To evaluate the effectiveness and safety of adding metoclopramide to the standard ondansetron and dexamethasone antiemetic regimen for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV) among patients receiving cisplatin-based therapy

Patients were randomized (stratified by gender and age group) to a treatment or control group. All patients received ondansetron and dexamethasone prior to cisplatin and on the four subsequent days (days 2-5). Patients received either 20 mg of metoclopramide or placebo orally four times daily on days 2-5. Rescue treatment (including metoclopramide) was allowed based on the decision of the primary physician. On day 2, blinded data collectors documented the first emetic episode and frequency of emesis, severity of nausea and vomiting, side effects, and rescue antiemetic medications. On day 5, patients reported satisfaction of emetic treatment and quality of life.

• The study consisted of 162 patients.
• Just more than half (51%) of patients were 50 years old or older.
• The sample was 73% male and 27% female.
• The majority of patients (74%) had been diagnosed with head and neck cancer. Other cancers included gastrointestinal tract (10%), lung (5%), and sarcoma (5%).
• All patients received more than 50 mg/m² of cisplatin for their first dose.

The study was conducted at a single site, inpatient setting in Thailand.

All patients were in active antitumor treatment.

This was a randomized, double-blinded, placebo-controlled study.

• Measurement instruments for the first emetic episode, frequency of emesis, side effects, and rescue antiemetic medication were not reported in the article. 
• Common Terminology Criteria for Adverse Events, version 3.0, was used to measure severity of nausea and vomiting. 
• The Functional Living Index Emesis was used to document patient-reported satisfaction and quality of life.

• Before random assignment to the study, significantly more patients in the placebo group (30%) required rescue antiemetic medication for treatment of acute emesis (p = 0.04), and significantly more placebo group patients received metoclopramide as a rescue antiemetic (p = 0.02).
• No differences were found among treatment and placebo groups for patients who developed CINV, the severity of CINV, time to first emetic episode, or impact of CINV on daily life.  The only difference noted between groups was the proportion of patients that required rescue antiemetic medication, with significantly less medication used in the treatment group versus the placebo group (p = 0.05). 
• Metoclopramide was well tolerated with no difference in toxicities among the two groups.  Only one patient receiving metoclopramide had extrapyramidal effects.

No antiemetic benefit was found by adding metoclopramide to the standard ondansetron and dexamethasone regimen during cisplatin-based therapy; however, results are difficult to interpret because of a significant number of control patients receiving metoclopramide prior to the start of the study.

• Notable baseline sample group differences existed.
• Patients were allowed to receive metoclopramide for treatment of acute emesis prior to study randomization; therefore, some patients in the placebo group received metoclopramide and were not technically a control group.

A high number of patients in the placebo group developed anticipatory vomiting prior to the start of treatment, which illustrates the importance of performing thorough assessments prior to the start of chemotherapy and providing education prior to the start of the next course of chemotherapy.

To investigate potential analgesic benefits of 4 g paracetamol daily for palliative patients with cancer requiring high-dose opioids

Patients received usual medications plus 4 g paracetamol or placebo for five days each in random order. Primary outcome, effect on pain, was assessed using daily diaries, including a numeric rating scale ranging from 0 (no pain) to 10 (unbearable pain) and recording numbers of breakthrough analgesics. Patients also indicated in which part of the study their pain was better controlled.

• The study reported on 22 patients who completed the study.
• Mean patient age was 56.3 years (range = 28–79 years).
• The sample was 55% male and 45% female.
• Patients had a variety of cancer types.
• Baseline pain score was greater than or equal to 2, and patients were using at least 200 mg daily morphine equivalents.

• Multisite
• Both inpatient and community-based patients from Brisbane South Palliative Care Service and Mt. Olivet Palliative Care Service in Brisbane, Australia

The study used a randomized, double-blind, placebo-controlled, crossover design.

