Examine the efficacy of purported chemoprotective agents to prevent or limit neurotoxicity of cisplatin and related agents

TYPE OF STUDY: Combined systematic review and meta-analysis

DATABASES USED: Cochrane Neuromuscular Disease Group Specialized Register, Cochrane Central Register of Controlled Clinical Trials, MEDLINE, EMBASE, LILACS, and CINAHL

KEYWORDS: Extensive list provided in article appendix

INCLUSION CRITERIA: Quasi-randomized or randomized clinical trials whose participants received cisplatin (or related compounds) chemotherapy with or without a potential chemoprotectant and were evaluated zero to six months after completing chemotherapy using quantitative sensory testing (primary) or other measures, including nerve conduction studies or neurologic impairment rating using validated scales (secondary)

TOTAL REFERENCES RETRIEVED: Sixteen randomized trials were evaluated in the initial 2006 review. In the 2010 update, 11 additional randomized trials not among the 2006 review were identified.

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Cochrane method of evaluation for risk of bias done by two authors and finalized by consensus

• N (studies) = 6
• SAMPLE RANGE ACROSS STUDIES: 14–242
• TOTAL PATIENTS INCLUDED IN REVIEW: 1,537 participants
• KEY SAMPLE CHARACTERISTICS: Patients who received cisplatin chemotherapy

Cisplatin is considered to have neurotoxic effects, with patients developing sensory neuropathy. Symptoms of pain, numbness, and tingling are observed mostly in the extremities from a distal to proximal distribution. The neuropathy experienced by patients may recover partially or may become permanent. Neuroprotective agents such as acetylcysteine, acetyl-L carnitine, amifostine, calcium and magnesium, growth factors, glutathione, ORG 2766, oxcarbazepine, and vitamin E have been tested. The five newly added randomized controlled trials included three chemoprotective agents not previously described in the 2006 review.

From the data examined in this updated review, inconclusive evidence exists for recommending any neuroprotective agent tested to prevent or limit the neurotoxicity of platinum chemotherapy.

While 1,537 participants were included in the 2010 update, few trials were amenable to meta-analysis. Clinical trials of neuroprotective agents are plagued by issues of study design, including small sample size, unclear randomization and blinding procedures, and lack of quantitative measures, especially conventional QST or electrophysiologic evaluation.

To determine the efficacy of sucralfate mouthwash in the prevention of oral mucositis (OM) in patients receiving fluorouracil (5-FU) chemotherapy

Patients 18 years and older receiving chemotherapy containing 5-FU and calcium folinate were randomized into two groups through a computer-generated list of random numbers. One group received sucralfate suspension mouthwash and the other group received a placebo. Both groups received 10 ml of either sucralfate or placebo mouthwash every six hours for 10 days after the last dose of chemotherapy. Patients were instructed to rinse their mouth with the suspension for at least five minutes and spit it out 30 minutes after meals to ensure prolonged exposure of the mouthwash to the mucosal membranes.

• N = 51   
• AGE = Older than 18 years
• MALES: 15 (sucrafate group), 20 (placebo group); FEMALES: 10 (sucralfate group), 6 (placebo group)
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Gastrointestinal cancer (e.g., esophageal, colon, rectal, gastric)

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: Imam Khomeini Educational Hospital, Sari, Iran

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

• Double-blind, randomized controlled study

• World Health Organization (WHO) grading system for mucositis
• Visual analog scale (VAS) to grade pain intensity

A statistically significant difference in the severity of mucositis was shown between the sucrafate group and placebo group on both day 5 and day 10 (p = 0.005, p < 0.001), respectively. The severity of mucositis in the sucrafate group on day 5 and 10 was grade 0. The majority of patients in the placebo group had a mucositis severity grade 2 on day 5 and day 10. A statistically significant reduction in pain intensity was shown in the sucrafate group versus the placebo group on both day 5 and day 10 (p = 0.004, p = 0.001), respectively.

Sucralfate mouthwash may be more effective than placebo in the prophylaxis of 5-FU–induced OM. A correlation between both the reduction of pain intensity and mucositis severity was shown with the use of the sucralfate mouthwash suspension, further confirming the role of sucralfate in the prophylaxis of OM in patients receiving 5-FU chemotherapy.

