To determine the effectiveness of an oral management program in reducing oral mucositis (OM) incidence and severity in patients undergoing stem cell transplant (SCT)

Patients undergoing hematopoietic SCT were retrospectively enrolled in a study to determine if the occurrence and severity of OM was significantly different between a group of patients who received appropriate oral management and those who did not. The control group underwent SCT in 2007–2008, and the oral management group in 2009. This study included an oral evaluation, from the same oral health professionals, for all 48 enrollees prior to SCT. All serious dental issues (e.g., periodontitis, tooth extraction) were treated prior to starting SCT. Patients in the oral management group received oral care instruction with the transplant team prior to SCT. They also received an additional oral exam from the dentist and hygienist as well as instructions (including tooth brushing and oral swab use), based on their OM status. Both groups were treated with the same medications, based on the same OM toxicity scale, as graded by trained SCT nurses. OM in both groups was treated with azulene sodium sulfate and 4% lidocaine rinse.

• The study reported on 48 patients with cancer.
• The age range of the sample was 16–66 years.
• The sample was 48% male and 52% female.
• Cancer diagnoses included malignant lymphoma, acute myelogenous leukemia, acute lymphocytic leukemia, myleodysplastic syndrome, and multiple myeloma.
• Most of the patients had received allogeneic transplant (n = 35). 
• Significantly more patients in the OM group received allogeneic HCT.
• Ifosfamide, carboplatin, and etoposide (ICE) and fludarabine + melphalan/total body irradiation (TBI) conditioning regimens were significantly different between the oral management and control groups.  

This was a single-site inpatient study conducted at the Tsukuba University Hospital in Tsukuba, Japan.

Patients were undergoing the active antitumor treatment phase of care.

This was an observational, two-group trial.

OM was graded using the National Cancer Institute's (NCI’s) Common Terminology Criteria for Adverse Events (CTCAE, version 3.0).

• The incidence of any grade OM was significantly lower in the oral management group (p < 0.05).
• The median of the most severe OM score was 2 for the control group and 1 for the oral management group. This difference was statistically significant (p < 0.05).
• No significant difference was found between the groups in the duration of oral pain; however, the oral management group showed a tendency toward a shorter duration of pain (p < 0.1).
• All patients with sepsis, in both groups, recovered with antibiotics. No significant difference was found in the incidence of sepsis or in the amount of pain medication required.

Oral management was associated with lower incidence of OM and lower average severity of mucositis in patients undergoing HCT.

• The sample size was small with fewer than 100 patients.
• Important differences existed at baseline between groups, including the prevalence of allogeneic HCT. Key differences could have influenced results.
• A risk of bias exists because of the lack of a control group, blinding, and random assigment, as well as the sample characteristics.
• The study is further limited by the specific treatment group tested and the fact that it was a retroactive study .
• The investigators did not describe specific ongoing oral self care and if this differed between groups. Additionally, patient adherence to daily oral care was not evaluated.

With this study’s evidence, nurses can educate patients and reinforce continued oral care at home as well as recommend dental evaluation prior to starting chemotherapy for patients with oral health issues. These measures should help to reduce oral side effects and reassure patients that they have some control over disease management.

To investigate the effects of oral minocycline and topical steroid along with skin moisturizer on the incidence of skin effects in patients receiving panitumumab

Data were obtained from a retrospective chart review to compare the outcomes of patients who received prophylactic versus reactive oral minocycline. Patients received either 100 mg minocycline daily preemptively or as treatment for skin disorders. Topical steroid could be administered at any time based on physician discretion. All patients were to perform skin care by using a moisturizer.

• N = 38
• MEAN AGE = 62.5 years
• AGE RANGE = 35–87 years
• MALES: 65%, FEMALES: 35%
• KEY DISEASE CHARACTERISTICS: Patients with colorectal cancer. Most in the reactive treatment group were receiving panitumumab alone, and most in the prophylactic group were receiving panitumumab and FOLFOX6.

