To evaluate the safety and efficacy of the addition of aprepitant in patients receiving carboplatin-based chemotherapy after initial doublet-based antiemetics in the first chemotherapy cycle

In the first cycle of chemotherapy, patients were receiving doublet therapy, consisting of a 5-HT₃ and dexamethasone. In the second cycle, patients received aprepitant and reduced dexamethasone, as in standard triplet regimens. Patients completed daily questionnaires regarding vomiting frequency, nausea scoring, and food intake for five days of each cycle.

• N = 63   
• MEAN AGE = 66 years
• AGE RANGE = 44–81 years
• MALES: 79.4%, FEMALES: 20.6%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Tumor types were not stated, but 11.1% had brain metastases and 71.4% had a stage IV disease.

• SITE: Single site   
• SETTING TYPE: Not specified    
• LOCATION: Japan

• PHASE OF CARE: Active antitumor treatment

• Observational

• Evaluation of complete response (CR) rates (no vomiting and no rescue antiemetics)
• Common Terminology Criteria for Adverse Events (CTCAE), version 3.0

The overall (p < 0.001) and delayed phase (p < 0.001) CR rates were better in the second cycle with the addition of aprepitant. No difference existed in the CR rates in the acute phase. Fewer patients in the second cycle required rescue antiemetics (p = 0.006). The proportion of patients who had grade 2 or higher nausea was less in the cycle with aprepitant (p = 0.013).

The addition of aprepitant significantly improved CINV control.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Experience of CINV in the first cycle could have influenced experiences in cycle 2 and beyond.

This study showed that the addition of an NK₁ as salvage for patients on MEC who did not have complete control in initial chemotherapy cycles was associated with improved CINV control, particularly in the delayed phase.

To explore the extent to which peritoneal dialysis (PD) patients are affected by constipation, how many laxatives they use on a regular basis, and barriers to managing constipation when their dietary fiber is increased.

In stage 1, the investigators established current bowel habits and laxative use. In stage 2 (N = 23), fiber intake was increased by 6 to 12 g per day using a dietary fiber supplement, partially hydrolyzed guar gum (PHGG). Finally, in stage 3 (N = 17), patients' daily diet was modified to include foods naturally high in fiber, aiming for 6 to 12 g per day more than their current intake, and bowel habits and laxative use were monitored.

A stool-and-laxative recording diary was sent to 126 PD patients. Forty-six reported using laxatives. All respondents using laxatives were invited to use a soluble dietary fiber supplement for four weeks, followed by dietary advice to see whether they could achieve the same effect using high-fiber foods.

• The study reported on a sample of 23 PD patients using laxatives.
• Patients were included in the study if they had received PD at home for at least three months.

United Kingdom

This was a descriptive study with a three-stage audit and intervention project.

A stool-and-laxative diary was used to measure number of bowel movements per day.

• In stage 1, a recording diary was sent to 126 patients with PD. Seventy patients returned the diary, and 46 reported using laxatives.
• In stage 2, 23 of 46 patients entered the intervention stage. Seventeen succeeded in replacing prescribed laxatives with the fiber supplement. All 23 patients successfully increased fiber and reduced laxative use within a four-week period.
• In stage 3, 17 patients were asked to increase dietary fiber by modifying their daily food intake. Sixteen tried to increase their intake of high-fiber foods; of them, 8 succeeded. However, only two patients were able to reduce their fiber supplement intake.

Fiber supplementation may be as effective as laxative treatment in preventing constipation. In addition, fiber supplementation was preferred by patients in this study, as many felt it improved bowel habits without the side effects of stimulant laxatives.

Fiber supplements cost much more than standard laxatives.

• The sample size was small.
• Only eight patients tried to increase their dietary fiber intake, limiting the value of the study. 
• The fiber supplement was used as a thickening and stabilizing agent. It helped renal patients on fluid restriction because psyllium and methyl cellulose require a lot of fluids to be effective. In addition, PHGG has negligible potassium and phosphate. This is not transferable to patients with cancer unless they are in renal compromise.
• The research design had flaws.
• The study did not compare the use of bulk-forming fiber or dietary with soluble fiber.
• A subjective patient-preferred questionnaire was administered. No tool was presented for patient outcomes assessed, which can be subjective for the clinicians evaluating the study.

