. Both groups had rescue oral morphine as needed.

• N = 120  
• AGE = Older than 18 years
• MEAN AGE = Pregabalin group: 61.2 years (SD = 9.3 years); fentanyl group: 63.2 years (SD = 11.8 years)
• MALES = 58, FEMALES = 62
• KEY DISEASE CHARACTERISTICS: Diagnosed with definite neuropathic cancer pain
• OTHER KEY SAMPLE CHARACTERISTICS: On second step of the World Health Organization analgesic ladder; resistant to a combination of codeine with paracetamol; a non-steroidal anti-inflammatory drug and methylprednisolone used for a minimum of three consecutive days; expected survival of two months or longer; normal renal function and a VAS score greater than 4 at baseline

• SITE: Single site   
• SETTING TYPE: Not specified   
• LOCATION: Athens, Greece

• PHASE OF CARE: Mutliple phases of care
• APPLICATIONS: Elder care, palliative care

• Prospective, head-to-head, comparative, randomized, open-label

• Satisfaction Criterion (created by the authors for this study), which intended to define the level of pain relief considered appropriate for the study patients
•  VAS

Changes in VAS scores showed no difference between groups, but the percentage change in these scores showed a significant reduction for the patients on pregabalin (-58% versus -50%). A greater percentage of patients on pregabalin achieved the study primary endpoint of at least a 30% reduction in pain VAS score (73.3% with pregabalin, 36.7% with fentanyl, p < .0001). No significant difference was seen in the proportion of patients needing rescue medication.

For these patients with neuropathic pain, no significant differences were seen in efficacy of adjuvant pregabalin versus increasing opioid medication for pain control.

• Authors created their own measurement tool.
• Baseline VAS analysis was different between the two groups, with baseline  median pain lower in the opioid group—this could have made the defined reduction easier.
• Short timeframe (four weeks)
• The interventions compared involved two different routes of medication administration.
• The dose limit on fentanyl (150 mcg per hour) was based on the groups’ pain center protocol, which dictates that patients on more than 150 mcg per hour fentanyl would need to be considered for a different treatment or intervention.
• Limited information on any adverse events experienced by study participants
• No information about the amount of rescue medication used in both groups, only the proportion of patients that used any rescue medication

I find the results of this study to be useful for oncology professionals working with patients with neuropathic cancer pain, whether from the disease, the treatment, or both. A similar study using tramadol versus pregabalin for neuropathic cancer pain may be of value.

To evaluate the effects of 24 weeks of donepezil versus placebo on objectively measured cognitive function starting at least six months after whole- or partial-brain irradiation

This clinical trial tested donepezil at 5 mg daily for six weeks followed by 10 mg daily for 18 weeks compared to a placebo. Study outcome measurements were collected before randomization, and 12 and 24 weeks after randomization.

• N = 146
• MEDIAN AGE = 55 years (range = 20–84 years)
• MALES: 50%, FEMALES: 50%
• KEY DISEASE CHARACTERISTICS: 68% primary brain tumor (primary diagnosis was glioblastoma multiforme); 26% brain metastases from other primary tumor (primary diagnosis was lung cancer); 6% prophylactic cranial irradiation; 35% primarily frontal lobe involvement; median time since diagnosis was 40 months
• OTHER KEY SAMPLE CHARACTERISTICS: Pretreatment sample characteristics did not differ between groups. Most participants were married, white, had some college education, and had Eastern Cooperative Oncology Group scores of 0–1. Retention at the end of the trial was 74%, which did not differ between groups. Participants who dropped out had less education, lower income, smaller brain volume, and more hippocampal involvement.