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

PHASE OF CARE: Active antitumor treatment

• Retrospective cohort comparison

• Common Terminology Criteria for Adverse Events (CTCAE), version 3

The incidence of grade 2 or higher acneiform rash was 44% in the prophylaxis group versus 84.6% in the reactive treatment group (odds ratio = 0.143, p = 0.04). No significant differences existed in incidence of other adverse reactions, including dry skin, pruritus, and paronychia. Incidence of grade 1 skin reactions was higher in the group that received prophylactic minocycline (p = 0.02). No significant differences in tumor response or time to treatment failure were observed.

The findings suggest that the prophylactic use of minocycline in patients receiving panitumumab may be helpful to reduce the incidence of more severe skin reactions.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Unintended interventions or applicable interventions not described that would influence results
• The use of topical steroids was at the investigator's discretion. The full components of general skin care were not described.

Prophylactic administration of tetracyclines may have some preventive effects in terms of skin toxicities with epidermal growth factor receptor inhibitiors; however, limited evidence exists to demonstrate efficacy. This small study provides limited evidence regarding this. Further well designed studies are needed to identify the efficacy of oral antibiotics and other aspects of skin care that are most beneficial to prevent skin effects from cancer treatment.

The purpose of the study was to evaluate the clinical efficacy of G-CSF and cost of daily versus every other day G-CSF for preventing and reducing duration of febrile neutropenia.

After treatment with the first course of R-CHOP, 100 mcg per person, G-CSF subcutaneously was begun when the white blood cell counts (WBC) were less than 1.5x10⁹/L and/or neutrophil counts were less than 0.5 x 10⁹/L. Patients were randomly assigned to receive G-CSF daily or every other day. Treatment was stopped when WBC recovered to greater than 5 x 10⁹/L. Total dosages and duration of G-CSF and any subsequent antibiotics were used for cost calculations

• 30 participants
• Mean age was 66 years, with a range = 24–80
• 53.3% were male; 46.7% were female
• All had diffuse large B-cell non-Hodgkin lymphoma and were receiving R-CHOP chemotherapy.  There was no bone marrow involvement
• All had ECOG performance status of 0–3.  Baseline WBC counts were similar in both groups
   

Single site

Active antitumor treatment

 Randomized, controlled trial

Recovery of WBC as defined required 4.0 ±1.4 days and 4.0±1.3 days in those receiving daily and every other day G-CSF respectively. Neutrophil count recovered in 3.4±1.1 days for those receiving daily treatment and in 3.6±1.4 days in those given G-CSF every other day. In the daily use group, three patients developed febrile neutropenia, and two patients in the every other day group developed febrile neutropenia. The same number of patients in each group who were given prophylactic antibiotics developed febrile neutropenia. Cost of treatment in those receiving daily G-CSF was significantly higher than cost in the every other day group (p < 0.0001).

There was no clinical difference in WBC and neutrophil recovery time between patients who were given daily or every other day G-CSF during a course of R-CHOP chemotherapy

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Limited study duration and duration of follow-up

Findings suggest that less frequent G-CSF administration may be as effective as daily administration to facilitate WBC and neutrophil recovery. Further larger scale research in this area is warranted.  If this approach is further supported, it can provide less costly care to achieve desired results.
 

To evaluate the efficacy of aprepitant in the prevention of chemotherapy-induced nausea and vomiting (CINV) and hypersensitivity reactions in patients with gynecologic cancer who are receiving paclitaxel and carboplatin

All patients received either 1 mg of granisetron or 4 mg of ondansetron and 20 mg of dexamethasone IV on day 1. Patients in the placebo group received a placebo on days 1–3, and patients in the aprepitant group received 125 mg of aprepitant PO on day 1 and 80 mg of aprepitant PO on days 2 and 3.

