To evaluate the efficacy of sublingual fentanyl orally disintegrating tablets (ODT) on breakthrough cancer pain; to assess the safety of sublingual fentanyl ODT and its impact on quality of life

Investigators followed patients through a 28-day observation period. Patients self-administered sublingual fentanyl ODTs on an as-needed basis for breakthrough pain episodes. The initial dose was determined by the clinician on the basis of previous treatment; the clinician titrated the dose as necessary. Patients used a questionnaire to record maximum breakthrough pain intensity, time to first effect, and time to maximum effect. Patients who had previously used breakthrough pain medication rated the effectiveness of the sublingual fentanyl ODTs in regard to speed, strength, and duration of action. During clinic visits on days 3, 7, 14, and 28, clinicians observed and recorded data about adverse events. Clinicians recorded measures of pain intensity at baseline and after 3, 7, and 14 days. Clinicians obtained anxiety and quality-of-life measures at baseline and at the end of the study.

• The sample was composed of 181 patients, and the study comprised 3,163 episodes of breakthrough pain.
• Mean patient age was 64.4 years. Age range was 35–89 years.
• Of all participants, 47.7% were female and 52.3% were male.
• Authors did not provide specific cancer-site information.
• At baseline, mean daily opioid use for background pain was 116.1 mg morphine equivalent. The range of daily opioid use for background pain was 60–240 mg.
• Mean pain intensity of background pain at baseline was 4.8. Mean number of breakthrough episodes was 2.7/day.
• The medications most commonly used for breakthrough pain were oral immediate-release liquid morphine, which 66% of patients used; oral transmucosal fentanyl citrate, which 13.2% of patients used; and oral immediate-release liquid hydromorphone, which 9.4% of patients used.

• Multisite
• Outpatient
• Germany

Prospective trial

• Numeric scale (0–10), to measure pain intensity
• Questionnaire, to measure breakthrough pain intensity maximum, time to first effect, and time to maximum effect
• Seven-point scale, to measure effect of study drug compared to that of previous medication in regard to speed of action, strength of action, duration of action, tolerability, and ease of handling
• Hospital Anxiety and Depression Scale (HADS)
• Modified Pain Disability Index (PDI)

With the study drug, breakthrough pain decreased signficantly (p < 0.00001), with mean pain intensity changing from 7.8 at baseline to 2.6. Patients reported that time to first effect was 10 minutes or less in 82.8% of episodes, less than 2 minutes in 19.4% episodes, and 2–5 minutes in 48.3% of episodes. Time to maximum effect was 30 minutes or less in 63.2% of episodes. In 83 patients who had previously used other medications for breakthrough pain, 87.7% said the study drug was better in speed of action; 85.7%, strength of action; 83.9%, duration of action; 88.6%, tolerability; and 87.3%, ease of handling. PDI scores decreased during the study (p < 0.0001). Prevalence of abnormal HADS scores declined. In regard to anxiety, 54.5% had abnormal scores at baseline; 1.6% had abnormal scores at the end of the study (p < 0.0001). In regard to depression, 70.3% had abnormal scores at baseline; 15.6% had abnormal scores at the end of the study (p < 0.0001). Mean dose per episode during the study was 400 mcg; dose range was 100–1600 mcg. Of all patients, 5.5% experienced at least one drug-related adverse event. The most common adverse events were nausea, somnolence, dizziness, and vomiting. At the end of the study, 84% of patients chose to continue taking sublingual fentanyl ODT.

Sublingual fentanyl ODT was effective in the treatment of breakthrough cancer pain. The drug had an acceptable safety profile and was associated with improvement in symptoms of anxiety and depression and improvement in pain-related disability scores.

• The study had a risk of bias due to no appropriate control group.
• Patients' recollection of experience with previous medications was the only basis of comparison regarding efficacy.
• Authors provide no information about missing data or patients' adherence to instructions about completing measurement assessments.
• Authors provide minimal demographic information about the sample.

Sublingual fentanyl ODT was a very effective and fast-acting treatment for breakthrough cancer pain. This drug appears to be an important addition to options for the management of breakthrough pain.