• SITE: Multi-site
• SETTING TYPE: Outpatient
• LOCATION: Winston-Salem, NC, and Houston, TX

PHASE OF CARE: Late effects and survivorship

Randomized, double-blinded, placebo-controlled trial

• Hopkins Verbal Learning Test–Revised (HVLT-R)
• Modified Rey-Osterrieth Complex Figure
• Trail Making Test (TMT) parts A and B
• Controlled Oral Word Association Test (COWAT)
• Digit Span Test
• Grooved Pegboard Test

Self-reported adherence to the dose was approximately 92%, which did not differ between groups. The donepezil group reported more diarrhea (25%, p = 0.005) than the control. At baseline, both groups had poorer verbal memory, motor speed and dexterity, attention, and executive function compared to population norms. There was no improvement in overall cognitive function with 24 weeks of donepezil, but improvements were found for individual measures of memory (p = 0.007, 0.027) and motor speed and dexterity (p = 0.016). Donepezil showed greater improvement in overall cognitive function for patients with poorer cognitive function at baseline (p = 0.01).

For patients who received whole or partial brain irradiation, 24 weeks of donepezil improved memory and motor and speed dexterity. Greater improvements in multiple cognitive domains, including significant improvement in overall cognitive function, were found for patients with poorer cognitive function at baseline.

• Subject withdrawals ≥ 10%
• Most participants were white.

For patients who receive partial- or whole-brain irradiation for primary brain tumors or brain metastases, donepezil may improve memory and motor speed and dexterity. Patients with poorer cognitive function may have greater benefit, including improvement in overall cognitive function. Educate patients about the risk for diarrhea and appropriate management.

To assess the safety and efficacy of 180 mg rolapitant for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with cancer who receive moderately or highly emetogenic chemotherapy (HEC)

Patients who had a KPS of 60 or higher, were expected to live at least four months, and had adequate bone marrow and liver and kidney function were randomly assigned to receive 180 mg of rolapitant versus placebo, which looked exactly like the rolapitant.

• N = 1,087 (from two identically designed global studies)
• MEAN AGE = 58.8 years
• MALES: 63%, FEMALES: 37%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS Most common primary tumor was lung (44%), followed by head and neck (18%)
• OTHER KEY SAMPLE CHARACTERISTICS: Patients who had a KPS of 60 or higher, were expected to live at least four months, and had adequate bone marrow and liver and kidney function

• SITE: Multi-site   
• SETTING TYPE: Multiple settings    
• LOCATION: International study

PHASE OF CARE: Active antitumor treatment

This article describes two randomized, double-blind, active-control studies.

In both studies (and in the pooled results), treatment with rolapitant resulted in a significantly increased number of patients experiencing a complete response in the delayed phase. The pooled studies found significant difference in the acute phase (first 24 hours). In the overall phase, complete response was significantly more frequent in the first study and in the results of the pooled studies. No significant differences were observed between study groups with respect to daily living as measured by the FLI-E questionnaire.

Oral rolapitant taken once daily before chemotherapy in combination with a 5-HT₃ receptor antagonist and dexamethasone is superior to 5-HT₃ receptor antagonist and corticosteroid alone.

The study participants were enrolled prior to recommendations for the addition of an NK₁ receptor antagonist to standard care and the use of dexamethasone to HEC.

As now accepted, the addition of an NK₁ receptor antagonist reduces CINV experienced by patients receiving HEC. Patient education regarding adherence to medications and correct timing can help them prevent what is often the most worrisome side effect.

To determine the efficacy, safety, and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy (MEC) regimens and to determine if aprepitant would provide a complete response at preventing CINV in the first 5 days (120 hours) following chemotherapy

Patients naïve to moderately or highly emetogenic chemotherapy (HEC) and scheduled to receive a single dose of MEC agent, were enrolled in the study. Group one received an aprepitant triple-therapy regimen; group two received a control regimen that included a placebo 1 hour prior to chemotherapy, ondansetron (same dosing as aprepitant group), and dexamethasone on day 1, and, on days 2 and 3, placebo once daily and ondansetron twice daily (by mouth).

