To summarize the literature on calcium phosphate oral rinse for the prevention and treatment of oral mucositis (OM)

• FINAL NUMBER STUDIES INCLUDED = 30
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,392, of which 890 patients received Caphosol
• SAMPLE RANGE ACROSS STUDIES: Across 19 studies of patients undergoing hematopoietic stem cell transplant, 5–154; across 11 studies of patients with head and neck cancers, 11–218
• KEY SAMPLE CHARACTERISTICS: Studies measured grade and duration of OM, pain assessment and medication, total parenteral nutrition, patient satisfaction, treatment compliance, oral infection rates, duration of hospitalization, polyethylene glycol use, and swallowing. Most of the studies were from single centers and involved free Caphosol provided to the hospital. Observational studies were included. The abstracts and conference proceedings did not consistently provide details about standard treatments and study design.  

• PHASE OF CARE: Active antitumor treatment
• CLINICAL APPLICABILITY: Pediatrics

Caphosol was found to reduce OM grade, duration, or both in 24 out of 30 studies. Caphosol was associated with a reduction in OM-associated pain in 14 of 17 studies with more than 30 patients and 6 studies with fewer than 30 subjects. Data regarding nutrition, patient compliance, and length of hospitalization were conflicting, but the majority demonstrated a benefit with Caphosol. Two studies reported potential cost savings with the use of Caphosol. Three studies with 30 patients and three single-center studies with controls of standard mouth care and MuGard^® did not find significant differences in OM grade or duration. Two studies of more than 30 patients did not demonstrate a benefit associated with OM-related pain. One study did not find a significant difference in nausea or dysphasia for Caphosol-treated patients. Three studies failed to demonstrate any differences in length of stay.

The majority of the studies included in the review reported some benefit from Caphosol use. The data demonstrate the opportunity to further study the role of supersaturated calcium phosphate oral rinse in the prevention and treatment of OM.

• The studies were heterogeneous in their design, so data could not be pooled or consolidated.  
• The review was funded by EUSA Pharma.  
• Porterhouse Medical Ltd provided medical writing services and was funded by EUSA Pharma.  
• Only two full-length, peer-reviewed articles were included in this review.  
• At least 12 of the 30 studies included in the review were observational or retrospective studies.  
• The definition of standard oral care was not well defined in all of the studies, so determining the role of Caphosol in the improvements documented is difficult.

The effects from OM remain a significant challenge for patients receiving cancer treatment. Nursing involvement in prospective, randomized, blinded studies could provide the best practice data needed to recommend treatments for OM. The limitations for the studies included in this review are significant and do not provide rigorous scientific support for the use of Caphosol.

To determine the effects of various opioids in treating cancer-related pain

• Databases searched were MEDLINE, EMBASE, the Cochrane Library, National Health Service Centre for Reviews and Dissemination, Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment (HTA), Turning Research into Practice (TRIP), and National Institute for Clinical Excellence (NICE).
• Authors did not include search keywords in the report.
• Studies were included if they
  • Were systematic reviews or randomized controlled trials whose results were published in any language.
  • Included more than 20 participants, of whom investigators followed up with 50%.
• Authors did not list exclusion criteria.

Investigators reviewed 34 studies. Investigators used 22 studies as the basis of their report. Investigators evaluated studies by performing a GRADE evaluation of the evidence, using the following criteria: type of evidence, quality, consistency (similarity of results across studies), directness (generalizability), and effect size. Evidence ratings were very low, low, moderate, and high.

• Authors did not specify total sample size.
• The sample included patients with cancer-related pain.

Authors reported results relative to pain, need for rescue analgesia, function, quality of life, patient preference, and adverse events.

Morphine is the standard opioid in the management of moderate to severe cancer pain. Evidence from this study was insufficient to allow authors to compare other opioids to it. Evidence from this study was insufficient to allow conclusions about codeine. Investigators categorized the effectiveness of dihydrocodeine, a newer option for pain control, as unknown. Evidence from this study was insufficient to allow authors to rate the effectiveness of transdermal fentanyl. Hydromorphone may be as effective as morphine or oxycodone and may cause fewer adverse effects. Methadone may be as effective as morphine or oxycodone, for reducing pain, and the two opioids' rates of associated adverse effects are similar. Oxycodone and morphine may be equally effective in reducing pain. Tramadol may be as effective as morphine, but morphine seems to have quicker onset.