To determine the effectiveness of using antifungal therapy in conjunction with the diagnostic driven approach (DDA) in the management of invasive fungal infection (IFI) among patients undergoing allogeneic bone marrow transplantation (BMT)

Two strategies, DDA and antifungal prophylaxis, were used to diagnose and treat early IFI among allogeneic BMT patients. Two segments of 20 months included a preimplementation period in which medical records and laboratory statistics were used from admission up to six months. The intervention was the implementation of a DDA and the provision of antifungal prophylaxis. Prior to implementation, no routine antifungal prophylaxis was administered and the diagnosis of IFI was based on European Organization for Research and Treatment of Cancer (EORTC) criteria, including galactomannan assays. Antifungal agents were administered based on assay results. With the implementation of a new protocol, antifungal prophylaxis was given to those with graft-versus-host disease (GVHD), those treated with corticosteroid therapy, those with severe aplastic anemia, those undergoing cord blood transplantation, and those in which the standard diagnostic workup was deemed to be less effective. All patients were managed in high-efficiency particulate air (HEPA)-filtered rooms and housed in areas with limited access.

• N = 130   
• AGE = 35–45 years
• MALES: 38%, FEMALES: 28%
• CURRENT TREATMENT: Other
• KEY DISEASE CHARACTERISTICS: Malignant and benign, severe aplastic anemia
• OTHER KEY SAMPLE CHARACTERISTICS: Conditioning regimen (myeloablative or nonmyeloablative), presence of graft-versus-host disease (GVHD), neutropenia phase of absolute neutrophil count [ANC] < 500, and survival rates of three and six months. All had allogeneic hematopoietic stem cell transplantation (HSCT).

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: Referral center for HSCT (Hadassah Medical Center), Israel

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

• Pre-post design in which two periods pre intervention and post intervention segments were analyzed

• Breakthrough IFI (not specifically defined)
• Antifungal use
• Diagnostic test utilization

A significant reduction in the cases of IFI (p = 0.051) was observed overall. The incidence of mold infection (aspergillosis) decreased substantially in the protocol period (p = 0.054). However, no change was noted in the survival rates and breakthrough fungal infection in the pre and post intervention phases.

The implementation of a clinical management protocol helped diagnose and treat early fungal infection and was associated with an overall reduction in the incidence of IFI.

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Unintended interventions or applicable interventions not described that would influence results
• Drug toxicity level and poor oral acceptability of the medication
• No differentiation between individuals who received antifungals prior to the protocol period in comparing outcomes
• Comparison to a historical cohort with potential related threats to validity

Nursing role is vital in identifying the key sign and symptoms of infection and to highlight them to decrease the rates of fungal infections, hence minimizing the mortality and morbidity rates overall. This study demonstrated that a standardized approach to prophylaxis was associated with reduced fungal infections.

To evaluate the effectiveness of gabapentin in treating acute postoperative pain in patients who have undergone craniotomy

For anticonvulsant prophylaxis, patients were randomized to one of two groups. One group received 1200 mg oral gabapentin daily (400 mg three times/day). The other received 300 mg oral gabapentin daily (100 mg three times/day). Patients took medications for seven days before surgery, as part of the surgical regimen, and postoperatively. All patients received postoperative morphine via patient controlled analgesia (PCA); the dose was titrated up to 0.1 mg/kg IV according to the pain rating on a visual analog scale (VAS). Postoperative follow-up included noting the VAS and Ramsay sedation scores, morphine consumption, and seizure activity or other adverse effects at 0, 15, and 30 minutes and at 1, 2, 4, 6, 12, 24, and 48 hours.

• The sample was composed of 75 patients.
• Mean patient age was 47 years.
• Of all patients, 52% were female and 48% were male.
• All patients had meningioma, glioma, or brain metastases and were undergoing elective supratentorial craniotomy for tumor resection. All patients had tumors with a diameter no larger than 30 mm and a rating of greater than or equal to 15 on the Glasgow coma scale.
• Excluded from the sample were patients taking tricyclic antidepressants, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, or neuroleptic or antiepileptic drugs.

• Single site
• Inpatient
• Turkey

Randomized parallel-group trial

• Visual analog scale, to measure pain
• Ramsay sedation scale
• Glasgow coma scale

• During the first postoperative hour and at all time points, postoperative VAS scores were significantly higher (p < 0.0001) for those on phenytoin than for those on gabapentin.
• Compared to patients on gabapentin, patients on phenytoin consumed significantly more morphine (p = 0.01), totally and cumulatively.
• During the first two hours after surgery, patients on gabapentin had significantly higher sedation scores (p < 0.05) than did patients on phenytoin.
• Two patients were removed from the study prior to surgery because of apparent side effects of gabapentin. Side effects included severe fatigue and severe dizziness.
• Patients on gabapentin required less perioperative anesthesia than did patients on phenytoin.
• Individuals on gabapentin had a longer time to tracheal extubation (16.6 minutes, SD = 22 minutes) compared to those on phenytoin (4.5 minutes, SD = 2 minutes) (p < 0.001).