• Small sample (< 100)

Sucralfate mouthwash may be effective in reducing the severity and pain intensity of OM in patients receiving 5-FU.

The objective of this study was to compare the effectiveness of bleomycin as a sclerosing agent with povidone-iodine with respect to efficacy, cost, accessibility, safety, ease of administration, and number of doses for complete response.        

Forty participants were assigned into two treatment groups of bleomycin treatment or povidone-iodine treatment via block randomization. A 28Fr. chest tube was placed in all patients at the bedside under local anesthesia with opioids given for pain. The following day, both groups had a sclerosing agent instilled in the chest tube for one hour; bleomycin at 1 mg/kg in 60 mL saline in the study group and povidone-iodine 10%, which was diluted to obtain a final concentration of 2.5% povidone-iodine in the control group. Both groups had 5 mL of 2% lidocaine solution added to the sclerosing agent. In both groups, the chest tubes were clamped for one hour and then connected to water seal. All patients were admitted to the same unit in the hospital and experienced the same post-pleurodesis respiratory and pain management protocols. The chest tube remained in place until output decreased to 200 mL; if high output persisted more than 10 days, a Heimlich valve was placed and patients were discharged from the hospital. Chest x-rays were obtained post-chest tube removal and at 30 days post-procedure to evaluate size of pleural effusions. Pain and dyspnea after drainage ratings were recorded at discharge and at 30 days post-op. 

The sample was comprised of 39 patients.

Key disease characteristics included

• Biopsy- or cytology-proven malignant pleural effusions with a variety of types of cancer
• Effusions previously treated with and showing improvement with thoracenteses but recurrent or symptomatic when entered in study.

Key sample characteristics included

• Symptomatic benefit from thoracenteses
• Chest radiograph confirming lung expansion of 90% or more after therapeutic thoracenteses
• Karnofsky performance status index greater than or equal to 70
• No one with comorbidities that would exclude them from general anesthesia
• No bleeding disorders, massive skin infiltration, or active infectious disease.
   

This single-site study was conducted in the inpatient unit at Valiasr Hospital in Tehran, Iran.

• Patients were undergoing long-term follow-up care.
• The study has clinical applicability for end-of-life and palliative care.
   

The study was a randomized clinical trial.

• Chest tube placement, +/- Heimlich valve    
• Numeric pain scale
• Chest x-ray
• Dyspnea scale (1–10)
   

• According to author reports, the groups were equivalent in demographic variables, but this data was not visible to the reviewer.
• No significant difference was seen between groups with respect to age, duration of thoracostomy, volume of pleural effusion, dyspnea score after drainage, fever, and pleural effusion after drainage, discharge, and one month later.
• Patients in the bleomycin group had significantly lower dyspnea scores at the one-month follow-up time compared to the povidone-iodine group.
• Complete pleurodesis occurred in 79% of the bleomycin group and 75% of the povidone-iodine group, which is not a significant difference in treatment results.

• Bleomycin is more effective at long-term dyspnea management based on one-month follow-up reports.
• No differences were observed between groups based on pain score following procedure, dyspnea at discharge, or reoccurrence of pleural effusion at the one-month follow-up visit. 
• Neither method demonstrated extremely superior results and appear similar in overall effects.

• The study had a small sample size of less than 100 patients.
• Groups were not matched by age and sex.
   

When compared with povidone-iodine, bleomycin offers the advantage of being more effective for dyspnea symptoms one month post-procedure. However, both methods appear similar in terms of pain scores, dyspnea at discharge, and recurrence of pleural effusions at one-month follow-up. For patients with concerns of iodine absorption or side effects, bleomycin would be a comparable sclerosing agent.

To determine if brief guided imagery or music can reduce patient pain and anxiety during cutaneous procedures

Consecutive adults undergoing surgery for basal or squamous cell carcinoma of the face were randomized to three groups: (a) guided imagery, (b) music, or (c) control. The guided imagery patients were sent a recording of the guided imagery by mail and instructed to listen to this at least once daily starting at least four days before surgery. Those in the music group listened to music via earphones during the surgery. Patients in the other two groups also wore earphones during the surgery, but without any sound. Pain and anxiety scores were obtained before and after the procedure on the day of surgery.