• Numeric rating scale (0–10)
• Patient-generated daily diary
• Mini-Mental State Examination

There were no significant order or treatment-by-the-order interaction effects for any variable. There were no significant differences in pain when assessed with placebo compared with paracetamol. No change approached clinically significant levels, with a mean difference in rated pain of 0.16, and mean difference of 0.42 for a number of breakthrough medications. Fifteen patients were undecided whether paracetamol improved pain.

Data from this study do not support the common practice of adding regular paracetamol (acetaminophen) daily to high-dose opioids to enhance pain control in the palliative setting.

The study had a small sample, with less than 30 participants.

There is a growing body of evidence suggesting that some patients do not receive any additional benefit from adding paracetamol or acetaminophen to strong or high-dose opioids. Pain management interventions should be individualized. Unwarranted exposure to potential side effects/toxicities and costs should be avoided when possible by eliminating paracetamol or acetaminophen in those individuals in whom no benefit has been demonstrated.

To compare two techniques for pain relief with ​transrectal ultrasonography (TRUS)-guided biopsies

Patients undergoing prostate biopsies were randomized to receive either local infiltration anesthesia alone or a combination of local anesthesia and lignocaine 5% ointment to the anal rind, canal, and anterior rectal wall. Patients were asked to rate pain during insertion, during infiltration, and after biopsy.

• N = 163
• MEAN AGE = 61.7 years (range = 50–88 years)
• MALES: 100%         
• KEY DISEASE CHARACTERISTICS: All had elevated prostate-specific antigens

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

• PHASE OF CARE: Diagnostic

Randomized trial

• 100 mm Visual Analog Scale (VAS) for pain

Patients who received a combination of local and topical anesthesia reported significantly less pain (p = 0.005) at all stages of the procedure.

The combination of a local anesthetic infusion with a topical anesthetic may provide better pain control during biopsy.

• Risk of bias (no blinding)
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Other limitations/explanation: Data regarding pain differences were reported using different numeric scales, so the actual method of measurement and resulting analysis was unclear. It was unclear how patients during biopsy could reasonably use the VAS to report pain.

The combination of anesthetic infiltration and a local topical anesthetic may reduce pain during biopsy.

To determine whether a needleless closed system (NCS) is superior to the Luer cap system (LCS) in regards to the prevention of catheter-related bloodstream infection.

This was a retrospective study comparing the length of time from central venous catheter (CVC) insertion to the development of central-line associated blood stream infection (CLABSI) using LCS and then switching to NCS.

• N = 495
• AVERAGE AGE = 64.4 years
• MALES: 312/495 (63%), FEMALES: 183/495 (37%)
• KEY DISEASE CHARACTERISTICS: Colorectal cancer

• SITE: Single-site  
• SETTING TYPE: Multiple settings  
• LOCATION: Tochigi, Japan

• PHASE OF CARE: Active antitumor treatment

Retrospective analysis

The authors measured the time interval from CVC insertion to the development of CLABSI and compared a group of patients using LCS to a group using NCS. Centers for Disease Control (CDC) guidelines were used to define and diagnose CLABSI.

Using the Kaplan-Meier estimate and the log-rank test, the authors found that there was no significant difference between the LCS group and the NCS group in the time interval from CVC insertion to onset of CLABSI. Similarly, there was no significant difference in the incidence of CLABSI (p = 0.3), blood culture positivity (p = 0.836), and CVC tip positivity (p = 0.116) between the two groups.

There was no significant difference between the two groups in regard to blood culture positivity, CVC tip culture positivity, or the incidence of CLABSI. NCS did not demonstrate superiority in terms of prevention of CLABSI.

• Baseline sample/group differences of import
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement/methods not well described
• Other limitations/explanation: There was a significant difference in sample size between the LCS and NCS groups; the authors also note significant differences between the two groups regarding gender, length of inserted catheter, duration of catheter insertion, use of surgery, chemotherapy administration, and administration of parenteral nutrition.