Use of gabapentin as a prophylactic anticonvulsant was associated with lower postoperative opioid consumption and lower pain severity. Gabapentin was associated with higher sedation in the immediate postoperative period and a longer time to extubation.

• The study had a small sample size, with fewer than 100 patients.
• The study had a risk of bias due to no blinding.
• The specified use of gabapentin was in a very specific patient population. Findings may not be applicable to other groups of patients.

Gabapentin had significant analgesic effects in patients who had undergone craniotomy, but pain relief was associated with increased sedation and longer time to extubation. In patients undergoing neurosurgery, determining causes of increased sedation or delayed extubation can be difficult and critical. Sedation and delayed extubation can contribute to difficulties in clinical care. Future research should investigate the timing and dosage of gabapentin, with the goal of taking advantage of the drug's positive effects while minimizing negative side effects.

To further validate previous findings that an axillary reverse mapping (ARM) technique enabling the preservation of arm lymphatics can reduce the postoperative lymphedema rate in women having sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND)

ARM was conducted intraoperatively with technetium in the breast and blue dye in the arm. Arm volume displacement measures were conducted preoperatively and every six months. Follow-up ranged from 3–54 months, with an average of 20 months. Lymphedema rates of sample cases were compared to those of a group that did not have ARM.

• N = 504   
• MEAN AGE = 57 years (SD = 13) 
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Of the participants, 90.6% had invasive cancer.

• SITE: Single site   
• SETTING TYPE: Inpatient

• PHASE OF CARE: Active antitumor treatment

• Single-arm, phase-II

• Arm water displacement

SNLB mapping was successful in 98.5% of the patients, and ALND lymphatics or blue nodes were identified in 71.8% of the procedures. After SLND, 0.8% had findings of lymphedema, and 6.5% had lymphedema after ALND. In cases where blue lymphatics were identified and able to be preserved, the SLNB lymphedema rate was 1.2%; the lymphedema rate in ALND cases was 6.9%. These rates were compared to reported rates with SLNB ranging from 0%–13%.

ARM may help preserve lymphatic structures and reduce the rates of postoperative lymphedema.

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Unintended interventions or applicable interventions not described that would influence results
• Measurement/methods not well described
• No other interventions for the prevention or treatment of lymphedema were reported.
• Actual measurements used for rate determination were not clear.

A variety of surgical techniques aimed at reducing postoperative lymphedema are being examined. This study describes one method of ARM that may be beneficial. Further research is needed to determine efficacy with concurrent comparison, the techniques that are most effective, and the role of ARM in overall lymphedema prevention and management.

To evaluate the impact of psychological intervention on pain perception and levels of alexithymia in patients with cancer

For six months, patients were randomly included in a psychological intervention or control group. The intervention consisted of biweekly 90-minute sessions provided by a clinical psychologist trained in psychotherapy and psycho-oncology. Main aspects included psychoeducation regarding mechanisms of pain, daily management of cancer-related issues, emotional reaction to illness, problem solving, cognitive restructuring of dysfunctional illness-related concerns and beliefs, stress management, and progressive relaxation. Investigators assessed outcomes at baseline and at the end of the study. Authors did not describe the control condition.

• The sample was composed of 104 patients.
• Mean patient age was 47.4 years.
• Of all patients, 55.8% were female and 44.2% were male.
• Subjects had a variety of cancer types. Gastrointestinal was the most frequent. Of all patients, 37.5% had metastatic disease. The average length of education was fewer than 10 years. Of all patients, 79.8% were married and 90% were receiving chemotherapy with or without radiation therapy.

• Single site
• Outpatient
• Italy

Randomized controlled trial

• Brief Pain Inventory
• Toronto Alexithymia Scale (TAS-20)
• Mental Adjustment to Cancer Scale
• Illness Behavior Questionnaire
• Hospital Anxiety and Depression Scale subscales for anxiety and depression
• SF-12

Control patients were significantly younger and had more progressive cancer than those in the intervention group (p = 0.01). In multiple regression analysis, only alexithymia and scores from the physical component of the SF-12 were predictive of pain intensity (p < 0.001). Patients with progressive disease had higher pain intensity, more interference with daily living, and worse pain (p < 0.001). At the end of six months, compared to controls, patients who received the intervention had significantly lower scores relating to pain intensity (p = 0.03), alexithymia (p < 0.001), hypochondriasis (p = 0.016), and disease perception (p = .013) and showed improvement in these problems from baseline (p < 0.007).