• N = 155   
• MEDIAN AGE = 62.4–64.2 across study groups 
• MALES: 58%, FEMALES: 42%
• CURRENT TREATMENT: Other
• KEY DISEASE CHARACTERISTICS: All had basal or squamous cell skin cancer and were undergoing facial surgery
• OTHER KEY SAMPLE CHARACTERISTICS: No significant differences across groups in the duration of surgery

• SITE: Single site   
• SETTING TYPE: Not specified    
• LOCATION: Northwestern University Hospital

• PHASE OF CARE: Active antitumor treatment

• Single-blind randomized, controlled trial

• Visual analog scale (VAS) for pain
• State-Trait Anxiety Inventory (STAI) short form
• Heart rate
• Blood pressure

There were no significant differences in average change in pain or anxiety scores between groups.

The visual imagery and music interventions as used here had no apparent effect on perioperative pain or anxiety.

• Unintended interventions or applicable interventions were not described that would influence results.
• Measurement validity/reliability questionable
• The logic of expecting to see a decline in pain from pre-op to post-op is questionable.
• No patient education on the use of the visual imagery recording was given.
• Patient adherence to use of the visual imagery was not explored.

This study did not show an effect of music or visual imagery on perioperative pain or anxiety. The lack of effects may be associated with the ways in which the interventions were provided or in the study design—it would be expected that pain should increase postoperatively and anxiety would decline after the surgery was completed. In addition, analysis was done regarding pre- and post-symptom change rather than actual postoperative symptom levels.

To determine the feasibility of an exercise intervention among women receiving treatment for breast cancer and to examine the effects of exercise on hemoglobin (Hb) and maximum oxygen volume (VO2MAX) and their association with changes in cancer-related fatigue (CRF) and quality of life (QOL) while investigating changes in selected inflammatory markers

The intervention consisted of a supervised, progressive treadmill exercise program two to three times times per week delivered in a rehabilitation center for the duration of chemotherapy (9–12 weeks).

• N = 14  
• AGE = Aged 21 years and greater
• FEMALE: 100%
• KEY DISEASE CHARACTERISTICS: Stages I–II breast cancer
• OTHER KEY SAMPLE CHARACTERISTICS: No history of depression, arthritis, or joint pain in the prior three months; engaged in regular exercise for five days per week in past three months; other uncontrolled conditions 

• SITE: Multi-site    
• SETTING TYPE: Outpatient    
• LOCATION: Southern California and Virginia

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

Random assignment with repeated measures

• Feasibility: Measured by recruitment, retention, adherence to exercise protocol, tolerance of exercise testing, and the completion of data collection
• Efficacy: Measured by Hb concentration (venous blood), VO2MAX (using the Trackmaster TM500/S^® by JAS Fitness Systems in Carrollton, TX), CRF (Piper Fatigue Scale [PFS]), QOL (Functional Assessment of Cancer Treatment - Breast [FACT-Breast]), and inflammatory markers (IL6, IL10, cortisol, and myeloperoxidase) using laboratory kits

Feasibility: The recruitment rate was 45.7%, the retention rate was 87.5%, the adherence rate was 95%–97%, and the tolerance rate was 93%.  

Efficacy: There were no differences in VO2MAX at baseline between the groups. The exercise group maintained pretreatment VO2MAX levels throughout chemotherapy, and the usual-care group showed a significant decline of as much as 6.3 ml/kg per minute that continued three to four weeks after treatment. CRF outcomes favored the exercise group, and QOL, physical well-being, and functional well-being declined significantly in both the experimental and usual-care groups.

Recruitment to exercise interventions is difficult. The type of exercise, location, and the choice of a self-lead or a supervised intervention may influence the decision to participate. Retention may be influenced by flexibility in scheduling and the allowance of make-up sessions. Exercise did not have a significant effect on CRF or QOL. Changes in the inflammatory markers favored the exercise group. Exercise may protect against a decline in VO2MAX but not Hb concentrations.

• Small sample (< 30)
• Risk of bias (no blinding)
• Risk of bias(sample characteristics)
• Unintended interventions or applicable interventions not described that would influence results 
• Findings not generalizable
• Intervention expensive, impractical, or training needs

This study addressed exercise dose in terms of intensity, duration, and frequency when prescribing exercise as an intervention. The inclusion of inflammatory markers is a potential benefit that future research could use to quantify the effects of an exercise intervention.

