To evaluate the impact of melatonin on survivors of breast cancer with data analysis of secondary quality-of-life outcomes (sleep, mood, hot flashes)

Participants were randomized using 1:1 randomization format and received four months of 3 mg melatonin or placebo nightly at 9 pm.

• N = 85
• MEAN AGE: 59 years
• RANGE: 38-81 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Stage I-III primary nonmetastatic breast cancer, ductal carcinoma in situ, lobular carcinoma in situ, completed with active treatment (surgery, radiation, chemotherapy, and hormonal therapy) 60 days prior to enrollment.
• OTHER KEY SAMPLE CHARACTERISTICS: There was no history of other cancers except nonmelanoma skin cancer; no night-shift work; no active seizures with medication; and no beta-blocker, warfarin, hormonal therapy, black cohosh, flaxseed, soy, or sleep-aid use. There was also no melatonin use 30 days prior to enrollment.

• SITE: Single site
• SETTING TYPE: Outpatient
• LOCATION: Dana-Farber/Harvard Cancer Center, Boston, MA

PHASE OF CARE: Transition phase after active treatment

• Secondary analysis of the effect of melatonin on sleep, mood, and hot flashes
• Original study was a double-blind, placebo-controlled, randomized trial

• Subjective measures included Pittsburgh Sleep Quality Index (PSQI) (19-item scale)
• Center for Epidemiologic Studies Depression (CES-D) (20-item scale)
• North Center Cancer Treatment Group hot flash diary (frequency and intensity of hot flashes over seven days, and severity [1 = mild to 4 = very severe]).
• Diary data summed but number of and severity of hot flashes per day, calculation of hot flash score using frequency and severity

No baseline differences in characteristics were noted between groups (n = 48 melatonin; n = 46 placebo). Sleep outcomes included significant improvement in sleep quality, daytime dysfunction, and PSQI total scores in treatment versus placebo. Overall change of sleep over time using all time points, which was adjusted for multiple comparisons, showed overall high PSQI global scores in placebo group (1.67) (95% CI [0.67, 2.66]), indicating worse sleep quality. CES-D scores did not change over time. Hot flash frequency decreased over time for both treatment groups. Only grade 1-2 toxicities were reported.

The use of oral 3 mg of melatonin showed minimal side effects with possible impact on the improvement of subjective sleep quality. There was no exclusion for prior sleep disorders, limiting understanding of MOA of melatonin and preexisting sleep disorders. Sleep was a secondary outcome of this study and needs larger RCT trials to verify results.

• Small sample (less than 100)
• Details of randomization process are missing.
• Melatonin dose is often started low and increased as needed; yet the rationale for a stable 3 mg dose of melatonin in this study is unclear
• Underpowered for evaluation of effect on hot flashes

Oral 3 mg melatonin is potentially a safe and effective treatment for sleep disturbances in survivors of breast cancer with baseline poor sleep quality. However, additional larger scale-studies in which sleep is the primary variable outcome are needed using objective and subjective measures of sleep.

To compare the rate of febrile neutropenia and neutropenia grade 4 among patients receiving pegfilgrastim on the same day of chemotherapy and after 24 hours of the chemotherapy administration

A retrospective, single-center, non-randomized, cohort study was conducted that includes the evaluation of the eligible patient’s chart selected via an institutional electronic device. Patients should be 18 years and older. They have conducted this study from May 2007 to January 2013. In this study, researchers reviewed the administration of 6 mg of pegfilgrastim in patients on the same day of chemotherapy (day 1) or on day 2 or beyond (up to day 8) of CHOP chemotherapy with or without rituximab every three weeks for a total of eight cycles. The researchers highlighted the potential risk factors contributing to febrile neutropenia. The febrile neutropenia criteria includes temperature of at least 38 C and ANC < 500cells/mm3. 