Findings of this study showed that the psychological intervention tested seemed to have a positive effect on pain and alexithymia in patients with cancer. Alexithymia was predictive of pain intensity.

• The study had risks of bias due to no appropriate control group, no attentional control, and no blinding. Authors did not describe the control condition.
• Authors did not discuss other interventions provided to manage pain, so whether differences and changes in medical management of pain influenced results is unknown.
• The control group had more progressive cancer and was younger. Both factors could have influenced pain and other outcomes.
• Authors did not state whether patients in the intervention group attended all sessions.
   

Findings suggest that psychological intervention, including cognitive behavioral techniques and progressive relaxation, can be helpful to patients in regard to management of pain; however, limitations of the study design must be considered when interpreting results. The intervention provided was time-consuming and would be associated with cost, which was not discussed. Future researchers should construct well-designed studies to determine the most helpful type and dosage of interventions of this type.

To evaluate the antiemetic efficacy of transdermal granisetron in chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately and highly emetogenic chemotherapy

• This article describes two clinical trials. The first, which was a phase II study, consisted of 210 patients with cancer. The second, which was a phase III study, consisted of 641 patients with cancer.
• Ages, gender, and key disease characteristics were not specified.

This was a multisite study conducted in the inpatient setting. The phase II trial was conducted in Germany. The phase III trial was conducted in nine countries.

All patients were in active treatment. Clinical applications of these studies are late effects and survivorship.

• The first clinical trial was a double-blind, double-dummy, randomized, multicenter study.
• The second trial was a randomized, active control, double-blind, double-dummy, parallel group, multicenter, multinational study.

In the first trial, patients used a Likert-type scale and visual analog scale (VAS) to measure CINV.

• No statistically significant differences were found in severity of nausea and vomiting, number of emetic episodes, or patient satisfaction between the two trial groups.
• Constipation was more common in patients treated with the granisetron patch compared with patients who were treated with oral granisetron.

Transdermal granisetron is effective and safe in controlling acute emesis induced by chemotherapy with moderate and high emetogenic potential; its efficacy and safety are fully comparable with those of oral granisetron.

Age, gender, cancer type, and stage were not mentioned.

The transdermal route may bring more comfort to patients. The patch is simple to apply and is maintained throughout chemotherapy without skin problems in most patients. The use of transdermal patch can avoid one of the many venous manipulations necessary in chemotherapy. Also, patches could be helpful in patients with swallowing problems.  Nurses need to consider obstacles, including cost and insurance coverage, when selecting antiemetics.

To determine the optimal dose of dexamethasone in combination with granisetron for chemotherapy-induced nausea and vomiting (CINV) control with cisplatin-containing chemotherapy

Patients were randomized to either receive 8 mg dexamethasone before chemotherapy and 24, 48, and 72 hours after chemotherapy during cycle 1, and 16 mg dexamethasone at the same time periods with cycle 2 of chemotherapy (8 mg antecedent group), or dosing of dexamethasone in the opposite sequence. All patients also received 3 mg granisetron with each dexamethasone administration. Physicians had discretion to provide addition treatment in cases of extreme nausea or vomiting. Symptoms were evaluated daily for 5 days.

• The study consisted of 36 participants.
• Age was not reported.
• The sample was 33% female and 77% male.
• All patients had head and neck cancers, with the most prevalent being hypopharyngeal.
• The majority of patients (83%) were chemotherapy naïve.

The study was conducted at a single site in Japan.

All patients were in active treatment.

This was a randomized crossover trial.

• The National Cancer Institute's (NCI) Common Terminology Criteria (CTC) version 2.0 for appetite loss was used.
• Nausea grade was defined in terms of number of vomiting episodes and ability to ingest liquids.
• Complete response was defined as no occurrence of nausea and zero instances of vomiting or retching.

Overall efficacy rates ranged from 47.2% on day 5 to 88.9% on day 1. No differences were found at any time point between groups.

No difference was found in antiemetic effect between 8 mg and 16 mg dexamethasone dosing.

