DOI Link: http://apjcn.nhri.org.tw/server/APJCN/17/1/17.pdf

To evaluate the effects of a Taiwanese traditional diet including paeony and licorice components on pain in patients with terminal cancer

Patients were randomly assigned to one of three groups: (a) Taiwanese traditional herbal diet (TTHD) group, consisting of analgesic herbs (paeony root and licorice root) and tonic vegetable soup (lilli bulbus, nelumbo seed, and jujube fruit), (b) reference group, receiving the regular hospital diet, (c) and control group, receiving the tonic soup without addition of analgesic herbs. All patients remained on the assigned diet for one week. Pain was assessed via patient self-report questionnaire on days 3 and 10.

• The study reported on a sample of 2,466 patients.
• Patient age ranged from 9 to 89 years; 87% were between 40–79 years old.
• The sample was 50.7% male and 49.3% female.
• A variety of cancer sites were included, with the most common being lung, liver, colorectal, and stomach.
• An estimated 90% of patients had pain that was from medical conditions other than cancer. Most patients had neuropathic pain.
• Patients on any analgesics were excluded from the study.

• Single site
• Inpatient setting
• Taiwan University Palliative Medicine Ward

The study was a randomized, parallel group trial.

• Numeric rating scale using a 100-point scale: without pain, minimal pain, mild but tolerable pain, moderately uncomfortable pain, and extreme pain
• Previous tool validation identified
• No information on reliability

All groups reported significant reduction in mean pain scores on days 3 and 10. Patients in the TTHD group reported a three-point improvement in pain (from 53 to 50), which was significantly greater than that in the reference and control groups (p < 0.01).

In this study, use of traditional Taiwanese analgesic herbs was effective for pain reduction, compared to control and reference groups, in palliative care patients who were not receiving other analgesic medications.

Patients on analgesics were excluded from this study, and authors stated that in 90% of cases, pain was not cancer-related. Application of findings to other groups with cancer-related pain who require substantial analgesic therapy is questionable. Though statistically significant, the clinical relevance of the change in average pain scores is questionable, with a change of 3 points on a 100-point scale. The pain scale is not clearly explained, and it appears its scoring is not a continuous variable, though the statistical analysis and summary data provided treats the data as continuous data.

Findings here suggest that traditional Taiwanese analgesic herbs may be helpful in managing pain in terminally ill patients. There are a number of study report issues that make these findings very limited, so applicability to other patients with cancer-related pain is questionable. Future research in this area should examine use of this approach as adjunctive therapy in concert with other analgesia in patients with pain that is truly cancer-related. Applicability in other cultures is needed.

DOI Link: doi: 10.1177/0148607116651509

To evaluate the efficacy and safety of early supplementary parenteral nutrition (PN) following esophagectomy

Patients who had undergone scheduled esophagectomy (by laparoscopy or open surgery) for esophageal cancer were randomized 1:1 into two groups. The randomization sequence was generated by a computer, and the code was kept in sealed envelopes. Both groups were started on enteral nutrition (EN) within 24 hours after surgery; patients in the EN plus PN group also received supplementary parenteral nutrition (SPN), gradually increased over five days, to meet the full caloric target.

• N = 70   
• AGE = 30–66 years
• MALES: 68%, FEMALES: 32%
• CURRENT TREATMENT: Surgery
• OTHER KEY SAMPLE CHARACTERISTICS: Esophagectomy, nasojejunal tube placement or jejunostomy for postoperative feeding

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: Department of Thoracic Surgery of Zhongshan Hospital, China

• PHASE OF CARE: Active Antitumor Treatment
• APPLICATIONS: Elder care

Randomized trial

The full-calorie target for each patient was based on measured resting energy expenditure, as determined by open-circuit indirect calorimetry (IC) (QUARK RMR). IC measurements were performed daily on each patient in both groups. The Chinese version of the Medical Outcome Study 36-Item Short-Form (MOS SF-36) as a surrogate of health-related quality of life assessment was used, and patients were required to fulfill the scale before surgery. Anthropometric parameters were taken. Standard laboratory blood biochemistry parameters were measured. Perioperatively, tumors were staged using the International Union Against Cancer's sixth edition of the tumor node metastasis (TNM) classification of malignant tumors (www.uicc.org) according to postoperative pathological results. The Clavien-Dindo classification was used to grade and record postoperative complications.