• The study looked at 848 participants.
• The mean age in years for patients receiving the aprepitant regimen was 57.1 (SD = 11.8 years); the mean age for patients receiving the control regimen was 55.9 (SD = 12.6 years).
• Diagnoses were 52% breast, 20% colon, 13% lung, and 4.6% ovarian.
• Chemotherapy regimens were 52% nonanthracycline/cyclophosphamide (n = 441) and 48% anthracycline/ cyclophosphamide (n = 407).
• More than two-thirds (69%) of participants were white.
• History of motion sickness was present in 5.6% of the aprepitant group and 9.8% of the control group.
• History of vomiting during pregnancy was present in 14.2% of the aprepitant group and 17.9% of the control group.

Studies were conducted at multiple sites in the United States, Mexico, Canada, Chile, Brazil, Peru, Colombia, Panama, Hong Kong, Australia, South Africa, France, Germany, Israel, and Russia.

Patients were in active treatment.

The study was a phase III, prospective, randomized, gender-stratified, double-blind trial.

Patients recorded the time and date of nausea, retching, and vomiting episodes in diaries. Nausea was assessed daily using a 100-mm horizontal visual analogue scale (VAS). If a rescue drug was used, the drug name and date and time of administration was recorded. Common Terminology of Adverse Events, version 3.0 (CTAE v 3.0) was used to assign toxicity grades to all laboratory test results and adverse events.

• The proportion of patients reporting no vomiting during the five days (0–120 hours) following initiation of chemotherapy was significantly higher in the aprepitant group (p < 0.001).
• In both the acute and delayed phases, significantly more patients in the aprepitant group reported no vomiting compared to the control group (p < 0.001).
• More patients in the aprepitant group reported a complete response in both the acute and delayed phases (p < 0.001), and time to first vomit was longer.
• No significant differences in the reporting of adverse events were found between groups.

The aprepitant regimen provided significantly more vomiting-free time. Better control with an aprepitant–containing, triple antiemetic regimen was seen for those receiving MEC (nonanthracycline and cyclophosphamide [AC] or AC).

• Results presented were for cycle one only.
• Limited generalizability is possible because the majority of the sample was female (77%) and Caucasian (69%).

Aprepitant was effective in preventing chemotherapy-associated vomiting in patients receiving a broad range of MEC and should be considered as part of a standard antiemetic regimen.

To evaluate the safety and efficacy of four different doses of rolapitant for the prevention of chemotherapy-induced nausea and vomiting (CINV) associated with cisplatin-based, highly emetogenic chemotherapy

Eligible patients were randomized to receive rolapitant at 9, 22.5, 90 or 180 mg or no rolapitant (active control) administered two hours before the first dose of chemotherapy on day 1 of cycle 1 with cisplatin greater than 70 mg/m². Patients also received Zofran^® at 32 mg IV and Decadron^® at 20 mg orally 30 minutes before chemotherapy. Dexamethasone was administered at 8 mg orally twice daily on days 2, 3, and 4.

• N = 454  
• MEDIAN AGE = 55 years (range = 18–86 years)
• MALES: 244 (54%), FEMALES: 210 (46%)
• KEY DISEASE CHARACTERISTICS: No disease characteristics were provided. Patients were receiving highly-emetogenic chemotherapy at 70 mg/m².
• OTHER KEY SAMPLE CHARACTERISTICS: Exclusions included patients who had previously received cisplatin, 5HT3 antagonists, NK1 antagonists, or other drugs that may interfere with the study five days prior to treatment. Patients who had abdominal or pelvis radiation scheduled on day 5 or 6 or were receiving systemic corticosteroids also were excluded.