Authors deemed all evidence cited in this review to be of very low or low quality.

To evaluate the effectiveness and safety of prucalopride, a 5-HT4 receptor agonist, in patients with chronic constipation.

Patients with self-reported chronic constipation for at least six months could enroll in the study. The 12-week study procedure comprised a two-week placebo run-in period to determine frequency of bowel movements (BMs). Patients with two or fewer spontaneous complete BMs per week were randomized to one of three treatment groups (2-mg prucalopride, 4-mg prucalopride, or placebo), with study medication taken once daily with breakfast for 10 weeks.

• The study reported on a sample of 641 patients.
• Mean patient age was 47.9 years (range 18–95).
• The sample comprised 555 women (87%) and 86 men (13%).
• Patients were aged older than 18 years and had a history of self-reported chronic constipation for six months or less that was not caused by drug use, surgery, or organic disorders of the large intestine.

• Multi-site
• United States

This was a randomized, double-blind, placebo-controlled, parallel-group phase III trial.

• Patient diary
• Patient global assessments
• Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire
• Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaire
• Medical Outcomes Study (MOS) 36-item Short-Form Health Survey (SF-36)

• Significantly more patients in the prucalopride 2-mg (23.9%) and 4-mg (23.5%) groups reported three or more spontaneous complete BMs per week compared with the placebo group (12.1%) over the 12-week study period (p ≤ 0.01).
• Significantly more patients in the prucalopride 2-mg (42.6%) and 4-mg (46.6%) groups reported an increase from baseline of at least one spontaneous complete BM per week compared with the placebo group (27.5%) over the 12-week study period (p ≤ 0.001).
• Patients in both prucalopride groups had an increased percentage of normal consistency BMs (p ≤ 0.05), had no straining (p ≤ 0.01), used significantly fewer laxatives per week (p ≤ 0.01), used fewer enemas per week (p ≤ 0.05), rated their treatment effectiveness better (p ≤ 0.001), and rated their constipation as less severe (p ≤ 0.001) compared with the placebo group.
• The most common adverse events were headache, nausea, abdominal pain, diarrhea, and flatulence.

Prucalopride 2-mg and 4-mg administration improved the frequency, consistency, and quality of defecation and led to complete bowel evacuation in adults with chronic constipation.

• Patients who had cancer or were receiving opioid therapy were excluded from the study.
• Eighty-seven percent of the participants were women.

Prucalopride (2 mg or 4 mg daily) appeared effective in the treatment of chronic constipation in adults. Research for applicability in patients with cancer is warranted.

A single dose of nebulized morphine-6-glucuronide (M6G) (the active metabolite of morphine) was given to patients with cancer who had breathlessness. Three dose levels were studied:  5, 10, and 20 mg of M6G. The single dose of morphine was inhaled using an Acorn Porta-Neb jet nebulizer over 15 minutes.

• The sample was comprised of nine patients. 
• No patient characteristics were reported other than age (median = 51 years; range 45–77).
• Six patients were already receiving morphine.

• Unknown
• Results were reported from St. Bartholomew Hospital in London, United Kingdom.

This was an open, uncontrolled study that randomized patients to one of three dose levels.

• 100-mm visual analog scale (VAS) and modified Borg scale were used to quantify breathlessness, anxiety, and effort of breathing at pretreatment and at 15, 30, and 60 minutes posttreatment.
• VAS and verbal rating scales were used to assess nausea, drowsiness, and other side effects.

All patients reported a subjective improvement in breathlessness by the VAS and the Borg scale. A significant difference (p = 0.023) in dyspnea VAS was observed with time across all time points. No significant difference existed among the three treatment groups across all time points (p = 0.176), suggesting no difference among the three doses. A significant difference in dyspnea was found between patients. No significant changes existed in anxiety VAS and effort of breathing VAS with time or with dose. Minimal adverse effects were noted.

Nebulized M6G was relatively safe and possibly therapeutic in patients with cancer-related breathlessness.

• A small number of patients were studied.
• The study was reported as a letter to the editor.

A randomized study is planned.

The study used a two-phase, multimodal, cognitive-behavioral therapy (CBT) combined strategy:  (a) over 3 to 10 weeks and (b) over eight weeks; eight weekly sessions lasted 90 minutes.

The purposes were to establish treatment objectives, stimulus control, sleep restriction, coping strategies for fatigue, and reframe maladaptive cognitions.