Eight hundred mg vitamin E was diluted with corn oil (volume = 2 mL). Patients swished for at least 30 seconds then spat it out. The control group received corn oil only. Subjects did not rinse mouths for 30 minutes after spitting out the solution. Forty-five cycles of the study drug were administered (one cycle: four patients, two cycles: five patients, three cycles: one patient, four cycles: four patients, six cycles: five patients; vitamin E = 22 cycles, placebo = 23 cycles).

• N = 16
• AGE: Pediatric patients aged 6–18 years
• KEY SAMPLE CHARACTERISTICS: Planned chemotherapy for two identical cycles of doxorubicin-containing chemotherapy with doxorubicin at least 60 mg/m². Patients had chemotherapy regimens with one to three treatment sets consisting of two to six doxorubicin-containing chemotherapy cycles.

• Randomized, controlled, double-blind N-of-1 Bayesian analysis study

• Oral Mucositis Assessment Scale (OMAS) days 7, 10, 14, and 17 of each cycle
• Visual analog scale (VAS) score for pain and difficulty swallowing
• World Health Organization (WHO) scale in diary by participant or parent
• Amount of opioid analgesia
• Topical oral analgesia
• IV hydration
• Total parenteral nutrition
• Episodes of febrile neutropenia
   

Compliance was 84% with no statistically significant findings. Vitamin E was not associated with reduction in pain VAS scores or swallowing difficulty. WHO mucositis scores were similar for vitamin E and placebo cycles. No differences for the additional secondary outcomes between vitamin E and placebo cycles were found. Authors noted that vitamin E should not be used in this context. N-of-1 study design was found to be a potentially effective design method.
 

• Small study
• Data collection issues
• No significant findings
• The order in which the placebo and vitamin E cycles were administered is unclear.
   

PHASE OF CARE: Active antitumor treatment

Cryotherapy or low-level laser therapy may be offered to cooperative children receiving chemotherapy or HSCT conditioning with regimens associated with a high rate of mucositis. Keratinocyte growth factor (KGF) may be offered to children receiving HSCT conditioning with regimens associated with a high rate of severe mucositis. However, KGF use merits caution as there was a lack of efficacy and significant toxicity data as well as a lack of long-term follow-up data in pediatric cancers. No other interventions were recommended for oral mucositis prevention in children.

• Cryotherapy: Weak recommendation with moderate to quality evidence
• Low-level laser therapy: Weak recommendation with high-quality evidence
• KGF: Weak recommendation with high-quality evidence

No keywords, inclusion criteria, or exclusion criteria were stated in the article.

Although some information was missing in this study, the decision making process and results of the evidence review were well-described. The inclusion of a description of research gaps, summarized in a table, showed the comprehensiveness of this review.

To evaluate prophylactic colony-stimulating factors (CSFs) given concurrently with or after initiation of chemotherapy prior to the development of neutropenia compared with placebo or no therapy in patients with cancer undergoing chemotherapy or hematopoietic stem cell transplantation (HSCT)

The standard Quality of Reporting of Meta-Analyses (QUOROM) guidelines were used to guide the search.

DATABASES USED: Electronic searches of Ovid MEDLINE from 1966–April 24, 2007; EMBASE from 1980–April 26, 2007; and  the Cochrane Central Register of Controlled Trials Register (CENTRAL) through the second quarter of 2006 were performed. The pharmaceutical manufacturers of granulocyte CSFs (G-CSFs) and granulocyte macrophage CSFs (GM-CSFs) also were contacted.

INCLUSION CRITERIA: Patients randomly were assigned to CSFs or to placebo or no therapy. CSFs were given concurrently with or after initiation of chemotherapy or conditioning for stem cell transplantation but before neutropenia developed. Chemotherapy or conditioning regimens or other supportive care was not planned to systematically differ between study groups.

FINAL NUMBER STUDIES INCLUDED = 148 RCTs

TOTAL PATIENTS INCLUDED IN THE REVIEW: 16,839 participants or cycles; 8,474 randomly were assigned to CSF and 8,365 to placebo or no treatment.