• The sample size was small.
• The antiemetic regimen did not contain all recommended medications.
• Use of rescue medications was not discussed nor included in the definition of complete response.
• Whether the study team conducted nausea grading or it was based on patient reports was not clear.
• Nausea was defined in terms of vomiting rather than a symptom itself.

The study suggests that lower dosages of dexamethasone may be as effective as higher doses for CINV management. Further research in this area is needed. Lower dosing may help to reduce potential side effects of steroids.

To determine the effects of triple-drug therapy on chemotherapy-induced nausea and vomiting (CINV) in patients with head and neck cancer

Thirty men received 53 cycles of chemotherapy, and 11 women 18 cycles of chemotherapy consisting of cisplatin, docetaxel, and ​5-fluorouracil. Patients received concomitant radiation therapy except in the induction phase. Prior to each cycle, patients received fosaprepitant at 150 mg/kg, palonosetron at 0.75 mg/kg, and dexamethasone at 10 mg/kg. They also received dexamethasone at 6.6 mg/kg daily for three days after chemotherapy. Each patient received a diary to record their experiences of nausea and vomiting with each cycle.

• N = 41
• MEAN AGE = 59 years (range = 31–75 years)
• MALES: 73%, FEMALES: 27%
• KEY DISEASE CHARACTERISTICS: Head and neck cancers including laryngeal, oral cavity, nasopharyngeal, mesopharyngeal, and hypopharyngeal among others
• OTHER KEY SAMPLE CHARACTERISTICS: Patients received cisplatin-based regimens.

• SITE: Not stated
• SETTING TYPE: Not specified    
• LOCATION: Tokyo Medical University Hachioji Medical Center in Japan

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

Prospective, quantitative, nonrandomized, nonblinded trial

• A 0–100 mm Visual Analog Scale (VAS) was used to measure nausea (0 = no nausea, ≥ 0 and < 30 = slight nausea, ≥ 30 and < 70 = moderate nausea, ≥ 70 and < 100 = severe nausea, and 100 = very severe nausea).
• Patient diary with multiple choice questions
• Acute phase was day of administration
• The delayed phase was day of administration to day 5

A complete response (CR) was defined as no vomiting and no rescue therapy. In the overall phase, 69% (49 of 71) of courses achieved CR. The rate of no vomiting in the overall phase was 90.1%. Nausea in acute phase was reported as no nausea or slight nausea in 91.5% of patients. 87.3% of patients experienced no changes in or slightly reduced food intake, and 85.9% of patients reported good or relatively good general condition in the acute phase. In the delayed phase, no nausea to slight nausea was reported in 56.3% of patients, and 43.7% reported no changes in or slightly reduced food intake. 53.5% reported good to relatively good general condition.

In the overall phase, the majority of patients achieved a CR and reported no nausea or slight nausea. More patients experienced some nausea during the delayed phase than during the overall phase.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment) 
• Risk of bias (no appropriate attentional control condition)
• Measurement validity/reliability questionable 
• Findings not generalizable
• Questionable protocol fidelity
• Other limitations/explanation: The diary used to measure outcomes was not validated as a research tool. The findings were not generalizable because of the variation in cisplatin dosing, postoperative status of patients, and doses of radiotherapy.

Triple-drug therapy should be considered during prophylaxis for CINV in patients with head and neck cancer receiving chemotherapy. Although the majority of patients experienced CR during the overall phase, more patients experienced nausea in the delayed phase. Additional interventions to prevent and treat CINV in the delayed phase may be necessary.

To investigate whether L-glutamine (glutamine) decreases the severity of mucositis in the oral cavity, pharynx, and larynx induced by chemoradiotherapy (CRT)

Patients with squamous cell carcinoma of the nasopharynx, oropharynx, hypopharynx, or larynx (HNC) receiving CRT were randomized to orally receive either glutamine (group G) or placebo (group P) at a dose of 10 g three times per day throughout the CRT course.

• N = 40
• AGE RANGE = 38–77 years
• MALES: 34 (85%), FEMALES: 6 (15%)
• KEY DISEASE CHARACTERISTICS: Primary squamous cell carcinoma of the nasopharynx, oropharynx, hypopharynx, or larynx

• SITE: Single-site    
• SETTING TYPE: Inpatient  
• LOCATION: Osaka University Hospital, Japan

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

Double-blinded, randomized, placebo-controlled trial that excluded patients with active mouth or throat soreness before treatment, uncontrolled diabetes mellitus, or severe renal or hepatic insufficiency.