Outcomes were sleep, mood, fatigue, and global and cognitive quality of life (QOL).

• The sample was comprised of 10 women with nonmetastatic breast cancer (stages I–III).
• Mean age was 54.3 years.
• Women completed chemotherapy and/or radiation therapy.
• All had a diagnosis of chronic insomnia disorder per the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV).
• All had completed high school.

• Single site
• Patients were recruited from the community sleep laboratory and subjects’ homes.
• Quebec, Canada

Patients were undergoing the long-term follow-up phase of care.

The study used a prospective, nonrandomized, repeated measures, quasiexperimental, single-case design comparing each individual over time.

• Insomnia Interview Schedule (ISI) 
• Sleep diary
• Self-report scales
• Polysomnography and breathing parameters

Most women experienced a statistically significant improvement in sleep efficiency and decreased total wake time pre- and posttreatment. Sleep efficiency continued at the six-month follow-up, but total wake time did not. Findings on sleep diaries were corroborated by objective measures.

• The study had a small sample size.
• The sleep diaries were incomplete.
• The potential existed for influence factors, such as intragroup alliance and empathy.
• Sleep improvement may be an effect of time away from cancer therapy.
• A trained psychologist must administer the tests; in addition, cost is incurred by using a sleep laboratory for polysomnography.

Patients received multimodal cognitive-behavioral therapy (CBT) that combined cognitive, behavioral, and educational strategies. Treatment consisted of eight weekly sessions administered in a group of five participants combined with use of stimulus control, sleep restriction, cognitive therapy, sleep hygiene, and fatigue and stress management. The treatment protocol was based on clinical procedures developed by Morin (1993) and adapted by the investigators for the cancer population.

Ten breast cancer survivors participated in this pilot study. 

Patients were included in the study if they

• Completed radiotherapy of chemotherapy for a stage I to III breast cancer at least one month prior to enrollment
• Met the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) diagnostic criteria for a chronic insomnia syndrome.

Patients who regularly used psychotropic medications other than hypnotics were excluded unless the dosage use was stable in the last month and did not increase during the study.  Individuals currently receiving psychotherapy were also excluded.

• Cancer research facility
• Participants were recruited via fliers and pamphlets.

Patients were undergoing the long-term follow-up phase of care.  

This was a single-arm study with no control group.

Multidimensional Fatigue Inventory (MFI)

Nonparametric statistical testing revealed significant improvements in the general and physical subscales of the MFI; there was no significant change between pre- and posttreatment on the mental, activities, and motivation subscales of the MFI. There was no significant change observed from posttreatment through six-month follow-up on the MFI general and physical subscales, suggesting that the treatment gains were sustained over time.

• The study had a small sample size.
• The effect could have potentially occurred as a result of group support rather than the CBT intervention itself.
• Sustained improvements in fatigue may also be a result of a maturation effect wherein fatigue declined as might be expected, with greater distance from treatment.
• Trained personnel were needed to administer the CBT intervention.
• Group treatment had costs.

All patients received DLT divided into two phases. The intensive treatment phase was administered over a one to three-week time period (daily treatment for at least five consecutive days), and the maintenance phase mainly was carried out by the patient and his or her family members at home. Limb volume was measured on days 5, 12, 19, and 195.

• N = 219  
• MEAN AGE = 59.9 years (SD = 14.3 years)
• MALES: 10.1% (most were lower-extremity participants), FEMALES: 89.9% (most were following breast cancer treatment)
• KEY DISEASE CHARACTERISTICS: Patients with upper or lower extremity unilateral lymphedema
• OTHER KEY SAMPLE CHARACTERISTICS: Lymphedema was the primary reason for clinical treatment.

• SITE: Multi-site    
• SETTING TYPE: Outpatient    
• LOCATION: France

• PHASE OF CARE: Late effects and survivorship
• APPLICATIONS: Elder care 

Observational, prospective, longitudinal cohort study

• Demographic data
• Lymphedema volume was measured using the truncated cone formula.
• Excess limb volume was calculated using the formula (LLV – HLV)/HLV x 100.

Initial intensive lymphedema treatment resulted in a 31% volume reduction, but the benefits were somewhat abolished when volume increased by 16.5% during the six-month maintenance phase. The only independent variable predictive of volume reduction after intensive therapy was the presence of previous intensive DLT. The most frequent adverse events were skin redness (18.4% of patients) and compression marks (42.3% of patients). Blisters requiring that treatment be stopped were uncommon (1.4% of patients).