Patients in the EN plus PN group but not in the EN group preserved body weight (mean = 0.18, SD = 3.38 kg versus mean = −2.15, SD = 3.19 kg; p < 0.05) and FFM (mean = 1.46, SD = 2.97 kg versus mean = −2.08, SD = 4.16 kg) relative to preoperative measurements. Length of hospital stay, postoperative morbidity rates, and standard blood biochemistry profiles were similar. However, scores for physical functioning (mean = 71.5, SD = 24.3 versus mean = 60.4, SD = 27.4; p < 0.05) and energy/fatigue (mean = 62.9, SD = 19.5 versus mean = 54.2, SD = 23.5; p < 0.05) were significantly higher in the EN plus PN group 90 days following surgery.

Addition of early PN to supplement standard EN did not significantly change the perioperative outcomes of patients undergoing esophagectomy. However, for patients who received SPN, increased calorie and protein intakes were associated with preservation of body weight, FFM, and better health-related quality of life in short-term follow-up. Additional studies with larger sample sizes are needed to confirm these findings.

• Small sample (< 100)
• Key sample group differences that could influence results
• Exclusion criteria study included (a) aged younger than 18 years or older than 75 years, (b) body mass index less than 18 or greater than 30 kg/m², (c) contraindications for EN or PN, (d) preoperative initiation of EN or PN, (e) ongoing infections, (f) preexisting organ failure (e.g., renal dysfunction–required dialysis, noncompensatory chronic obstructive pulmonary disease), (g) treatment with high doses of steroids, and (h) severe metabolic abnormalities (e.g., diabetes, hyperthyroidism, hypothyroidism).

To evaluate the therapeutic effects of RhEGF on mucositis in patients with head and neck cancer receiving RT, with or without chemotherapy

Patients were randomized to 1 of 4 arms, 10, 50, or 100 mcg/mL study drug or placebo. Patients were instructed to spray study drug over the entire oral mucosa and then swallow the residual, twice daily, from the first day through week 5 of RT. Oral intake was restricted for 30 minutes after spraying. All patients gargled with chlorhexidine. No other mucositis treatment was allowed. Pain medication was allowed. Patients were removed from study if RT was interrupted for 3 or more consecutive days. Every week patients mucositis was graded by a radiation oncologist using RTOG scoring criteria. Patients with treatment delay were removed from the study

Sample Size: 100 patients Age Information: 18-77 years Females: 38 Males: 75 Diagnosis Information: head and neck cancer receiving at least 5 weeks of definitive aim RT or postop RT or definitive chemoradiotherapy. Fraction was 2.0 ± 0.25 Gy with 2 dimensional, 3 dimensional or IMRT Other Key Characteristics: exclusions included cytotoxic chemotherapy or RT within 3 weeks of the study or systemic or topical oral corticosteroids within 30 days of the study. Induction chemotherapy or concurrent cisplatin was allowed.

Multisite Korea

Randomized, double-blind, placebo-controlled phase 2. Randomized per institution and concurrent use of chemotherapy.

RTOG grading

RhEGF significantly reduced the incidence of severe oral mucositis at the primary endpoint (64% response with 50 mcg/mL EGF vs 37% response in the control group)(p =.025). Thirteen patients dropped out of the study. Six cases were dropped from the study due to radiotherapy interruption. Response rate ( ratio of patients who did no develop oral mucositis, with grade 2) were 57.7%, 64% and 59.1% for RhEGF groups. Only the group treated with 50mcg/ml had significantly higher response rate than placebo ( p =.0246). There were no significant differences between groups at week 4-5.

The EGF spray may have potential benefit for oral mucositis in patients undergoing RT for head and neck cancer. Phase 3 studies are ongoing to confirm these results.