• SITE: Multi-site    
• SETTING TYPE: Not specified    
• LOCATION: Seventy-five sites in 21 countries

• PHASE OF CARE: Active antitumor treatment

Phase 2, randomized, double-blinded, active-controlled, parallel-group, dose-ranging study

• Patient diary with Visual Analog Scale (VAS) for nausea, emesis episodes, and use of rescue medication
• Functional Living Index-Emesis (FLIE) for quality of life
• Laboratory values, vital signs, electrocardiograms, and physical examinations for safety and tolerability

Rolapitant was well tolerated and was associated with greater complete response rates than the placebo group. Rolapitant at 180 mg achieved a statistically significant improvement compared to the active control group in the acute (87.6% and 66.7%, respectively, p = 0.001) and delayed (63.6% and 48.9%, respectively, p = 0.045) phases. Complete response rates across all phases of CINV were consistently higher for all other rolapitant dose groups compared to the active control group except the 9 mg group in the acute phase. However, this did not achieve statistical significance. Rolapitant also was statistically superior to the active control in other key secondary efficacy variables including less emesis in the acute and delayed phases and less nausea in the acute and delayed phases. Rolapitant at 90 and 180 mg doses significantly improved quality of life compared to the control group. The incidence of serious adverse events was similar in all treatment groups.

All doses of rolapitant were well tolerated and were associated with greater compete response rates than the active control (except 9 mg in the acute phase). Rolapitant at 180 mg demonstrated a clinical statistically significant effect in preventing CINV in the overall, acute, and delayed phases for patients receiving highly emetogenic chemotherapy.

In this study, rolapitant at 180 mg was safe, well tolerated, and effective in controlling CINV in all phases when given in combination with dexamethasone and a 5HT3 receptor antagonist for patients receiving highly emetogenic chemotherapy.

To explore the efficacy and safety of rolapitant in preventing chemotherapy-induced nausea and vomiting (CINV) over multiple cycles of moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC)

Patients were stratified by gender to receive either 180 mg oral rolapitant or placebo approximately 1–2 hours before receiving either MEC or HEC. All patients received a 5-HT₃ antiemetic and dexamethasone. Patients receiving MEC were given 2 mg oral granisetron on days 1–3 and 20 mg dexamethasone on day 1. Patients receiving HEC (e.g., cisplatin-based chemotherapy) were given 10 mc/kg granisetron intravenously and oral 20 mg dexamethasone on day 1 and 8 mg twice daily on days 2–4. Patients receiving taxanes were given dexamethasone per the package insert.

• N = 1,998   
• AGE RANGE = 18–90 years
• MEAN AGE = 57 years
• MALES: 38.4% (intervention arm), 36.9% (control arm); FEMALES: 61.6% (intervention arm), 63.1% (control arm)
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Patients were not recruited or stratified by specific tumor type. More than half of the patients (67%) had breast cancer.
• OTHER KEY SAMPLE CHARACTERISTICS: Inclusion criteria required that patients be aged 18 or older, have a Karnofsky score of 60 or better, have a life expectancy of four months or longer, and have adequate bone marrow, liver, and kidney functions. Patients in the MEC group were required to be naïve to MEC or HEC and scheduled to receive their first course of IV cyclophosphamide (< 1500 mg/m²), doxorubicin, epirubicin, carboplatin, idarubicin, ifosfamide, irinotecan, daunorubicin, and/or IV cytarabine (> 1 g/m²). At least 50% of the patients were to receive an AC-based (doxorubicin and cyclophosphamide) regimen. Patients in the HEC arm were required to be naïve to cisplatin and scheduled to receive their first course of cisplatin-based chemotherapy.

• SITE: Multi-site   
• SETTING TYPE: Not specified    
• LOCATION: Multinational—North, Central, and South America; Europe; Asia; and Africa

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

• Global, randomized, double-blind, placebo-controlled studies

Patients were given a diary to record all episodes of nausea, vomiting, and use of rescue drugs for five days post chemotherapy administration during cycle 1. For subsequent cycles, patients were asked two CINV assessment questions on days 6–8: (a) Have you had any episodes of vomiting or retching since your chemotherapy started in this cycle? and (b) Have you had any nausea since your chemotherapy started in this cycle that interfered with normal daily life? Assessments of safety variables, such as adverse events, vital signs, physical and neurological exams, electrocardiograms, and clinical lab values, were assessed during all cycles.