There is a need for large, randomized trials to identify which components or combinations of components are most effective. There is a need to identify techniques to improve patient outcomes during the maintenance phase in trials for the long-term control of lymphedema.

• Risk of bias (no control group)
• Risk of bias (sample characteristics)
• Findings not generalizable
• Subject withdrawals ≥ 10%

Nurses should be aware of this intervention as a potential treatment for patients with lymphedema, making this an important point of education. The early identification of lymphedema using \"heaviness\" as a descriptor may help refer patients for treatment sooner. The fact that results may diminish after intensive treatment should be considered, and this could point to the importance of adhering to strict maintenance schedules and encouraging physical activity for long-term benefits.

The study evaluated soy phytoestrogens for the treatment of hot flashes in breast cancer survivors.

After a baseline documentation week, women received four weeks of either soy tablets or placebo. They then crossed-over to the opposite for the last four weeks. The soy product was formulated in 600 mg tablets. Participants took one tablet three times per day (150 mg of isoflavones day), an amount similar to that consumed with three glasses of soy milk.

Participants included 177 women with a history of breast cancer; 149 participants (84%) provided useable efficacy data for the entire nine weeks of the study.

All participants were randomized in a double-blind crossover design to one of two groups (soy or placebo) and crossed-over after four weeks. Participants were stratified according to age, duration of hot flashes, and the average daily hot flash frequency using a dynamic allocation procedure that balances marginal distributions. They were also stratified by current tamoxifen or raloxifene use (yes or no).

The instrument was a daily questionnaire documenting hot flashes frequency, intensity, and perceived side effects.

The soy product did not alleviate hot flashes in breast cancer survivors. No toxicity was observed. These data failed to suggest any patient preference for the soy compound over the placebo preparation.

Optimal daily dose of soy required to recognize a clinical response may be questioned. Data related to estimated intake of 150–200 mg daily in the Asian diet endorsed the choice of 150 mg/day. Experience from conventional HRT suggests that length of time on the soy isoflavones (four weeks) may be too short to elicit a clinical response. Study durations of less than three months have been excluded from overviews of the effects of HRT.

To reduce anxiety caused by chemotherapy (not the diagnosis)

The intervention was reflexology foot massage in hospitalized patients undergoing their second or third cycle of chemotherapy (30-minute foot massage on both feet by an RN student). The Spielberger State-Trait Anxiety Inventory was administered before and after reflexology and 24 hours post-reflexology.

The study reported on a sample of 30 patients: 15 in the control group and 15 in the reflexology foot massage group.

Italian research hospital

Spielberger State-Trait Anxiety Inventory

There was an average decrease of 7.9 points on the state-anxiety scale in the treatment group (p < 0.0001) after the short time frame (immediate decrease in anxiety).

• The study had a small sample size.
• The sample was not randomized, and patients were not categorized by cancer diagnosis, stage, or presence of metastasis.
• The study used a specially trained reflexology practitioner.

• FINAL NUMBER STUDIES INCLUDED = 4
• TOTAL PATIENTS INCLUDED IN REVIEW = 94 
• KEY SAMPLE CHARACTERISTICS: All four studies reviewed the application of leuprolide acetate (LA) at varying doses and timing in premenopausal females undergoing bone marrow transplant (44) or stem cell transplantation (30), or who were at risk of bleeding due to hematologic malignancy or therapy-induced thrombocytopenia (20).

PHASE OF CARE: Active antitumor treatment

In the four studies reviewed, the administration of LA in premenstrual women with hematologic malignancy at risk of bleeding demonstrated efficacy in reducing episodes of uterine bleeding. The route of administration (IV, IM, or SQ) did not appear to have an effect upon efficacy. Efficacy was improved when LA was administered at least two weeks prior to the onset of thrombocytopenia.

Leuprolide acetate administration to premenopausal women at risk of uterine bleeding demonstrates efficacy in the prevention of uterine bleeding. In addition, there was no documentation of adverse effects from the hormone.

The number of studies and participants included was small (4 and 94, respectively). In addition, there was not a randomization of participants.

Uterine bleeding in premenopausal females undergoing therapy for hematologic malignancy poses a significant risk. Administration of LA has the potential to mitigate this. There is a place for further research to define dose, administration, and timing of administration.