• N = 297   
• MEAN AGE = 59 years
• AGE RANGE = 24–79 years
• FEMALES: 100%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Ovarian cancer, endometrial cancer, cervical cancer, peritoneal cancer, tubal cancer

• SITE: Multi-site   
• SETTING TYPE: Not specified    
• LOCATION: Japan

PHASE OF CARE: Active antitumor treatment

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

Hypersensitivity reactions were graded using the Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0. From days 1–5, patients recorded the highest level of nausea severity each day (absent, mild, moderate, severe), number of episodes of emesis, and time of each episode. Patients also recorded the date and time of each rescue antiemetic and responses to questions about appetite. Adverse effects were graded using CTCAE, version 4.0.

The rates of hypersensitivity reactions were similar in the control and test groups. Patients who received aprepitant, when compared to the control group, had higher rates of no vomiting in the overall phase and during the acute and delayed phases (p < 0.0001, p < 0.0001, p = 0.0495). The rate of \"no significant nausea\" was also significantly higher in the aprepitant group in the overall phase and delayed phase (p = 0.0143, p = 0.0274). Complete response (no vomiting and no rescue medication) was significantly higher in the aprepitant group in the overall and delayed phases (p = 0.0073, p = 0.0072).

Aprepitant is beneficial when used in combination with a 5-HT₃ receptor antagonist and dexamethasone in patients with gynecologic cancer receiving paclitaxel and carboplatin.

Aprepitant may be given as CINV prophylaxis for patients receiving paclitaxel and carboplatin for the treatment of gynecologic cancer.

Patients were randomized to a yoga plus exercise group or an exercise alone group. Both groups did aerobic exercises three days per week for six weeks. The yoga program involved postures, meditation, and relaxation with imagery. Yoga was provided in 60-minute group sessions three days per week on the same day as exercise was done. Yoga was supervised by a certified therapist.

• N = 40  
• MEAN AGE = 48.6 years
• MALES: Not written, but it seems to be 0%, FEMALES: Not written, but it seems to be 100%
• KEY DISEASE CHARACTERISTICS: Patients with unilateral breast cancer who were mentally intact and whose cancer treatment was completed at least three years prior
• OTHER KEY SAMPLE CHARACTERISTICS: A cardiologist performed the cardiologic examinations. Exclusion criteria included chronic systemic disease and metastasis, relative and absolute contraindications for exercise training, drug therapy with a risk for exercise, types I and II diabetes mellitus, uncontrolled hypertension, and cardiac disease.

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

• PHASE OF CARE: Late effects and survivorship

Randomized, controlled trial

• European Organisation for Research and Treatment of Cancer Quality of Life Questionnarie (EORTC C30)
• Fatigue Severity Scale (FSS)
• Six-minute walk test
• Dynamometer for peripheral muscle strength
• Borg Fatigue Scale (BFS)
• Borg Dyspnea Scale (BDS)

• Dyspnea, fatigue, and leg fatigue perception were significantly decreased in both groups, and the improvement was similar in the two groups (P < 0.05).
• Peripheral muscle strength assessments improved in both groups (P < 0.05).
• Quality of life assessments improved in both groups (P < 0.05).
• Well-being, role function, and emotional and social functioning were statistically better in the group that included yoga compared with the aerobic exercise group (P < 0.05).
• FSS scores decreased more in the yoga and aerobic exercise groups compared to the group that received aerobic exercise alone (P < 0.05).

Aerobic exercise training and yoga improved functional capacity and QOL and reduced fatigue in patients with breast cancer. The addition of yoga to aerobic exercise was associated with greater improvements in fatigue perception and QOL measures.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Other limitations/explanation: There were several limitations in this study. A group that practiced yoga alone was not included, therefore the effects of yoga alone could not be reported. The exercise training period was six weeks. Longer exercise interventions are needed to determine their effects on other outcomes. The power analysis was performed post-hoc according to the primary outcome (6MWT) but revealed that the study had sufficient power (85%) to support our conclusions. Yoga was provided in a group setting, and there was no similar group activity in the exercise alone group. Group support may be responsible for some of the differences seen in perceptions and overall QOL. Areas for future research include appropriate levels of intensity for exercise training, the application of the program during cancer treatment, and the application of the program with patients receiving bilateral mastectomies.