KEY SAMPLE CHARACTERISTICS: The RCTs included adult or pediatric patients with cancer undergoing chemotherapy or HSCT. The results were analyzed at the study level, not at the patient level.

Compared with the control, prophylactic CSFs did not significantly affect

• Overall all-cause mortality (7.6 % rate in the CSF group and 8.0% in the control group)
• Risk for infection-related mortality (3.1% rate in the CSF group and 3.8% in the control group).

Compared with the control, prophylactic CSFs significantly reduced

• Documented infections by 15%
• Microbiologically documented infections by 14%
• Clinically documented infections by 25%
• Episodes of febrile neutropenia by 29%
• Duration of febrile neutropenia by a mean difference of 1.38 days
• Duration of fever by a mean difference of 0.45 days
• Time to absolute neutrophil count (ANC) of 500 cells/mcL or more by a mean difference of 3.79 days
• Time to ANC of 1,000 cells/mcL or more by a mean difference of 5.03 days
• Duration of parenteral antibiotic therapy by a mean difference of 1.81 days
• Duration of hospitalization by a mean difference of 2.41 days.

The median rate of febrile neutropenia in the placebo groups was 44.2% versus 25.3% in the CSF groups.

The use of G-CSFs had a greater effect than the use of GM-CSFs on reducing documented infections and febrile neutropenia, but all-cause mortality and infection-related mortality did not differ.

The purpose of this study was to examine colony-stimulating factors (CSFs) given to children with cancer prophylactically after initiation of chemotherapy prior to the development of febrile neutropenia.

OVID MEDLINE (January 1966 to July 2003) and EMBASE (January 1980 to July 2003) databases were searched. The search was limited to randomized, controlled trials (RCTs) that included children 18 years and younger. References were hand searched for relevant literature, and conference proceedings from meetings of the American Society of Hematology, American Society of Clinical Oncology, Society Internationale Oncologie Pediatric, and the American Society of Pediatric Hematology/Oncology from January 2001 to January 2003 were reviewed. Manufacturers of G-CSF and GM-CSF were contacted.

16 RCTs. Five studies evaluated GM-CSF, and 11 examined G-CSF.

1,183 children, 592 of whom were randomized to CSF and 591 to the control arm.

In children with cancer:

• CSFs reduced the rate of febrile neutropenia by 20%.
• CSFs reduced hospitalization duration by two days.
• CSFs reduced the documented infection rate by 22%.
• CSFs reduced the duration of neutropenia by four days.
• CSFs reduced the rate of amphotericin use by 50%.
• CSFs were not associated with a reduction in infection-related mortality.
• CSFs were not associated with a difference in duration of parenteral antibiotics.
• CSFs were not associated with a difference in the duration of chemotherapy delay.

The rates of febrile neutropenia in all of the included studies were 39% or higher, so the researchers concluded that prophylactic CSFs should be used in children with cancer who are receiving chemotherapy with an anticipated rate of febrile neutropenia 40% or higher. No explicit measurement of quality of life exists, but researchers hypothesize that decreasing hospitalization and febrile neutropenia would contribute to improved quality of life.

To assess whether perioperative intravenous flurbiprofen axetil reduces postmastectomy pain syndrome

Patients were randomized to receive either 50 mg of flurbiprofen axetil 15 minutes before surgical incisions and six hours after or 5 ml of intralipid as a control. All patients were receiving unilateral breast surgeries and lymph node dissections for breast cancer. All patients received the same anesthesia protocol for postoperative patient-controlled analgesia with fentanyl for 48 hours. Pain and opioid dose were recorded at two, six, 12, 24, and 48 hours after surgery. Chronic pain assessments were done by telephone at two, four, six, and 12 months after surgery.

• N = 60
• MEAN AGE = 49.9 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Breast cancer
• OTHER KEY SAMPLE CHARACTERISTICS: All patients received chemotherapy, and none received radiation therapy.

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

• PHASE OF CARE: Active antitumor treatment

Double-blinded, randomized, controlled trial

• 11-point Numeric Rating Scale (NRS) for pain

About a third of patients had mild to moderate pain two months after surgery with an average score of 0.77. Pain scores at all time points after surgery were lower in the flurbiprofen group (p < 0.02). These differences were most pronounced at two, four, and six months. The incidence of pain also was consistently lower in the flurbiprofen group at all time points and significantly lower at two, four, and six months (p < 0.02).