It is difficult to standardize the administration of topical medications, also unable to penetrate the deep regions of the throat No intention to treat analysis of those removed from the study Variations if patients oral mucosal status and overall medical condition, only 5 weeks of observation, the dose was self-administered by patients and recorded in their log books, eating habits of Koreans differ from those of Western societies The spray did not effectively reach the pharyngeal mucosa, therefore there was no effect on pharyngeal mucositis. Patients had varying RT doses, some had IMRT and some had concurrent chemotherapy – there was no subgroup analysis based on these differences that could be expected to affect rate and severity of mucositis.

Due to topical spray administration, there is a potential for improper amount of drug to be administered. Phase 3 results should be reviewed if completed.

DOI Link: doi: 10.1016/j.ejca.2012.10.030

To test, in a randomized controlled study, the effect of a structured eight-week group mindfulness-based stress-reduction program on anxiety and depression among women with breast cancer

The mindfulness-based stress-reduction program consisted of eight weekly two-hour group sessions. The program included guided meditation, yoga and psychoeducational advice on stress and stress reactions, and group dialog about the integration of mindfulness practice into daily life. Three experienced clinical psychologists provided the program. The control group received usual care. Data were collected before randomization and at 6 and 12 months after the intervention.

• The study reported on 336 female patients (168 in the experimental group, 168 in the control group).
• Mean patient age was 54.14 years (SD = 10.30 years).
• Patients had stage I–III breast cancer (97% had stage I or II).
• Recruitment was of patients who had received surgery within 3–18 months. Patients underwent various treatments during the study.

• Multisite
• Outpatient setting
• Hospitals associated with University of Copenhagen, Denmark

• Patients were undergoing active antitumor treatment.
• The study has clinical applicability for elder care and palliative care.

A randomized controlled trial design was used.

• Symptom Checklist-90 Revised (SCL-90-R), Danish version: 13 items relating to the depression subscale and 10 items relating to the anxiety subscale
• Center for Epidemiologic Studies Depression Scale (CESD): 21 items focusing primarily on cognitive and affective, rather than physical, manifestations of depression

• At baseline, researchers noted no difference between groups in regard to clinical or demographic characteristics, depression, or anxiety.
• After intervention, analysis revealed a statistically significant between-group difference regarding CESD scores (p = 0.001). At six months, analysis revealed a significant between-group difference regarding anxiety scores (p = 0.05) and for both depression measures (SCL-90-R, p = 0.01; CESD, p = 0.03). After 12 months, researchers noted a significant difference between groups in regard to SCL-90-R depression and CESD scores. After 12 months, intention-to-treat analyses showed differences between groups in levels of anxiety (p = 0.0002) and depression (SCL-90-R, p < 0.0001; CESD, p = 0.0367).
• The intervention was more effective for those with higher levels of anxiety and depression at baseline.

The mindfulness-based stress-reduction program was effective in reducing anxiety and depression over time in the patients studied. The intervention was most effective for those who had higher levels of anxiety and depression at baseline.

• The study had risk of bias due to lack of appropriate attentional control.
• Key differences between the sample groups could have influenced results.
• The intervention is expensive, impractical to implement, and presents training needs.
• Researchers paid insufficient attention to the control group and provided no blind.
• Patients may have been at different time points in relation to treatment (e.g., chemotherapy, radiation treatment). This may decrease the reliability of study findings.

The intervention appears to be effective. It does, however, require that the facilitator receive special training, which is an extra cost, and the intervention may be difficult to implement in the practice setting. The study does not address whether the effectiveness of the intervention varies with phase of care. As with other types of intervention, the mindfulness-based stress-reduction program appeared to be most effective for patients who had higher levels of anxiety and depression at the beginning of treatment, suggesting that appropriate patient selection for such an intervention can be beneficial. This study was limited by the lack of attentional control; providing attention alone may positively affect the anxiety and depression of patients with cancer.

DOI Link: doi:10.1007/s10549-009-0425-y

The study evaluate the efficacy of sertraline for controlling hot flashes in women with or at high risk of breast cancer.

The study was organized by periods:

• Week 1: baseline
• Week 2: single-blind placebo run-in; those reporting hot flash score reductions of greater than 50% were then excluded.
• The remaining women received placebo or sertraline 25 mg/day and titrated weekly as needed to a maximum of 100 mg/day for weeks 3–6.