The findings of this study suggest that the addition of yoga to exercise interventions may cause improvements in perception of dyspnea and fatigue among breast cancer survivors that are greater than the effects of exercise alone. Mind–body approaches should be considered as adjuvant interventions for fatigue.

STUDY PURPOSE: To determine the prophylactic effects of honey on radiation- and chemotherapy-induced mucositis

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 7
• TOTAL PATIENTS INCLUDED IN REVIEW = 190 test groups, 191 control groups
• SAMPLE RANGE ACROSS STUDIES: 13–127
• KEY SAMPLE CHARACTERISTICS: In five studies, patient received radiation therapy (260 patients, two studies radiation therapy and chemotherapy [121]). Only three studies mentioned age range (13–89 years).

PHASE OF CARE: Active antitumor treatment

Honey treatment reduced the incidence of oral mucositis in the honey group by 65% compared to the control group. The type of radiation therapy (source, dose) may have influenced the results.

Mostly low quality/high risk of bias studies

Honey prevents the incidence of mucositis compared to no intervention. However, more randomized, controlled trials are needed to determine the prophylactic effects of honey on patients receiving radiation or radiation and chemotherapy.

STUDY PURPOSE: To identify all observational studies that examine the role of calcium and magnesium infusions in the chemoprevention of oxaliplatin-induced sensory neuropathy in gastrointestinal cancers

DATABASES USED: PubMed, EMBASE, Science Citation Index, Expanded Chinese National Knowledge Infrastructure

KEYWORDS: Calcium gluconate; digestive system neoplasms; magnesium sulfate; neurotoxicity syndrome; oxaliplatin; oxaliplatine; eloxatine; ACT 078 L-HP; neuropathy; chemotherapeutic agent; toxicity; calcium; Ca; Ca and magnesium; Mg or Mg and oesophageal cancer; gastric cancer; stomach cancer; bowel cancer; colorectal cancer; colon cancer; rectal cancer; pancreatic cancer; hepatocellular carcinoma; liver cancer; biliary tract cancer

INCLUSION CRITERIA: Studies for meta-analysis included randomized, controlled trials and cohort studies that involved calcium and magnesium infusions in chemoprevention of oxaliplatin-induced sensory neurotoxicity in gastrointestinal cancers.

EXCLUSION CRITERIA: Letters, case studies, reviews, comments, studies on cell lines, animal studies, and any study with no control group

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: National Cancer Institute Common Toxicity Criteria (NCI CTC) and oxaliplatin-specific scale (OSS) were used. Meta-analysis was done on six studies that had reported responses. A sensitivity analysis was used by repeating meta-analysis but excluding one study at a time. Odds ratio and its 95% confidence interval were calculated.

• FINAL NUMBER STUDIES INCLUDED = 16 (15 full manuscripts and one abstract)
• TOTAL PATIENTS INCLUDED IN REVIEW: 1,765
• KEY SAMPLE CHARACTERISTICS: The studies were randomized, controlled trials, prospective and retrospective, that included magnesium and calcium infusions for the prevention of chemotherapy-induced neuropathy in patients with gastrointestinal cancers. Patients had gastrointestinal, colorectal, hepatocellular, and small intestine cancers. Patients were aged 18–37 years.

• PHASE OF CARE: Survivorship
• APPLICATIONS: Pediatrics, elder care

The difference in the incidence of grade 1 oxaliplatin-induced neuropathy was statistically significant between those who received calcium and magnesium infusions and those who did not receive the treatment (NCI CTC: OR .44, 95% CI 0.31–0.62, p = 0.000; OSS: OR 0.30, 95% CI 0.20–0.45, p = 0.000). Similar results were found in the incidence of grade 2 oxaliplatin-induced neuropathy (NCI CTC: OR 0.60, 95% CI 0.46–0.77, p = 0.000; OSS: OR .45, 95% CI 0.30–0.67, p = 0.000). No difference was observed in grade 3 neuropathy in patients treated with calcium and magnesium infusions opposed to those who were not treated with calcium and magnesium infusions (NCI CTC: OR 0.67, 95% CI 0.44–1.01, p = 0.054; OSS: OR 0.66, 95% CI 0.34–1.29, p = 0.224). Overall, calcium and magnesium infusions reduced the incidence of peripheral neuropathy grades 1 and 2. This did not include the incidence of grade 3 neuropathy. The calcium and magnesium infusions did not lessen the treatment effects of oxaliplatin (OR 0.89, 95% CI 0.67–1.17, p = 0.391).