Although they were not shown to reduce CLABSI, NCSs are still recommended as a means of preventing needle-stick injuries.

• To perform a retrospective review of medical records to determine the use of prophylactic laxatives in patients receiving opioids.
• To determine the incidence of constipation in patients taking opioid medications.
• To promote use of preventative medications by educating physicians, checking orders, and educating patients.

In part 1, patients who were admitted and receiving opioids were surveyed for use of prophylactic laxatives to prevent constipation.

In part 2, prescribers were given drug information, orders were reviewed, and patients were educated about laxatives to manage constipation.

• The study reported on a sample of 83 patients with cancer in part 1 and 107 patients with cancer in part 2. 
• Mean patient age was 66.1 years (range 41-92) in part 1 and  63.7 years (range 14-83) in part 2. 
• The sample comprised 40 women and 43 men in part 1, and 40 women and 67 men in part 2.

• Single site
• Inpatient
• Japan

Patients were undergoing the active treatment phase of care.

This was a retrospective survey followed by an interventional study.

• National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 3.0
• Constipation medical records were reviewed.

• Of the 83 patients, 57% (47 patients) received laxatives with opioids.
• Patients who did not receive laxatives had a higher incidence of constipation than those who received laxatives (56% versus 21%, p = 0.0024).
• Patients who received laxatives had more bowel movements in seven days than patients who did not (5.6 versus 3.9, p = 0.005).
• Taking more laxatives resulted in less constipation, and the absence of prophylactic laxatives resulted in an increased risk of constipation.
• The incidence of constipation was lowest in patients who received prophylactic combination treatment with magnesium oxide and pantethine.

Laxative use prophylactically reduced the incidence of constipation in patients taking opioid therapy but did not completely prevent it.

• The study lacked an appropriate control group.
• Part 1 had fewer than 100 patients.
• The validity and reliability of medical records for determination of laxative use was questionable, and patients did not self-report use.

Laxative prophylaxis is beneficial to reduce the risk of opioid-induced constipation. Proactive interventions to increase laxative use may be beneficial to patients.

To evaluate the effectiveness of prophylactic laxatives and antiemetics on constipation, nausea, and vomiting in patients with cancer receiving opioids for the first time.

Medical records were reviewed from 2009 to 2010 for patients experiencing constipation, nausea, or vomiting during the first week of opioid analgesic administration. Number of stools recorded was used in the analysis. Constipation was defined as a stool-free interval of at least 72 hours during the first week. One episode of vomiting was counted as evidence of vomiting. Nausea grading was recorded for seven days.

• The study reported on a sample of 619 patients.
• Mean patient age was 66.8 years (range 53-81).
• The sample was 63% male and 37% female.
• Gastrointestinal and lung cancer were most prevalent, but the sample included a variety of disease sites.
• Most patients were receiving extended-release oxycodone.
• Patients were excluded if they were using transdermal opioids; undergoing surgery within the first week of receiving opioids; or experiencing continuous symptoms of constipation, nausea, or vomiting prior to opioid administration.

• Multi-site
• Setting type not specified
• Japan

• Patients were undergoing multiple phases of care.
• The study has clinical applicability to older adult and palliative care.

This was a descriptive, retrospective study.

National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE), version 4.0, for nausea grading

• Incidence of constipation was 33.7% in those receiving prophylactic laxatives, compared to 54.6% in others (p < 0.001).
• The most frequently used laxative was magnesium oxide. Some patients also received senna and other combined laxatives. 
• No significant differences in efficacy existed among different laxatives.
• Regression analysis showed that no laxative use, use of morphine formulation, and being aged 70 years or older were predictive of constipation (p < 0.01).
• Odds ratio in favor of laxatives was 0.469 (95% confidence interval [0.231, 0.955], p = 0.037).
• No effects were observed for use of prophylactic antiemetics on nausea or vomiting. Antiemetics used were prochlorperazine, domperidone, and metoclopramide.