The study enrolled women aged 18 or older with personal or family history of carcinoma in situ or invasive breast cancer with reported hot flashes and a weekly hot flash score of greater than 15.

• N = 57 (randomized eligible) 
• N=53 (run-in phase)
• N=46 (assigned treatment)
• N = 41 completed treatment

Mean participant age was 55.8 years, and 95% had abreast cancer diagnosis.

Exclusion criteria included: progressive metastatic breast cancer, documented history of medication or treatment noncompliance, acute suicidal or homicidal ideation, any unstable clinically significant psychiatric condition including major depressive disorder, or concomitant use or use within 14 days of a monoamine oxidase inhibitor or another antidepressant drug, history of intolerable adverse reaction to sertraline, reduction of a weekly hot flash score by greater than 50% after placebo run-in.

A university cancer center hosted the study.

The study was randomized, double-blind, placebo-controlled.

Participants maintained a hot flash diary to record the number and severity of hot flashes per day.

Hot flash frequencies and scores suggested greater decline, but not statistically significant, in the sertraline-treated group compared with the placebo group.

The study was limited by its small sample size with reported insufficient statistical power to detect modest differences in hot flashes between groups. Study design did not take into account the possibility of pharmacokinetic interaction between sertraline and tamoxifen

DOI Link: doi: 10.1007/s00520-011-1345-z

To evaluate the efficacy aprepitant as an additional antiemetic among individuals who failed to obtain nausea and vomiting relief from 5-HT₃ antagonists and dexamethasone while receiving cisplatin-based chemotherapy

Physician and nurse investigators recorded patients' nausea and vomiting episodes daily while they were hospitalized. If discharged, patients their symptoms daily for up to 6 days.

• The study reported on 257 patients.
• Median age was 62 years with a range of 26–82.
• the sample was 70% male and 30% female.
• Cancer diagnoses were genitourinary (54.6%), gastrointestinal (20.2%), head and neck (13.2%), breast (3.9%), lung (3.5%), and other (6.6%).
• All patients had no prior exposure to cisplatin-based chemotherapy, and 97% of patients were chemotherapy naïve.

The study was conducted at a single inpatient site in Taiwan.

All patients were in active antitumor treatment.

This was a prospective, descriptive study.

• Vomiting was measured on a four-point scale of complete response, major response, minor response, or failure. 
• Nausea was measured on a four-point scale of none, mild, moderate, or severe.
• The acute phase was defined as day 1 of chemotherapy infusion, and the delayed phase was defined as days 2–6.

• In cycle 1, 19% of patients reported acute and delayed nausea and vomiting. 
• In cycle 2, 40 of 49 patients with CINV received aprepitant, and 98% experienced complete protection from acute vomiting, 93% from acute nausea, 65% from delayed vomiting, and 60% from delayed nausea.
• In cycle 3, 35 of 40 patients with CINV received aprepitant, and 100% experienced complete protection from acute vomiting, 100% from acute nausea, 77% from delayed vomiting, and 71% from delayed nausea.
• Adverse events associated with aprepitant for each cycle were hiccups (n = 5) and constipation (n = 4).

Aprepitant is an effective additional agent for CINV with minimal side effects; however, the medication should not routinely be used because only a small percentage of patients need an additional antiemetic.

• A risk of bias exists because no control group, blinding, or random assignment was used in this study. For example, while patients were hospitalized, the investigators collected their own data and, when patients were discharged, patients' providers were asking for the data.
• Key sample group differences could have influenced results.
• Measurement and methods were not well described, and measurement validity and reliability were questionable.
• Findings are not generalizable to other populations. The sample was primarily patients who were chemotherapy naïve, which may have influenced the overall rates of CINV.
• Although categories remained consistent for the measurement of nausea and vomiting, consistency in data collection (e.g., time of day), which may have influenced results, was not described. 
• Validity and reliability of the measurements was not described, and inter-rater evaluation was not performed to ensure consistency of measurement. 
• Delayed nausea and vomiting was defined as days 2–6 after chemotherapy, which is not typical timing for a delayed measurement.
• The generalizability of these findings is limited because it was a single institution study; furthermore, these findings are generalizable only to patients receiving cisplatin-based chemotherapy.
• Adverse events were reported in the results but the authors did not state how this information was obtained.