To evaluate the effects of honey on severe oral mucositis

Patients were randomized to the honey or control group. The experimental group was given a topical application of honey before the development of mucositis. Both groups received routine oral hygiene with lidocaine, mycostatin, daktarin mouth gel, and mouthwash.

• N = 40   
• MEAN AGE = 8 years (SD = 4.2 years)
• MALES: 52.5%, FEMALES: 47.5%
• CURRENT TREATMENT: Combination radiation and chemotherapy
• KEY DISEASE CHARACTERISTICS: Hematologic tumors were most common.

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: Saudi Arabia

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

Open-label, randomized, controlled trial

• World Health Organization (WHO) mucositis grading
• Oral cultures

Analysis showed an absolute risk reduction for the development of grade 3–4 mucositis of 35% among those using honey (p = 0.02). Less Candida colonization (p = 0.003) and bacterial colonization (p = 0.003) were seen in the honey group.

Honey may have some benefit in the management of oral mucositis.

• Small sample (< 100)
• Risk of bias (no blinding)
• Unintended interventions or applicable interventions not described that would influence results
• Frequency of use of honey not clearly described
• Frequency of oral care not clearly described

There may be some benefit from the use of honey to coat oral mucosa in the management of chemotherapy-induced oral mucositis. This study had several limitations.

To determine if the use of a hologram bracelet is effective in the management of chemotherapy-induced nausea and vomiting (CINV) in adult patients with cancer

A hologram bracelet was used as the intervention, and a counterfeit bracelet was used as the placebo. The control group did not use any bracelet. All groups received standard antiemetics. Data were collected through three cycles of chemotherapy for each participant using daily diaries and the Functional Living Index-Emesis (FLIE) questionnaire. The hologram bracelet is said to stabilize body energy by covering very low intensity magnetic fields. Theoretically, it attracts special charges that affect the brain in terms of regulating neurotransmitters that play a role in causing nausea and vomiting. Another theory is that the hologram reflects infrared rays into the body, which stimulate secretion of these same neurotransmitters. Data were collected at baseline, on the first day of chemotherapy, and then daily on days 2–5 for three cycles. Patients were randomized to one of three groups: hologram, placebo, and usual care control.

• N = 175   
• AGE = 18–75 years
• MEAN AGE = 42.3 years
• MALES: 31.4%, FEMALES: 68.6%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Any type and stage of cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Inpatient and outpatient adults who received at least one cycle of chemotherapy and experienced nausea and vomiting, various levels of emetogenicity of treatment with 58.5% on HEC regimens

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

PHASE OF CARE: Active antitumor treatment

• Randomized, double-blinded, placebo-controlled trial

• Participants’ medical records
• FLIE questionnaire
• Daily diary

Less anticipatory chemotherapy-induced vomiting (CIV) severity existed in the hologram group in cycles 2 and 3 (p < 0.5). The hologram group experienced less anticipatory chemotherapy-induced nausea (CIN) only during the cycle 3 (p < 0.03). In the acute phase, no difference in CIV existed between the three groups but less CIN in the intervention group at all three cycles (all p's < 0.05). In the delayed CIV phase, the severity and frequency of CINV was significantly lower in the hologram group. Men experienced a greater positive effect than women. Overall, the hologram group had positive effects on both nausea and vomiting but greater effects on nausea. A decrease in antiemetic use was also noted. In evaluating the FLIE, higher mean scores were found in the hologram group during all three cycles of chemotherapy (p < 0.05).

The use of the hologram bracelet worn at all times during three cycles of emetogenic chemotherapy showed a significant decrease in CINV, higher levels of activities of daily living, and decreased use of antiemetics. Antiemetic prophylaxis regimens are not clearly described.

• Unintended interventions or applicable interventions not described that would influence results
• Changes in chemotherapy and antiemetic regimens during the three cycles
• Influence of the placebo effect and self-reporting biases
• Varied emetogenic levels of chemotherapy with no relevant subgroup analysis
• Antiemetic medications used are not clearly reported or standardized
• The use of rescue medication is not addressed.

The use of a hologram bracelet may be effective as a complement to standard antiemetic use in reducing CINV but especially in increasing quality of life during treatment. This may have an effect particularly on nausea symptoms.