• N = 141  
• AGE = 18 years and older
• KEY DISEASE CHARACTERISTICS: Non-Hodgkin lymphoma

• SITE: Single site    
• SETTING TYPE: Outpatient    
• LOCATION: United states of America

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

Retrospective, non-randomized, cohort study was conducted that contains chart review through institution electronic records.

• Fisher exact test
• SPSS software

Patients who received pegfilgrastim on the same day of chemotherapy had the highest incidence of febrile neutropenia (9.4%) compared to those who received the drug on day 1 or beyond (5.1%), showing a significant difference among both groups. In addition, the highest rate of dose reduction scenario was found in the day 1 group as compared to the day 2 and beyond  group (51.7% versus 40%). On the contrary, hospital stay duration and ICU admissions were high in the day 2 or beyond group versus the day 1 group (four admissions versus one admission).

The incidences of febrile neutropenia was less among the day 2 or beyond group of R-CHOP or CHOP.

• Baseline sample/group differences of import
• Key sample group differences that could influence results
• Measurement validity/reliability questionable 
• Findings not generalizable
• Time and duration of grade 4 neutropenia was not cleared, chemotherapy regimens were not standardized, and doses and cycles also differed.
• The type of infection was not clarified.

Additional studies need to be conducted for more accurate and reliable results.

To compare two oral care protocols with children receiving chemotherapy using either benzydamine or chlorhexidine oral rinses

Patients used each mouthwash for three weeks and then crossed over. Patients also used a standard mouthcare protocol consisting of toothbrushing using the Bass method and mouth rinsing with either of the allocated rinses in the early morning and at bedtime, normal saline rinsing within 30 minutes of meals, and normal saline rinsing every 4 hours in the first and third week and every 2 hours in the second week after chemotherapy. Patients were instructed in using a ballooning and sucking motion of the cheeks for 30 seconds without swallowing. Researchers provided reinforcement practice sessions every week and a cartoon reminder.

• The study reported on 40 patients.
• Patients had a median age of 10.3 years with a range of 6–17 years.
• Patients had solid and hematologic tumors.

The study was conducted from April 2000 to April 2001.

This was a prospective randomized, non-blinded, two-period crossover study with continual sequential analysis.

• Patient diaries were used. Researchers checked the remainder of rinse weekly to assess compliance.
• Parents and children were interviewed at each assessment about oral performance. The nurse or investigator assessed patients two times per week.
• Eilers' Oral Assessment Guide (OAG) was used with minor modifications. Interrelater reliability was established.

• A total of 34 participants completed the two protocols.
• No significant differences were found in patients' mean area under the curve (AUC) or oral mucositis according to order of protocols (t = 1.31, p > 0.05). No carry-over effect was found from initial oral care protocol.
• Fewer patients receiving chlorhexidin developed ulcerative lesions (27% versus 59%).
• A statistically significant reduction in ulcerative lesions was found using AUC (p < 0.05) and severity of mucositis (p < 0.05) in children on the chlorhexidine protocol.

This study did not demonstrate the superiority of the oral rinses over oral care.

• The study used a crossover methodology for control.
• The sample size was small.
• The study was not blinded.
• The study involved a wide age range.
• Patients were receiving a variety of chemotherapy protocols.
• Patients continued systematic oral care along with the protocol.
• Results may not apply to adult populations.

The study was conducted over an eight-month period. The first four months were with the control group, which received routine care, no oral protocol, and the center's standard use of 0.9% sodium chloride (NaCl) and benzydamine hydrochloride rinse to control oral mucositis (OM) when it developed.

The last four months involved the experimental group, which received an oral care protocol consisting of patient education, maintenance of patient diaries, and rinsing with normal saline chlorhexidine every two hours on days 1–21. The oral protocol prescribed toothbrushing; NaCl solution rinse for gums, tongue, and soft tissue; and chlorhexidine rinse every morning and evening, as well as NaCl rinse after each meal and every two hours for the second week only.