Use of prophylactic laxatives in patients receiving opioids for the first time was effective in reducing the risk and prevalence of constipation.

• A risk of bias existed because of the lack of random assignment.
• Measurement validity and reliability were questionable.
• The descriptive study design with dependence on medical record documentation limited the data's reliability.
• The duration of observation was short at only one week. Longer term efficacy is not known. 
• Dosages of opioids and other factors that could have contributed to constipation were not described.

Findings suggested use of prophylactic laxatives can reduce opioid-induced constipation during the first week in which patients receive opioids. Findings also suggested older patients may be at greater risk for opioid-induced constipation. Nurses can ensure that prophylactic regimens to prevent constipation are suggested for patients beginning opioid use and older adult patients.

To gain evidence regarding which regimen should be used for the management of highly emetogenic chemotherapy (HEC) induced chemotherapy-induced nausea and vomiting (CINV)

Patients were randomly assigned to the order of receiving either palonosteron and dexamethasone (PD) or aprepitant, granisetron, and dexamethasone (AGD) prophylaxis. The PD regimen was 0.75 mg palonosetron and 13.2 mg dexamethasone IV prior to treatment and 8 mg oral dexamethasone 24 and 48 hours later. The AGD regimen was 125 mg oral aprepitant and 3 mg granisetron and 6.6 mg dexamethasone IV before treatment, followed by 80 mg aprepitant and 4 mg dexamethasone at 24 and 48 hours. During the second cycle, patients were crossed over to the alternative regimen. During cycle 1, CINV and the use of rescue antiemetics were evaluated. After crossover, patients were asked which treatment was more effective and preferred. Rescue medications were metoclopramide or prochlorperazine.

• N = 84   
• MEDIAN AGE = 64.5 years
• AGE RANGE = 30–77 years
• MALES: 79.8%, FEMALES: 20.2%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Most patients had stage IV disease
• OTHER KEY SAMPLE CHARACTERISTICS: All patients were chemotherapy naïve and were scheduled to receive two or more cycles of chemotherapy including cisplatin at 60 mg/m² or more.

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

• PHASE OF CARE: Active antitumor treatment

• Randomized crossover trial

• Common Terminology Criteria for Adverse Events (CTCAE)
• Functional Living Index-Emesis (FLIE) questionnaire
• Complete response rate for acute, delayed, and overall phases defined as no emesis and no use of rescue medications

No significant differences existed between treatment regimens for complete response in the acute phase. The complete response (CR) rate was higher in the delayed (p = 0.025) and overall phases (p = 0.025) in the regimen including aprepitant. Less than 40% with either treatment had no nausea. FLIE scores indicating impact on daily life showed that more patients in the aprepitant-based regimen group were not affected by nausea (p = 0.014). Forty-one percent indicated preference for AGD, 19.7% preferred PD, and 39.3% indicated no preference.

Findings suggest that a CINV prophylactic regimen containing an NK1—in this case, aprepitant—was more effective in preventing CINV than a regimen of palonosetron and dexamethasone alone.

• Data collection methods for response rates were not reported.

Findings support the use of a triple drug regimen of a 5HT3, NK1, and dexamethasone for patients receiving HEC. Nausea in the delayed phase continues to be an ongoing problem that is not completely relieved with these regimens. Further research is needed to identify other adjuvant medications to address nausea.

To evaluate the effectiveness of calcium/magnesium (Ca/Mg) infusions in reducing the incidence and severity of oxaliplatin-related neurotoxicity and to evaluate the effects of Ca/Mg infusions on progression-free survival and platinum plasma levels in patients with colorectal cancer

Patients with metastatic colorectal cancer were randomized and double-blinded to receive mFOLFOX6 with a Ca/Mg infusion (100 ml of 5% glucose-containing calcium gluconate of 850 mg and magnesium sulfate of 720 mg) before and after the administration of oxaliplatin or mFOLFOX6 with placebo (100 ml of 5% glucose alone) before and after administration of oxaliplatin (85 mg/m²) every two weeks for six cycles. Prior to administration, patients were assessed for adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE), version 3.0, by nurses or pharmacists.