Nurses need to assess for CINV throughout chemotherapy and advocate for additional antiemetic therapy when needed. Aprepitant is an effective additional antiemetic medication for relief of CINV among patients receiving cisplatin-based chemotherapy.

DOI Link: doi: 10.1002/14651858.CD000978.pub5

To evaluate the evidence for prophylactic agents in management of oral mucositis in patients with cancer receiving treatment

Databases searched were MEDLINE, CANCERLIT, Embase, CINAHL, Latin American and Caribbean Health Sciences Literature (LILACS), System for Information on Grey Literature in Europe (SIGLE), and the Cochrane Database.

An extensive list of search terms and strategies used per database was provided in the article.

Studies were included in the review if they

• Were randomized controlled trials (RCTs).
• Compared an intervention to a placebo or no treatment.

A total of 383 references were retrieved. Risk of bias was evaluated according to the Cochrane Handbook for Systematic Reviews of Interventions. Studies were categorized as low, unclear, or high risk of bias. Studies were labeled using the GRADES system for evaluating quality of evidence.

• The final number of studies included in the review was 131.
• The total sample size across all studies was 10,514 with an across-study sample range of 12–301. 
• Studies involved a variety of cancers and patients receiving chemotherapy, radiation therapy, or both.

• Patients were in the active antitumor treatment phase of care.
• This study has clinical applicability to pediatrics.

• Only 8% of studies included were seen to have a low risk of bias. 
• Studies included a variety of treatments such as acyclovir, allopurinol rinse, aloe vera, amifostine, antibiotic paste, systemic antibiotics, axulene, benzydamine, beta carotene, chamomile, chewing gum, Chinese herbs, chlorhezidine, cryotherapy, epidermal growth factor, glutamine, granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), histamine gel, honey, hydrolytic enymes, indigo wood root, intestinal trefoil factor, keratinocyte growth factor, laser, anti-inflammatory drugs, oral care, pentoxifylline, pilocarpine, polymixin/tobramycin/amphotericin (PTA), traumeel, sucralfate, zinc sulphate, and povidone iodine. 
• From all analyses, at least moderately strong evidence of benefit was found for cryotherapy (RR = 0.74, 95% confidence interval [CI] 0.57–0.95, p = 0.02) for any mucositis and for keratinocyte growth factor (RR = 0.82, 95% CI 0.71–0.94, p = .0005) for any mucositis. 
• Weak and unreliable evidence for potential benefit was found with aloe vera, amifostine, glutamine, G-CSF, honey, laser, polymixin/tobramycin, amphotericin lozenges, and sucralfate.
• A substantial body of evidence showed no benefit of chlorhexidine.

Findings support the benefits of cryotherapy and keratinocyte growth factor. The low quality of evidence in most of the other interventions points to the need for ongoing, well-designed research in this area. The presentation of findings in many publications made meta-analysis impossible.

The rationale for the authors' summaries of findings was not entirely clear. Similar RR ratio results with similar evidence quality levels were identified differently in terms of potential benefit. Although the review was inclusive and extensive, interpretation of results was inconsistent. High heterogeneity existed in most interventions, and most studies were either at high or unclear risk of bias with low GRADES scoring. Studies did not always differentiate between mucositis and candidiasis, which would affect recommendations.

This article suggests strong support for use of cryotherapy and keratinocyte growth factor for mucositis prevention. It suggests possible benefit from aloe vera, amifostine, IV glutamine, G-CSF, honey, laser, and antibiotic lozenges. Sucralfate may reduce the severity of mucositis. These findings should be interpreted with caution, given the relatively low quality of overall evidence and high heterogeneity across studies included in meta-analysis, as well as the fact that treatments and sample characteristics were highly varied.

Database searched were Cochrane Oral Health Group's Trial Register, CENTRAL, MEDLINE, and EMBASE. Reference lists from relevant articles were searched, and the authors of eligible trials were contacted to identify trials and obtain additional information. Most recent search was conducted in August 2003.