• The study reported on 42 children (21 in the control group and 21 in the experimental group) with hemotological or solid malignancies.
• Mean age was 10.3 years and a range of 6–18 years.

This was a prospective, comparative study.

• Oral assessment was performed initially and two times per week in each group.
• The Eilers Oral Assessment Guide was used.
• The Faces Pain Scale was used.
• Patients were observed for fevers and neutropenia.

• The oral protocol group experienced a 38% reduction of OM.
• Severity of OM (p = 0.000002) and related pain (p = 0.0001) were significantly reduced in the intervention group.
• The mean neutrophil count varied significantly between the seven time point evaluations (p = 0.008). A moderate negative correlation was found between the presence of OM and neutrophil count of the control group (p = 0.46) and protocol group (p = 0.15). Intensity of OM pain was significantly correlated with score of OM in two groups (p = 0.007).

• Assessment was performed twice per week.
• The results may not be generalizable to adult patients.
• The sample size was smal.
• A variety of chemotherapy protocols were used.
• The experimental group may have experienced a study effect.
• Use of chlorhexidine recommendation is in conflict with Multinational Association of Supportive Care in Cancer (MASCC) recommendations.

Although the sample is small, the evidence supports the use of normal saline found in other studies.

STUDY PURPOSE: To evaluate the evidence related to the efficacy of pyridoxine (vitamin B6) in preventing hand-foot syndrome (HFS) caused by anti-cancer therapies

TYPE OF STUDY: Systematic review

PHASE OF CARE:  Active antitumor treatment
 
APPLICATIONS: Elder care

• Incidence of HFS: No statistically significant differences were found in the risk of HFS among patients receiving placebo compared to pyridoxine (RR 0.96; 95% CI, 0.86–1.06; n = 551).  
• Incidence of grade 2 or worse HFS: No statistically significant differences were found in the risk of grade 2–4 HFS among patients receiving a placebo compared to pyridoxine (RR 0.96; 95% CI, 0.73–1.24; n = 551). In regard to different doses of pyridoxine, significant differences were found for prevention of grade 2 or grade 3 HFS with pyridoxine 400 mg PO daily compared to 200 mg PO. (RR 0.55; 95% CI, 0.33–0.92; n = 56).  
• Time to development of grade 2 or worse HFS: The median time for development of grade 2 or worse HFS was reported in one trial. Although the pyridoxine 400 mg group (87 days) was slightly longer than the 200 mg group (61 days), no statistical significant difference was found (p = 0.44).  
• Quality of life (QOL): In 2 RCTs (n = 106 and n = 34), there were no significant differences in QOL between the pyridoxine group and the placebo groups.  

Based on the analysis of results of five randomized controlled trials, there is not sufficient evidence to make any recommendation for patients taking pyridoxine to prevent HFS caused by chemotherapy drugs. However, that data suggests that pyridoxine 400 mg was more effective in preventing grade 2 and grade 3 HFS than pyridoxine 200 mg. Future research studies that include large sample sizes are needed to continue to evaluate pyridoxine’s efficacy and safety, especially high doses of pyridoxine, in comparison with placebo.

• Information from primary studies was not sufficient to perform subgroup analysis by types of chemo regimen.  
• This review included only RCTs.  
• Adverse effects of pyridoxine were not assessed absolutely.

HFS is a relatively common skin toxic reaction to certain chemotherapy. Nurses may collaborate with physicians in identifying effective treatments. Although RCT results do not support using pyridoxine for preventing HFS caused by chemotherapy, pyridoxine 400 mg PO may have some efficacy in preventing grade 2 and 3 HFS.