• Images of laryngoscope using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3
• Hematologic and blood chemistry tests were performed at baseline, once per week during the study treatment (weeks one to six), and after treatment (weeks seven to nine) or until patient discharge, whichever occurred first.
• Pain score according to a numerical rating scale (NRS) 
• The primary treatment outcome was evaluated 10 weeks after the completion of treatment using computed tomography (CT), positron emission tomography-CT (PET-CT), and biopsy.

The study demonstrated that glutamine significantly decreased the severity of CRT-induced mucositis in patients with HNC. Patients (group G) receiving glutamine had a decreased the incidence of grade 4 mucositis. The mean duration of supplemental nutrition because of severe mucositis was significantly shorter in group G than in group P (group G, 18 ± 13; group P, 27 ± 11; p = .046). Treatment delay caused by mucositis was observed in zero patients in group G and in 15% of patients in group P. In addition, NRS scores were significantly lower in group G than in group P at weeks 4, 5, and 6 (p = .049, p = .019, p = .032, respectively).

The study showed that glutamine significantly decreases the severity of CRT-induced mucositis in patients with cancer, which in turn will improve quality of life for patients.

• Small sample (< 100)

This study could not provide conclusive results of glutamine in the prevention and treatment of oral mucositis. The study indicated the need for an integrative and multidisciplinary approach in patient care, which could result in substantial advances in the outcomes of cancer therapy and the improvement in patient quality of life. However, there is no known specific dose for glutamine, and it has not been approved by the U.S. Food and Drug Administration for the treatment of mucositis during chemoradiotherapy.

To determine the optimal IV granisetron dose, 1 or 3 mg, in patients with cancer receiving moderately emetogenic chemotherapy (MEC) or high emetogenic chemothrerapy (HEC)

Patients received 1 mg or 3 mg granisetron with adequate dosing of dexamethasone (20 mg IV dexamethasone on day 1 for patients receiving cisplatin-, anthracycline-, and cyclophosphamide-based regimens and 10 mg IV dexamethasone prior to chemotherapy for patients receiving MEC regimens). Granisetron and dexamethasone were diluted and administered 10-30 minutes before chemotherapy. Rescue antiemetic medication was possible, and the usage was recorded. Nausea and vomiting were recorded for seven days.

• This study reported on 359 patients.
• The age range of patients randomized to 1 mg granisetron group was 26–89 years old. The age range of patients randomized to 3 mg group was 22–84 years old.
• MALES (%)  overall 162 (45%); 3 mg cohort: n=25%; 1 mg cohort: n=21%   FEMALES (%) overall 197 (55%);  3 mg cohort: n=26%; 1 mg cohort: n=29%
• Cancer diagnoses were gastrointestinal, breast, lung, and other malignancies.

This was a multisite study conducted at 10 centers located throughout Japan. The setting type was not specified.

Patients were undergoing the active treatment phase of care.

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

Patient diaries were used to record episodes of acute and delayed nausea, vomiting, use of rescue antiemetics, and bowel patterns.

Results indicated that 1 mg of granisetron was not inferior in effect to a 3-mg dose. The primary endpoint was the proportion of patients with a complete response during the first 24 hours after chemotherapy. For the primary endpoint, 359 patients were evaluable according to the modified intention-to-treat (ITT) analysis. Complete protection was achieved in the modified ITT population, 90.6% and 88.8% for the 3- and 1-mg groups, respectively (p < 0.0001); however, results met the stated margin to demonstrate noninferiority. The secondary efficacy analysis showed that the maximum grade of nausea in the acute phase was similar in both groups (p = 0.61). In addition, no significant difference was found between the two groups in the number of vomiting episodes (p = 0.62). No statistically significant differences were observed in the maximum grade of nausea in the delayed phase (from day 2 to 7; p = 0.67). Adverse events on day 1 as well as on days 2–7 after chemotherapy were mild and not significantly different in both groups. No severe or unexpected adverse events were reported.

This study showed that 1 mg granisetron is not inferior to 3 mg when both doses are combined with dexamethasone, assuming that a 15% difference in complete response rate is accepted.

• The authors reported a limitation because of a wide delta margin (15%), however, a 95% confidence interval (CI) existed.
• Variation in chemotherapy regimens and diagnosis existed; these were not stratified to the two cohorts. Gender should have been stratified to the two cohorts as it is known that females experience nausea more often than males. Patients should also have been stratified according to the severity of their previous experience of CINV.

Findings suggest that lower dose granisetron may be effective for control of acute and delayed CINV.