To investigate the effectiveness of psychotherapy for treating depression in incurable cancer patients and to evaluate the effectiveness of psychotherapy on anxiety, general psychological distress, control of cancer symptoms, quality of life, and coping measures

Databases used, in September 2005, were Cochrane Pain, Palliative and Supportive Care Group Register, Cochrane Controlled Trials Register, MEDLINE, EMBASE, CINAHL, and PsycINFO. Investigators looked for additional studies in the  SciSearch database and contacted the authors of significant studies to identify trials for inclusion. Search keywords were psychotherapy, aromatherapy, art therapy, autogenic training, behavior adjustment therapy, biofeedback, implosive therapy, relaxation, yoga, hypnotherapy, imagery and psychotherapy, counseling, group therapy, socio-environmental therapy, depression, depressed, depressive, neoplasm, tumor, cancer, and carcinoma or malignancy. Authors provide extensive detailed lists of the search strategies and terms used with each database.

To be included in the analysis, studies had to 

• Involve psychotherapy of any kind, including interventions such as music therapy
• Include at least one validated measure of the severity of depression, either by self-report or rating by an observer
• Include only participants 18 years old or older who had a primary diagnosis of incurable cancer
• Be randomized controlled trials

Excluded from the analysis were interventions that were not considered forms of psychotherapy, such as aromatherapy and therapeutic touch.

The initial search identified 176 studies for possible inclusion. Of these, two independent raters identified 16 studies as potentially suitable. Six of these were eliminated because they involved interventions such as aromatherapy or structured nursing assessment. The final set of literature included 10 studies. None met risk-of-bias criteria for “good” study quality.

• The final sample of 10 studies included a total of 780 participants. Sample size per study was 20–235.
• Subjects for meta-analysis were obtained from three main groups: patients with metastatic breast cancer (five studies), patients receiving palliative care (three studies), and various patients with advanced cancer (two studies).

Of the 10 studies analyzed

• Five studies used, for the most part, supportive psychotherapy
• Three studies investigated, mosly, behavioral therapies, including relaxation techniques
• Some used cognitive behavioral and problem-solving therapies
• One study involved group therapy sessions

The duration of interventions, across studies, was 3–5 sessions.

Six studies had data that could be used in the meta-analysis of the effects of psychotherapy on depression. All used the Profile of Mood States (POMS) scale. Four involved supportive psychotherapy, one involved cognitive behavioral therapy, and one used problem-solving therapy.

• Combined data involved 292 participants in the psychotherapy arm and 225 in the control arm.
• Combined data showed that psychotherapy had a significant effect on depression among participants (SMD = –0.44, 95% CI –0.08 through –0.80).
• Statistically significant heterogeneity was observed among the six studies (p = 0.004).

Five studies could be used in the meta-analysis of the effect of psychotherapy on anxiety and general psychological distress. The five studies included 242 participants in the psychology arm and 169 in the control.

• Psychotherapy had a borderline effect on anxiety (SMD = –0.68, 95% CI 0.01 through –1.37).
• Statistically significant heterogeneity was observed (p < 0.00001).
• Four studies provided data on general psychological distress by using the POMS total mood disturbance score. Analysis included 237 participants in the psychotherapy arm and 166 in the control.
• Psychotherapy had a significant effect on distress (SMD = –.94, 95% CI = –0.01 through –1.87).
• Heterogeneity was statistically significant (p < 0.00001).

Other findings follow.

• Too few studies provided data to evaluate symptom control, quality of life, coping measures, or severity of physical symptoms.
• Subgroup analysis was done using studies of patients with metastatic breast cancer. Findings were similar and significant for depression, anxiety, and general distress.

Findings suggest that the depression that patients with advanced cancer experience can be effectively ameliorated by psychotherapeutic intervention. However, questions remain concerning duration of effectiveness and timing of interventions. Most studies included in the meta-analysis investigated the impact just after or during continuous cancer treatment and included a limited number of sessions. Effectiveness is further in question because studies did not show that patients were clinically depressed or suffered from depressive disorders. Authors noted that the effects of psychotherapy, as revealed in the meta-analysis, were almost comparable to those observed with antidepressant pharmacotherapy.