A total of 25 randomized, controlled trials comparing agents prescribed to treat oral mucositis were evaluated.

• A total of 1,292 patients were involved in the 25 studies.
• All patients were receiving chemotherapy, radiotherapy, or both.

In one trial of 44 patients, a mouthwash of 300 mg allopurinol dissolved in water was compared to placebo. Patients rinsed with the mouthwash for one minute, four to six times per day. The study showed improvement but had a moderate risk of bias and weak evidence.

In another study of 80 patients with head and neck cancer and radiation-induced mucositis, patients were given immunoglobulin (10 mL on day 0, 5 mL on day 2, 5 mL on day 4) or placebo of 10% human albumin given at the same dosages and times. Both groups received nystatin. Patients who received immunoglobulin showed improvement; however, evidence was weak.

According to the authors, “There is weak and unreliable evidence that allopurinol mouthwash, vitamin E, immunoglobulin, or human placental extract improve or eradicate mucositis. There is no evidence that patient-controlled analgesia is better than the continuous infusion method for controlling pain; however, less opiate was used per hour, and duration of pain was shorter for patient-controlled analgesia. Further, well-designed, placebo-controlled trials assessing the effectiveness of allopurinol mouthwash, immunoglobulin, human placental extract, other interventions investigated in this review and new interventions for treating mucositis are needed.”

DOI Link: doi: 10.1046/j.1365-2648.2003.02936.x

DATABASES USED: CINAHL and MEDLINE

KEYWORDS: Cancer pain, pain management, and morphine; reference list from search articles 1990–2000

INCLUSION CRITERIA: Only articles using strong opioids (e.g., morphine, methadone, ketamine, fentanyl)

COMMENTS ON LITERATURE USED: Most articles were anecdotal or case studies. A total of 16 articles fit inclusion criteria.

FINAL NUMBER STUDIES INCLUDED = 16

KEY SAMPLE CHARACTERISTICS: Patients with cancer using strong opioids; no true sampling

The evidence does show encouraging results with use of fentanyl, methadone, and ketamine. Transdermal fentanyl is recommended for those with stable pain because it is difficult to titrate quickly. All of these strong opioids were well tolerated and seemed to be comparable to morphine.

Most of the evidence available is anecdotal.

More research is needed in this area.

To study treatment effect of lumbar sympathetic ganglion block (LSGB) on patients with lymphedema secondary to gynecologic cancer treatment who did not respond to conservative treatment, defined as complex decongestive physiotherapy or manual lymphatic drainage, compression therapy, exercise, and skin care.

Fluoroscopy-guided LSGB was performed on stage II lower limb lymphedema patients three times at two-week intervals. Thigh and calf measurements were measured upright at first visit and two weeks post-LSGB.

• N = 18 
• AGE RANGE = 32–79 years
• MALES: 0%, FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: 12 participants with stage II lower leg lymphedema; four participants with endometrial cancer; two participants with ovarian cancer
• OTHER KEY SAMPLE CHARACTERISTICS: All participants underwent radiotherapy, and 17 underwent bilateral pelvic lymph node dissections.

• SITE:  Single site 
• SETTING TYPE:  Outpatient 
• LOCATION: Gynecologic oncology pain clinic at an academic outpatient center

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

• Prospective clinical study

• Thigh and calf circumference
• Pain and satisfaction

Thigh and calf circumference reductions were greatest after the third LSGB and totaled 4 cm in thigh and 2 cm in calf. Pain score was also reduced.

This was a very small study measuring an intervention with radiation exposure, and procedure risks appeared to outweigh benefit. No long-term follow-up was noted. The study lacked researcher reliability and validity, with no noted description of thigh and calf measurement tools.

• Small sample (< 30)
• 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)
• Risk of bias (sample characteristics)
• Key sample group differences that could influence results
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Intervention expensive, impractical, or training needs

Careful consideration of risk to benefit ratio for patients undergoing LSGB is recommended because this procedure should only be performed under the auspices of research. High-quality controlled research studies with long-term follow-up are needed.