• N = 33 (17 [Ca/Mg group], 16 [control group])
• MEAN AGE = 63 years (Ca/Mg group), 64 years (control group)
• MALES: 49%, FEMALES: 51%
• KEY DISEASE CHARACTERISTICS: Histologically confirmed colorectal cancer with either unresectable metastasis or prior resection of metastatic lesions
• OTHER KEY SAMPLE CHARACTERISTICS: Bone marrow, liver, and kidney function normal in all subjects; World Health Organization performance status of 0–2; no multiple cancers or history of radiotherapy; no differences in age, sex, number of mFOLFOX6 cycles, relative dose intensity, or number of metastatic organs between placebo and Ca/Mg group

• SITE: Single site
• SETTING TYPE: Outpatient
• LOCATION: Japan-Saitama Medical Center

• PHASE OF CARE: Advanced
• APPLICATIONS: Elder care, palliative care 

Prospective, randomized, double-blind, controlled trial in patients with metastatic colorectal cancer receiving mFOLFOX6

• Adverse events were evaluated by nurses and pharmacists before the start of administration according to the CTCAE, version 3.0, and DEB-NTS, although only the data from baseline and after six cycles were provided.
• Response Evaluation Criteria in Solid Tumors (RECIST) criteria was used to evaluate treatment outcomes and compare between groups.
• Plasma platinum levels (blood samples) were drawn five minutes, one hour, three hours, and two weeks after the first cycle and five minutes, one hour, and two weeks after the fifth cycle for comparison.

Ca/Mg infusion prior to and after mFOLFOX6 did not reduce the incidence of grade 1–3 neurotoxicity using two different standardized measures for neurotoxicity (DEB-NTS and CTCAE) after the completion of six cycles; response rates, disease control rates, and median survival times were not significantly different between groups. No significant differences existed in the plasma platinum levels between groups (Ca/Mg versus placebo) at any time point using the pre-established significance value of p < 0.05. Also, no significant difference in plasma platinum levels existed in those who developed grade 2 neuropathy compared to those who developed less severe neuropathy (DEB-NTS). When comparing those who achieved a partial or complete remission with mFOLFOX6 to those who achieved no response, plasma platinum levels did not differ, suggesting that calcium and magnesium infusions did not influence the efficacy of mFOLFOX6 chemotherapy.

Ca/Mg infusions before and after oxaliplatin did not reduce the incidence or severity of neurotoxic symptoms in patients with metastatic colorectal receiving mFOLFOX6.

• Small sample (< 100)
• Risk of bias(sample characteristics)
• Findings not generalizable
• The study was terminated prematurely prior to completion of enrollment because of an interim analysis of the CONCEPT study reporting that treatment with Ca/Mg decreased antitumor activity.
• No explanation of history or presence of neurotoxic symptoms prior to the start of treatment for either group
• Unclear if patients were on medication or treatment for neuropathy
• Limited information for inclusion/exclusion criteria
• Unclear if all patients completed six cycles of mFOLFOX6
• Mann-Whitney test comparing continuous variables has limited statistical inference.
• No reliability or validity information provided for the primary measure of neuropathy (NEB-NTS)
• Lack of power to detect statistical significance because of small sample size

The administration of Ca/Mg before and after oxaliplatin as a preventive measure to reduce the incidence or severity of oxaliplatin-related peripheral neuropathy in patients with colorectal cancer receiving mFOLFOX6 for six cycles has no clinical benefit.