To evaluate the analgesic effect of electroacupuncture on pancreatic cancer pain

Patients were treated in a comfortable prone position. Disposable stainless steel filiform needles (40 mm in length and 0.3 mm in diameter) were inserted perpendicularly into the Jiaji points from T8 to T12 bilaterally to a depth of 25 mm. After de-qi sensation was achieved, the handles of the needles were respectively connected to a Han's acupoint nerve stimulator (HANS) at a frequency of 2/100 Hz and a current of 1 mA with a disperse-dense waveform. The needles remained in place for 30 minutes. The treatment was given once a day for three days. Sham acupuncture needles were used as a placebo and were put into the same points in the treatment group without inserting into the skin. The needles were then connected to the electric stimulator but with zero frequency and electric current. All patients were to maintain the same analgesic drug treatment.

• N = 60  
• AGE RANGE = 18–75 years
• MALES: 63.3% treatment arm (66.7% control arm), FEMALES: 36.7% treatment arm (33.3% control arm)
• KEY DISEASE CHARACTERISTICS: Histologically confirmed advanced pancreatic cancer at stages III–IV in the staging system of the Union for International Cancer Control
• OTHER KEY SAMPLE CHARACTERISTICS: Pain intensity of 3–6 on numeric rating scale (0–10), stable dose of analgesics at least 72 hours before randomization, estimated survival time greater than one month, never been treated by acupuncture, no other causes of pain (e.g., rheumatoid arthritis, disc disease), no contraindications for acupuncture (e.g., bleeding risk, infectious dermatosis, ulcer or scar at acupuncture points) or history of cerebrovascular accident (CVA) or spinal cord injury, study completed before treatment for pancreatic cancer

• SITE: Single-site    
• SETTING TYPE: Not specified    
• LOCATION: Fudan University Shanghai Cancer Center (FUSCC)

• PHASE OF CARE: Mutliple phases of care
• APPLICATIONS: Palliative care 

Pain intensity as assessed using a numeric rating scale of 0–10 after subjects were given an explanation of the rating scale. Ratings were done before treatment, after one to three treatments, and at one and two days after the completion of the treatments.

• Numeric rating scale from 0–10
• Analgesic record
• Adverse events

Pain intensity decreased compared with baseline after each of the three treatments in the acupuncture group. There was little change in the level of pain in the control group. The difference between the treatment arm and the control arm was statistically significant after each of the three treatments. Follow-up during the two days after treatment also showed a significant reduction in pain intensity in the treatment arm compared to the control arm. No infections at the treated points were noted during the trial, and there were no adverse events.

Pain intensity significantly decreased compared to baseline in the electroacupuncture group, a result that was significantly different than the result for those in the control arm of the study. There was no significant difference in the level of pain at any of the time points for those in the control arm of the study.

• Small sample (< 100)
• Risk of bias (no blinding)
• Findings not generalizable
• Other limitations/explanation: The study only included mild to moderate levels of pain. Pain was only assessed for two days after the treatment.

Pain is a significant problem for individuals diagnosed with pancreatic cancer. Standard treatment options include opioids, radiotherapy, and celiac plexus neurolysis; however, these are not always effective and may be limited due to their side effects. Nurses need to be aware of potential pain management options for patients with pancreatic cancer-associated pain in order to improve the patients' quality of life.

To assess the value of pharmacist-led teams as a model for improving drug delivery and implementing the role of the clinical pharmacist in direct patient care using cancer pain management as a focus area

Clinical guidance teams included clinical pharmacists, nurses registered in oncology, oncologists, and administrators. Pharmacists had at least two years' residency in the oncology department and underwent training in opioid pharmacotherapeutics, National Comprehensive Cancer Network guidelines, and Chinese practice guidelines, and they had to pass an examination. The pharmacist was responsible for patient and physician education, consulting in complex cases, and monitoring for drug efficacy and side effects. Patients with a history of cancer-related pain were enrolled. Patients were assigned consecutively to the intervention group, in which the guidance team was involved, or the control group, in which no guidance from the cancer pain therapy team was given. Outcomes were evaluated after six months. Patients in the experimental group had follow-up appointments via face to face or telephonic interviews twice a month. Study data were obtained from medical records and follow-ups.