Although the analysis discovered significant findings regarding the use of psychotherapeutic interventions for depression, anxiety, and psychological distress, the quality of individual studies was not high and studies involved significant heterogeneity. Subjects’ physical status was not clearly defined. Some studies involved patients during active treatment, so it is unclear if findings are applicable to patients with end-stage disease. The cost associated with psychotherapeutic interventions requiring trained mental health professionals could not be evaluated. Providing such  interventions for many patients may be impossible, from the financial standpoint. Not enough studies met the criteria for meta-analysis to allow the authors to determine the impact of demographic and cultural differences on findings. These differences may influence involvement in and response to psychotherapy. Similarly, differences between types of therapy employed could not be evaluated.

Future research in this area should clarify the cost-effectiveness of psychotherapy. This area could benefit from research studies of higher quality, which would clarify effectiveness. Investigators noted that experts often recommend specific types of therapy, particularly cognitive behavioral therapy. However, this systematic review points to the need for more well-designed clinical trials to clarify the actual effect of each therapy on depression as well as on other patient outcomes.

Patients kept ice chips and ice-cold water in their mouths for 15 minutes before and during as well as for an additional 90 minutes after melphalan infusion. Patients were advised to continue swirling ice chips around in their mouths and to gargle and swallow ice-cold water every 10–20 minutes throughout oral cryotherapy. Patients were consecutively compared with a historical control group (no cryotherapy). Fludarabine was administered at 25 mg/m² daily for five days; melphalan was administered at 70 mg/m² daily for 15 minutes for two days.

The sample consisted of 18 patients undergoing allogeneic hematopoietic stem cell transplant (HSCT) receiving fludarabine and high-dose melphalan (140 mg/m²).

Common toxicity criteria (CTC) grading of stomatitis (0–4) was done every day from the first day of HSCT to day 28. The maximum grade recorded for each participant was considered that patient's grade.

• The cryotherapy group reported less moderate to severe mucositis with 2 out of 18 patients (11.1%) in the cryotherapy experiencing moderate to severe mucositis (grade 2 or 3) and 6 out of 7 patients (85.7%) in the historical control group experiencing grade 2 or 3 mucositis (p = 0.001).
• No patients in the cryotherapy or control group developed grade 4 mucositis.
• Side effects included chills (n = 7; 39%) and nausea (n = 4; 22%), and one patient discontinued cryotherapy.

The sample size was small sample, and the control group was based on historical reports.

To evaluate the effect of an increased duration of aprepitant for the prevention of chemotherapy-induced nausea and vomiting (CINV)

Women scheduled to receive AC regimens (doxorubicin and cyclophosphamide) enrolled in the study were randomly assigned to two groups. One group received a three-day aprepitant regimen in the first course of chemotherapy and six days in the second course. The other group received six days of aprepitant in the first course and three days in the second course of chemotherapy. All patients also received 8 mg dexamethasone IV on day 1 followed by 80 mg dexamethasone daily. During the six day course, dexamethasone was given for six days, and on the three-day regimen, it was given for three days. A 30-day washout existed between courses. Study measures were done at baseline for both chemotherapy cycles and seven days later.

• N = 49
• MEAN AGE = 38.7 years (SD = 6.5)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All had breast cancer.
• OTHER KEY SAMPLE CHARACTERISTICS: No indication of patients being chemotherapy naive

• SITE: Single site  
• SETTING TYPE: Outpatient  
• LOCATION: Iran

• PHASE OF CARE: Active antitumor treatment

• Randomized, controlled, crossover trial

• Eastern Cooperative Oncology Group (ECOG) toxicity questionnaire 
• Complete response (CR) defined as no nausea and no episodes of vomiting

Sixty-three percent had CR with the six-day regimen compared to 39% with the three-day regimen (p < 0.001). The order of treatment regimens did not affect results.

The use of aprepitant and dexamethasone for six days was more effective than a three-day regimen for the prevention of CINV.

• Small sample (< 100)
• Risk of bias (no blinding)
• Measurement validity/reliability questionable
• The ECOG questions for nausea have questionable validity for symptom measurement.
• No 5-HT₃ was administered, which is recommended for AC regimens.

Findings suggest that the provision of an antiemetic regimen for a longer duration in patients receiving highly emetogenic chemotherapy may be more beneficial to prevent CINV than current three-day regimens. Further well designed research in this area would be helpful.