Perioperative infusion with flurbiprofen axetil was associated with the the reduced incidence and severity of chronic postmastectomy pain during the first year.

• Small sample (< 100)
• Unintended interventions or applicable interventions not described that would influence results
• Measurement validity/reliability questionable
• Other limitations/explanation: The single NRS used for pain measurement was limited. No information was provided about analgesic use during the follow-up period.

Although there were limitations, the results of this study were promising, and it was possible that perioperative flurbiprofen could be beneficial in reducing chronic postmastectomy pain by reducing inflammatory mechanisms. Additional research in this area is warranted.

Databases searched were MEDLINE, EMBASE, Cochrane Collaboration, and BIOSIS.

Search keywords were octreotide, somatostatin, and diarrhea.

Studies were included in the review if they were randomized clinical trials (RCTs) with with one group receiving octreotide.

Exclusion criteria was not specified.

• A total of 37 references were retrieved.
• Quality grading was done using the Jadad scale.  Odds ratio analysis was used.

• Eight studies were included in the final review, representing 572 patients. The sample range across studies was 16–315.
• Five studies involved chemotherapy, and three studies involved radiotherapy.

All patients were undergoing the active treatment phase of care.

• Octreotide was effective compared to placebo (overall response [OR] = 4.9, 95% confidence interval [CI], 1.58–15.2).
• With radiotherapy-induced diarrhea, octreotide OR = 1.64 (95% CI, 0.53–5.08) and the test for overall effect was not significant. 
• For chemotherapy-induced diarrhea, OR =14.7 (95% CI,  4.06–53.26) and the test for overall effect was significant (p < 0.0001).
• The radiotherapy data showed high heterogeneity.
• The OR of octreotide was higher when used for treatment rather than prophylactically. However, only one trial evaluated prophylactic use.
• Most studies compared octreotide to loperamide.

Prophylactic use of octreotide did not show a statistically significant reduction in diarrhea. Octreotide did not reduce severity or incidence of diarrhea during pelvic radiotherapy, and some bowel functions appeared to be worse in the octreotide group. Octreotide showed significant benefit for the treatment of chemotherapy-induced diarrhea.

A limited number of studies were evaluated. No firm conclusions regarding prophylactic use can be made.

Findings support the use of octreotide for management of chemotherapy-induced diarrhea. Prophylactic use and use in patients with diarrhea because of pelvic irradiation are not supported. Nurses can advocate for appropriate use of octreotide in the management of diarrhea.

To investigate if prophylactic glutamine administration in patients receiving chemotherapy is effective for diarrhea prevention and control with the two major outcomes of duration and severity of diarrhea

• Databases searched were Embase, MEDLINE, Cochrane Library, and BIOSIS.
• Search keywords were glutamine, diarrhea, chemotherapy, meta-analysis, and prophylactic.
• Studies were included in the review if they used randomization, with one group receiving glutamine and one group serving as control, and if they included patients receiving bone marrow transplant.
• Studies were excluded if they were not written in English or Chinese or did not clearly report results.

• A total of 20 references were retrieved.
• Studies were graded using the Jadad 5-point scale with 1 point assigned to each of the following: description of study as randomized, description of appropriate method of randomization, description of double-blind, description of appropriate method of double-blinding, and statement addressing study withdrawals.
• Review Manager Software was used for quantitative analysis to calculate the odds ratio for the weighted mean differences (WMDs) for continuous data between the study drug group and the control group. The software also was used to perform heterogeneity analysis; data that was not significantly heterogeneous (p > 0.05) were analyzed using a fixed effects model, and heterogeneous data (p < 0.05) were analyzed using a random effects model.
• Common toxicity criteria grades for diarrhea were defined as follows.
  • Grade 0: No diarrhea
  • Grade 1: An increase of fewer than 4 stools per day from pretreatment
  • Grade 2: An increase of 4–6 stools per day or nocturnal stools
  • Grade 3: An increase of more than 6 stools per day, incontinence, or need for parenteral support for dehydration
  • Grade 4: Physiological consequences requiring intensive care or death.  
     