To investigate the effects of single-dose versus multiple-dose antimicrobial prophylaxis on surgical site infections (SSI) in patients undergoing elective surgery for rectal cancer

All patients received a preoperative bowel cleansing, kanamycin and erythromycin orally within 24 hours prior to surgery, and 1 g of a second-generation cephalosporin IV perioperatively. After surgery, patients were randomized to receive either single-dose prophylaxis one hour after surgery or an additional five doses over two consecutive days. Wounds were inspected daily in the hospital and in the clinic 30 days after surgery. The trial was designed to detect a 10% difference in the incidence of SSIs between groups.

• N = 279  
• MEAN AGE = 65 years (range = 33–91 years)
• MALES: 64.5%, FEMALES: 35.5%
• KEY DISEASE CHARACTERISTICS: All patients had rectal cancer; the majority had anterior resections
• OTHER KEY SAMPLE CHARACTERISTICS: None of the patients had preoperative chemotherapy or radiation therapy.

• SITE: Single-site    
• SETTING TYPE: Multiple settings    
• LOCATION: Japan

• PHASE OF CARE: Active antitumor treatment

Noninferiority randomized, controlled trial

• SSIs were recorded according to Centers for Disease Control (CDC) definitions for incision site and organ/space infections

The incidence of incision site infections was 5% in the single-dose group and 7.1% in the multiple-dose group. Organ/space infections were 10.8% in the single-dose group and 8.6% in the multiple-dose group. Several organ/space infections were related to anastomotic dehiscence. Overall, the incidence of SSIs was 13.7% with single-dose prophylaxis and 13.6% with multiple-dose prophylaxis. Subgroup analysis by specific surgical procedure did not show any significant differences between groups.

Single-dose, postoperative, intravenous, antimicrobial prophylaxis demonstrated similar results to that of multiple-dose prophylaxis. Multiple antimicrobial doses did not show improved benefit for the prevention of surgical site infections

• Risk of bias (no blinding)

A single dose of IV antibiotic prophylaxis after rectal surgery for cancer had similar outcomes to that of multiple postoperative antibiotic doses. These findings show there is no benefit to more doses of prophylactic postoperative antibiotics for the prevention of SSIs.

Patients were assigned randomly to receive either placebo or interleukin-11 (IL-11) 50 mcg/kg/day subcutaneous (SC). The study drug was blinded. Randomization was stratified by investigative site and also by whether patients had received any prior chemotherapy. SC administration began on day two and was given for a minimum of 10 days after the first cycle of chemotherapy.

• N = 77     
• AGE: Older than 18 years of age
• WOMEN: 100%
• KEY DISEASE CHARACTERISTICS: Stage 2, 3, or 4 breast cancer and Eastern Cooperative Oncology Group (ECOG) status of 0–2
• OTHER KEY SAMPLE CHARACTERISTICS: Patients treated with cyclophosphamide (3200 mg/m²) and doxorubicin (75 mg/m²) IV on same day; chemotherapy repeated every 21–28 days

• Randomized, blind study

• The primary endpoint was whether a patient required platelet transfusions during two cycles of chemotherapy.
• Time to platelet recovery, open-label treatment, tumor response, time to neutrophil recovery, antibody development, safety, and efficacy

Sixty-seven patients were assessable. Sixty-eight percent of patients in the IL-11 group did not receive transfusions, versus 41% in the placebo group (p = .04). The IL-11 group had a decreased total number of platelet transfusions (p = .03) and time to platelet recovery to greater than 50K in the second cycle (p = .01). Side effects in the IL-11 group (p < .05) were peripheral edema (68%), dyspnea (48%), pleural effusion (18%), and conjunctival infection (25%).

• All female patients
• Only high-risk and advanced
• Well-controlled
• Did not demonstrate for dose intensity, maintenance of planned schedules
• Open-label so everyone could crossover
• Did not address how people stayed on track for schedule
• IL-11 for first two cycles
• How many women went on to get planned schedules?
• Where was the science in 1997?