• N = 542  
• AGE = 63.7% aged greater than 60 years
• MALES: 49.3%, FEMALES: 50.7%
• KEY DISEASE CHARACTERISTICS: Disease types were not provided.

• SITE: Multi-site  
• SETTING TYPE: Inpatient    
• LOCATION: China

Cohort design

• Numeric or visual scale for pain (mean value from follow-up scores used in analysis)
• Documentation of adverse effects (yes/no evaluation)
• Quality of life questionnaire (not described)

Compared to the control group, there were more frequent pain severity evaluations before opioid administration, more standardized dose titrations, more sustained-release formulations (p < 0.001), and fewer errors in dose conversion to other opioids (p = 0.017) in the experimental group. Pain scores were lower in the experimental group (p < 0.05), and the incidence of constipation, nausea, and vomiting was lower in the experimental group (p < 0.05).

The implementation of the clinical pharmacist role in guidance teams for cancer-related pain was associated with improvements in the process of medication management and pain scores.

The findings of this study suggested that the intervention of a multidisciplinary team to guide pain management can improve medication management, monitoring, and chronic pain outcomes.

To evaluate the effectiveness of a cryotherapy protocol in patients undergoing hematopoietic cell transplantation (HCT)

Medical records of patients undergoing autologous HCT for multiple myeloma were used to obtain data. All received high-dose melphalan as part of the conditioning regimen. Patients who were treated prior to the implementation of the cryotherapy protocol were compared to those who received cryotherapy in terms of the incidence, severity, and duration of mucositis. Data were collected to also compare the use of parenteral narcotics, use of parenteral nutrition, and hospital stay.

• N = 140
• MEAN AGE = 55 years
• MALES: 44%, FEMALES: 56%
• KEY DISEASE CHARACTERISTICS: All had multiple myeloma and received autologous HCT.

• SITE: Single site  
• SETTING TYPE: Inpatient  
• LOCATION: Canada

• PHASE OF CARE: Active antitumor treatment

• Retrospective cohort comparison

• World Health Organization (WHO) mucositis severity scale

Overall incidence of oral mucositis was 95.7% of those with no cryotherapy compared to 71.4% of those who received cryotherapy (p < 0.001). Median severity without cryotherapy was 2.5 compared to 2 with cryotherapy (p = 0.03). More patients without cryotherapy needed parenteral narcotics for pain control (p = 0.02), and duration of mucositis was about two days less with cryotherapy (p = 0.02). No differences existed in parenteral nutrition use or length of hospital stay.

The use of cryotherapy was associated with lower incidence, severity, and duration of mucositis among patients undergoing HCT receiving high-dose melphalan.

• Risk of bias (no blinding)
• Risk of bias (no random assignment)

Cryotherapy has been shown to be effective in reducing the severity of mucositis in patients receiving chemotherapeutic agents with a short half-life.

To introduce key points relating to lower abdominal flap transplantation with vascularized lymph nodes, and to evaluate the effects of breast restoration or reconstruction and lymphatic transplantation to treat upper-arm lymphedema after breast cancer surgery

Ten patients were recruited with postoperative, breast cancer-related lymphedema. Preoperatively, isotope radiography was used to determine lymphatic return obstruction. Patients were operated on in a standing position. A modified deep inferior epigastric perforator artery (DIEP) or microsurgical transverse abdominal myocutaneous island (TRAM) flap was accompanied by lymphatic tissue. The scar contracture of the axilla was relaxed and patients received abdominal transplantation of the lower abdominal flap with vascularized lymph node. Postoperatively, elastic bandages were applied for one year. Follow-up appointments occurred at one, three, six, and 12 months. The measurement indexes that were used included mid- and upper-arm circumference, clinical symptoms, and lymphoscintigraphy.