Most research in chemotherapy-induced peripheral neuropathy has focused on treatment-related side effects. Positive studies in this area are lacking. However, this analysis of six studies of calcium and magnesium infusions in the prevention of chemotherapy-induced peripheral neuropathy is promising. Large, randomized trials would need to be done to determine efficacy.

• More than likely, studies that had negative results were not published, so the authors concluded that bias could not be ruled out.
• The design of the studies varied greatly. The majority of the studies were retrospective or nonblinded observations.
• There may be a discrepancy in the results because the number of treatments, duration of treatments, cumulative doses of oxaliplatin, assessment scales, and timing of assessments varied.
• Given the small subgroup and that the analysis did not provide all of the information needed, care should be taken in interpreting the results and conclusions.

One of the limitations speaks to lack of consistency among various assessment scales for peripheral neuropathy. Whether a preventive study or treatment study, assessment is critical to patients with peripheral neuropathy. Nurses should be knowledgeable concerning various assessment scales and should use the scales from baseline through survivorship.

To establish the safety and efficacy of traditional Chinese herbal medicine for the treatment of fatigue in patients with cancer who do not have anemia

Patients were recruited from those who visited a herbal medicine clinic. Patients were given a combination of 12 herbs, which they slowly cooked in 150 ml of water. This decoction was taken twice daily for six weeks. Study measures were obtained at baseline and after six weeks. Patients were evaluated by a traditional Chinese medicine doctor at the beginning and end of the study.

• N = 33
• MEDIAN AGE = 60 years (range = 41–81 years)
• MALES: 42%, FEMALES: 58%
• KEY DISEASE CHARACTERISTICS: Varied tumor types; off treatment for at least one month
• OTHER KEY SAMPLE CHARACTERISTICS: All had moderate to severe fatigue defined as a score of at least 4 on a 0–10 point scale; hemoglobin of at least 10 g/dl

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

• PHASE OF CARE: Transition phase after active treatment

Open-label phase I–II

• Single fatigue item scale from the Chinese version of the MD Anderson Symptom Inventory (MDASI)

Fatigue levels declined during the study (p = 0.024), and 64% of patients said they felt better within two weeks, and 33% felt better after three weeks. No adverse events were reported.

The findings of this study suggest that that a traditional Chinese herbal medicine formulation appears to be safe and may be helpful in the treatment of depression among patients with cancer.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment) 
• Other limitations/explanation: The approach described for the evaluation of potential side effects was according to traditional Chinese medicine practice, and its general validity is not clear.

This study was limited by design and sample size, so no firm conclusions about the safety and efficacy of traditional Chinese herbal medicine can be made.

To summarize and evaluate the state of clinical research on the use of Chinese herbal medicine in the treatment of cancer-related pain

The type of article is systematic review.

Databases searched were Chinese Biomedical Literature, Chinese Medical Current Content, Wanfang, and Weipu databases in Chinese, and PubMed and EMBASE in English.

Search keywords were Chinese herb, Chinese medicine and neoplasms and pain. Specific search terms in English and Chinese are displayed in this report.

Studies were included in the review if they were reports of original work on cancer-related pain.

Reviews, commentary, abstracts, and reports on pain associated with cancer therapies were excluded.

An initial search provided 212 Chinese articles and 161 articles from English literature.

Study quality was evaluated using the National Cancer Institute’s Levels of Evidence for Human Studies of Cancer Complementary and Alternative Medicine guidelines.