• A total of eight studies were included in the review.
• The total sample size was 298 patients, with 147 in the treatment groups and 151 in the placebo groups. Sample ranges across all studies were 8–33 in the treatment groups (n = 18) and 8–33 in the placebo groups (n = 19).
• Cancer diagnoses were gastrointestinal, acute myeloid leukemia, colorectal, advanced breast, autologous and bone marrow transplant, and hematologic.

Patients were undergoing the active treatment phase of care.

• An overall statistically significant difference was found in duration of diarrhea with glutamine recipients versus patients receiving placebos (WMD, -1; 95% confidence interval [CI], -1.73, -0.26). Oral glutamine scored higher (WMD, -1.06, 95% CI, -2.01, -0.11) compared to intravenous glutamine (WMD, -0.89; 95% CI, -2.07, 0.28).
• Study findings indicated that glutamine did not improve the severity of diarrhea (WMD, 0.49; 95% CI, -1.36, 0.39).
• Statistical heterogeneity was found for overall rates (p < 0.00001) with the random effects model (p < 00001).

According to the results of this meta-analysis, prophylactic administration of glutamine (ranging from 16–30 g oral form daily for periods of up to 20 days and 20-40 g IV administration daily for periods of up to 21 days) reduced the length of chemotherapy-induced diarrhea (CID). However, results did not show reduction in the severity of the diarrhea. Oral glutamine was found to be more effective than IV glutamine.

• Endotoxin levels were used to assess permeability levels instead of the standard lactulose-mannitol test.
• Although this was a meta-analysis, the individual RCTs were small.
• Doses and administration were not standardized across studies, making it difficult to combine results for statistical analysis.

This meta-analysis provided evidence that glutamine, as the most abundant amino acid in humans, could reduce the duration of CID and intestinal permeability and may stimulate mucosal recovery. However, glutamine has not been shown to be beneficial in reducing or limiting the severity of CID. Larger trials are needed.

Prophylactic oral glutamine in patients receiving chemotherapy may be useful in lessening the duration of chemotherapy-related diarrhea. However, without further large trials with standardized doses, routes, and length of administration, glutamine should not be recommended for practice.

To test the effectiveness of an overall supportive and psychoeducational care intervention on caregiver quality of life and patient symptoms

A quality of life assessment was conducted at baseline for patients and caregivers. Results were used to develop a palliative care plan that was discussed at weekly meetings by the interdisciplinary care team. Symptom management and supportive care referrals and community resources were identified as needed. Family caregivers also received four educational sessions and a manual of all teaching content. Questionnaires were completed at baseline, 6, and 12 weeks. A comparison usual care group was recruited after the intervention group and had study measures obtained at baseline and at 7 and 12 weeks.

• N = 354 caregiver and patient pairs   
• MEAN AGE = 57.3 years
• MALES: 37.3%, FEMALES: 66.7%
• KEY DISEASE CHARACTERISTICS: All patients had lung cancer.
• OTHER KEY SAMPLE CHARACTERISTICS: Of the patients, 15.3% were Asian, 4.5% were Black, and 6.7% were Hispanic or Latino. About one-third were employed.

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: Southern California

PHASE OF CARE: Late effects and survivorship

Prospective, nonrandomized, parallel-group trial

• City of Hope quality of life tool
• Montgomery Borgotta Caregiver Burden Scale
• Preparedness for Caregiving Scale
• Functional Assessment of Cancer Therapy-Lung (FACT-L) for patient quality of life and symptoms
• Functional Assessment of Chronic Illness-Spiritual Well-Being Scale (FACIT-Sp)
• Distress Thermometer

Caregivers in the experimental group had improved quality of life in the social well-being domain (p < 0.001) and distress (p = 0.01). Caregivers in the intervention group reported less problem with objective burden or life disruption (p < 0.001).

The palliative care intervention provided here was associated with lower caregiver strain and burden in some aspects compared to those who did not receive the intervention.

• Risk of bias (no blinding)
• Risk of bias (no random assignment) 
• Risk of bias (no appropriate attentional control condition)
• Usual care was not fully described.

The findings were limited because of study design; however, the findings support the benefit of palliative care for caregivers.