• N = 10  
• AGE RANGE = 36–50 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Breast cancer-related lymphedema
• OTHER KEY SAMPLE CHARACTERISTICS: All patients had lymphedema for three to five years.

• SETTING TYPE: Inpatient    
• LOCATION: Beijing, China

Controlled clinical trial

• Isotope radiography
• Multidetector-commuted tomography
• Mid- and upper-arm circumference measurement
• Clinical symptoms
• Lymphoscintigraphy

All of the flaps worked. One patient experienced delayed wound healing. There was no obvious improvement in lymphedema in one patient. Seven patients saw improvements in lymphedema clinical symptoms and mean limb perimeter. One patient recovered. The mean reduction was 2.122 cm (SD = 2.331). Limb volume decrease was statistically significant between preoperative and postoperative measures (p < .05).

Abdominal flap transplantation with vascularized lymph nodes and breast reconstruction, paired with treatment to upper-arm lymphedema and the use of elastic bandages as adjuvant treatment, is effective in restoring breast configuration and function.

• Small sample (< 30)
• Risk of bias (no control group)
• Other limitations/explanation: Inconsistent study results, lack of standardized surgical technique, and short follow-up.

This procedure may be effective for treating some women with breast cancer-related lymphedema, and it can guide future research on effective lymphedema therapy and postoperative monitoring.

To examine the effects of PG2 on fatigue in patients with advanced cancer.

PG2 was extracted from Astragalus membranaceus and is a polysaccharide mixture. It was reconstituted and dissolved in normal saline and mixed into 490 mL of normal saline for infusion. Patients were randomly assigned to the PG2 group or the placebo control group, which received infusions of 500 mL of normal saline. Patients received infusions three times a week for four weeks. After four weeks, all patients received open-label treatment with PG2 for another four weeks. Assessment of the outcomes was conducted at baseline and at the end of the first, second, and fourth week of each study cycle. A fatigue response rate was calculated as the percentage of patients who had at least a 10% improvement in fatigue scores at weeks 4 and 8.

• A total of 58 patients completed the full study; there were 84 patients for safety evaluation.
• Mean age was 60.5 years.
• About 39% of patients were men and 61.5% were women.
• Various tumor types were included, but  breast and head and neck cancers were the most common. Of the patients, 68% had metastatic disease.
• Average baseline Brief Fatigue Inventory (BFI) score was 6.04. 

The study was conducted at multiple settings in Taiwan.

Patients were undergoing the end of life and palliative phases of care.

This was a randomized, double-blind, placebo-controlled trial with an open-label extension.

• BFI, Taiwanese version
• Hematology blood tests

About 72% of the entered patients completed four weeks of the study, and 64.4% completed eight weeks. During the first week, PG2 administration resulted in a significantly greater fatigue response rate (PG2 = 57.14%; placebo = 32.3%; p = 0.043). By weeks 2 to 4, no significant differences were observed between the groups. About 82% of those who responded to PG2 reported a sustained benefit after the subsequent open-label use. For those who initially received placebo, after four weeks of open-label use, the fatigue response rate increased significantly after PG2 administration (57.14% response rate). Adverse events associated with PG2 were rashes (n = 3), eczema (n = 2), and pruritis (n = 2); none of these required medical treatment for resolution. White blood counts and differentials were similar between the groups.

PG2 had a positive effect on fatigue in patients with advanced cancer.

• The study had a small sample size, with less than 100 patients.
• Measurements/methods were not well described.
• Patient withdrawals were 10% or greater.
• The method of evaluating adverse events was not well described; the authors just stated that assessments were performed at each visit. 
• The study had a substantial drop-out rate. A few of these were from death with advanced disease; however, 4.4 % withdrew consent and 8.9% had protocol violations in the first cycle.

PG2 appeared to have potential benefit in reducing fatigue among patients with advanced cancer and may provide effective palliation of this symptom. Additional research is warranted to further evaluate efficacy and adverse events.