• A final sample of 115 articles, 106 of which were retrieved from Chinese databases, was included in the report.
• Studies included 3,878 patients. Study sample sizes reported ranged from to 46 to 250 patients.

Results are organized according to route of administration: oral, IV, and other methods of application, such as inhalation.

Treatment Outcomes

External application: This is the most common use. This area included 41 studies

• Analgesic effect was equivalent to positive control treatment across studies.
• In numerous studies, the comparison positive control was nonsteroidal anti-inflammatory drugs (NSAIDs) or palliative chemotherapy or radiation therapy. Few studies were in comparison to opioids.

Oral administration: 48 studies were in this category. Comparison positive controls in this group tended to also be palliative chemotherapy or radiation therapy, NSAIDs, and opioids. Dosage ranges of comparison medications were not discussed.

IV infusions: 23 studies were reported; however, authors included studies of intramuscular administration, and samples being actively treated with chemotherapy or radiotherapy for pain. Overall positive results compared to placebo or no active controls were reported.

Other administration methods: One study involving inhalation and one involving per rectum administration are discussed. 

Adverse Reactions: Adverse events were slight and brief, and in most cases patients did not require further intervention. Adverse effects were reported to be higher in conventional medicine control groups.

The authors conclude that Chinese herbal medicine may be useful for managing cancer pain. However, there is no discussion of the fact that control comparisons used were no specific pain treatment, or low-level interventions such as NSAIDs. In this regard, controls used in the research summarized here were insufficient to provide realistic scientific comparisons. Methods of pain measurement reported here show mostly use of a single pain measure such as various verbal reporting scales, which can be expected to influence reliability and validity of individual study results. The authors point out that the quality of studies, design and methods, and study reporting was low. The authors suggest specific approaches in study design for improvement of research in this area.

Well-designed research in the use of Chinese herbal medicine is needed to enable firm conclusions about efficacy. Research regarding the role of this type of treatment as adjunctive pain management would also be useful. Findings here provide only minimal support for the use of Chinese herbal medicine to effectively manage cancer-related pain.

To investigate the efficacy and safety of transdermal fentanyl for mucositis pain caused by chemoradiotherapy in patients with esophageal squamous cell carcinoma

Forty-six patients with moderate to severe oral mucositis receiving chemoradiotherapy for esophageal squamous cell carcinoma were given transdermal fentanyl for pain management.

• N = 46
• MEAN AGE = 56.3 years (range = 42–72 years)
• Males: 32%, Females: 12%
• KEY DISEASE CHARACTERISTICS: Pain management with transdermal fentanyl for the patients who developed oral mucositis during chemoradiotherapy from October 2010 to December 2012
• OTHER KEY SAMPLE CHARACTERISTICS: Patients with painful mucositis had pain scores greater than or equal to 4 or oral mucositis grade more than 1.

• SITE: Single site
• LOCATION: Binzhou Medical University, China

• PHASE OF CARE: Transdermal fentanyl treatment

This was an unblinded, nonrandomized study.

Pain scores on a Numeric Rating Scale (NRS), the National Cancer Institute's Common Toxicity Criteria, administration frequency of transdermal fentanyl, and post-treatment adverse effects data were analyzed using SPSS. The paired sample Wilcoxon signed rank test was used to evaluate differences before and after treatment, quality of life, nutritional status, and oral hygiene.

The NRS pain scores were p < 0.0001 before and after treatment. Significant differences (p < 0.001) were observed between the indices of quality of life. 15.2% of patients reported nausea and vomiting, 13% developed dizziness, and 10.9% complained of gastric discomfort. All these symptoms were mild and disappeared after proper management.

In this study, transdermal fentanyl was effective in reducing pain from oral mucositis caused by chemoradiotherapy.

• The first study was performed in one center only.
• Sample size small
• Sample not randomized or controlled 
• Short-term observations included.
• Inconsistent administration of opioids

Nurses should be aware of the benefits of transdermal fentanyl but also should be aware of its side effects and half-life so they can educate and support patients in pain.