Compared to the control group, more patients receiving rolapitant reported no emesis or interfering nausea in cycles 2 (p = 0.006), 3 (p < 0.001), 4 (p = 0.001), and 5 (p = 0.021) when compared to the control group. Time to first emesis was significantly longer for the rolapitant group in cycles 1–6 (p < 0.001). The incidence of treatment-related adverse events were only slightly lower in the rolapitant (5.5%) than the control group (6.8%) during cycles 2–6.

Oral rolapitant was effective in protecting against CINV over multiple cycles of MEC and HEC. Rolapitant was well tolerated and demonstrated no increased frequency of adverse effects and no cumulative toxicity over multiple cycles.

Women were disproportionately high in the MEC study largely because of the high number of patients with breast cancer receiving AC chemotherapy.

The findings support the possible benefits of adding rolapitant to the therapy of patients receiving MEC and HEC.

To evaluate if Caphosol™ is effective to treat oral mucositis (OM) in pediatric patients who received chemotherapy or hematopoietic stem cell transplant (HSCT)

A sample of 33 patients between 4–18 years old was assigned to Caphosol or placebo. All patients received standard local supportive care, in addition to Caphosol study or 0.9% sodium chloride (NaCl) placebo mouth rinse. All patients were instructed to use the study mouthwash four times daily during their OM period. Primary study outcome was defined as the number of days with OM greater than grade 1. Secondary outcomes were pain and analgesic use.

• N = 29
• AGE RANGE: 4–18 years
• MALES: 66%, FEMALES: 34%
• KEY DISEASE CHARACTERISTICS: Patients had been diagnosed with hematologic malignancies, solid tumor, and benign hematologic disorders and were receiving chemotherapy or HSCT.

• SITE: Multi-site
• SETTING TYPE: Inpatient
• LOCATION: Four university hospitals in the Netherlands

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

• Double-blinded, placebo-controlled trial

• The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0 mucositis scoring system was used to evaluate mucositis.
  • Days of mucositis greater than grade 1 and peak level of mucositis
  • Days of pain and peak of level pain
  • Days of analgesic use, morphine use, peak dose (mg/kg)
  • Need for tube feeding and number of days
  • Need for parenteral feeding and number of days
  • Blood cultures taken

Chi-square or t-test was used for analysis. The number of days with mucositis greater than grade 1 did not differ significantly between the two study groups (p = 0.154). No significant differences were found between Caphosol and placebo for all the outcome measures except days of pain and tube feeding requirement. Placebo was associated with significantly fewer days of pain (p = 0.035) . The need for tube feeding was significantly higher in the Caphosol group.

Therapeutic use of Caphosol was not beneficial in the treatment of pediatric patients with cancer therapy-induced OM.

• Small sample (< 30)
• Risk of bias (sample characteristics)
• Key sample group differences could influence results.
• Findings not generalizable
• High grades of mucositis were found at the start of the study with 64.3 % of the placebo group versus 33.3 % of the patients with Caphosol having greater than grade 1 mucositis at the start of the study (p = 0.143). The placebo group also showed a trend of shorter mucositis duration, which may suggest that mucositis was more advanced at baseline and resolved earlier. This, in turn, may have contributed to the finding that the placebo group had fewer days with mucositis greater than grade 1.
• A problem was seen with a power calculation, and many analyses failed to demonstrate significant results. This study has significant risk for type II errors. In addition, this study included various types of cancer and cancer treatments, which may have contributed to the lack of significance in findings.

Although this study was a double-blind, randomized, controlled trial, the significantly small sample size was problematic. The authors concluded that Caphosol was not effective in practice; however, it is not conclusive because of the significantly high risk for type II errors. A study with a larger sample size is required to assess the efficacy of Caphosol.