To examine the effectiveness of two interventions to ameliorate diarrhea after treatment with irinotecan

• 2 g AST-120 (Kremezin™) oral adsorbent made of activated carbon given at the start of irinotecan infusion, immediately after irinotecan, and 3 hours later
• An oral alkalization made of 2 g NaHCO₃ (sodium bicarbonate), 2 g magnesium oxide, and 300 mg ursodeoxycholic acid given orally before irinotecan infusion and then every day for three days after

This was a nonrandomized trial of 13 Japanese patients with various cancers receiving 60–100 mg/m² irinotecan every one to two weeks, alone or in combination regimens. Patients received one of three interventions. Four patients received AST-120; one of these four had previously received irinotecan with no prophylaxis and thus served as a control. Four patients received the oral alkalization; one of these also had previously received irinotecan with no prophylaxis and thus served as a control. Including these two controls, a total of seven control patients received irinotecan with no prophylaxis.

The number of bowel movements was recorded; however, volume was not recorded.

Oral AST-120 was associated with significantly decreased numbers of daily bowel movements during irinotecan treatment compared to no prophylaxis (p < 0.05). Oral alkalization was effective in ameliorating diarrhea, but the difference was not significant.

• The sample size was very small with only 13 patients.
• One patient in the AST-120 group and one in the oral alkalization group acted as their own controls. Only three other patients were in each interventional treatment  group.
• Although further study is necessary regarding the effectiveness of oral AST-120 on plasma concentrations of irinotecan-related compounds, the absorption of irinotecan or SN-38 from the intestinal lumen is small, if any, and the remaining irinotecan-related compounds in the intestinal lumen cause diffuse mucosal damage in irinotecan treatments.

To conduct a secondary data analysis from the MELODY trial to determine if 6 mg of oral melatonin administered at bedtime pre- and postsurgery would improve objective and subjective sleep outcomes in patients with breast cancer

The original study design was a randomized, double-blind, placebo-controlled trial to test the effect of melatonin on depressive symptoms. Participants randomized to melatonin or placebo taken at bedtime for three days prior to surgery and continued until 12 weeks postoperative. Secondary data points for sleep are described in this article. No baseline sleep assessment was reported, and time points of subjective and objective data collection were preoperative night 2/3, preoperative night 1, postoperative night 1/2/3, postoperative night 4/5/6, and night before histology information, normally two weeks postoperative.

• N = 48  
• MEAN AGE = 55 years
• AGE RANGE = 34–74 years 
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Nonmetastatic breast cancer 
• OTHER KEY SAMPLE CHARACTERISTICS: All participants were surgical patients scheduled for mastectomy or lumpectomy with sentinel node dissection with and without axillary dissection.

• SITE: Single site    
• SETTING TYPE: Not specified    
• LOCATION: Herlev Hospital, Copenhagen, Denmark

• PHASE OF CARE: Active antitumor treatment

• Secondary analysis of effect of melatonin on subjective and objective sleep  pre- and postsurgery

Subjective measures included visual analog scale for subjective sleep quality (0 mm = best possible sleep and 100 mm = worst sleep). The Karolinska sleepiness scale (KS) was used to assess level of sleepiness using nine-point scale (1 = very alert, 10 = very sleepy). No psychometric properties were provided. Objective sleep actigraphy data were guided with a sleep diary for parameters of efficiency, time in bed, total sleep time, wake after sleep onset (WASO), latency, and awakenings. Actigraphy was recorded for the entire study period.

Evaluation of objective sleep outcomes from actigraphy revealed no significant differences for preoperative sleep or wake outcome variables postoperatively and prehistology. Sleep efficiency was higher in the treatment group (p < 0.03). WASO was significantly lower in the postoperative times of 1/2/3 and 4/5/6 in the melatonin group (p < 0.03). No significant differences were found in the subjective measurements (sleep, pain, KSS) preoperatively and postoperatively.

Use of oral 6 mg of melatonin one hour before bed significantly increased efficiency in the three postoperative time points, and WASO decreased during the postoperative time points. However, subjective sleep and pain did not improve. Melatonin use needs to be further evaluated as this study had several limitations.

• Small sample (less than 100)
• Measurement validity/reliability questionable
• Findings not generalizable
• Questionable protocol fidelity
• Subject withdrawals of 10% or greater
• Appropriateness of study statistical plan is questionable.
• The active and placebo groups differed on the duration of surgery and anesthesia; since one of the three-day sleep periods included postoperative nights one, two, and three, the duration of anesthesia may have affected sleep and other outcomes in the first postoperative night, which should have been accounted for or addressed in the Limitations section.
• The rationale for 6 mg dose is missing.

Nurses need to inquire about pre- and postoperative use of any medications to understand and counsel patients and family members on evidence that would support the use of the medication. Melatonin may be helpful to improve sleep, but additional studies are needed.

Determine the effect of essential oil mouth rinse on mucositis onset, pain, and oral symptoms; weight loss

Patients were randomized to treatment, placebo, and control groups. Placebo and intervention groups were given solutions in 25 mL amber bottles with dropper caps. Patients in the treatment group were provided with a 1:1 mix of manuka and kanuka oils; placebo was sterile water. The participants further diluted and gargled for at least 15 seconds, then spit out. Then a fresh prep of same dilution was swallowed. This was started two days before radiation treatment began, and continued until one week after the completion of radiotherapy. Patients were to gargle 30 minutes either before or after eating, smoking,or drinking and before and after each radiotherapy treatment. Control patients did usual care.

The sample was comprised of 19 patients. Intervention n = 6, placebo n = 6, control n = 7. The mean age was 68.9, with a range of 45-81 years. Females active = 1; placebo = 4, males active = 5, placebo = 2, control = 7.

Diagnosis Information: all head and neck cancer; all undergoing non-palliative radiotherapy to the oropharyngeal area.

Other Key Characteristics: Mean radiation dose across groups ranged from 5933-6200 cGy.

Single site: Outpatient setting New Zealand; large center with 7-9% of new patients with head and neck dx/year

Randomized placebo double-blind controlled trial

Patient diary: pain score, medication use, oral symptoms, 10 point visual analogue score (pain) RTOG 0-4 scale; body weight post-discharge survey (dry mouth/cough; altered taste and appetite; excess secretion/nausea and vomiting rating on scale of 0-10)

All patients developed some mucositis. The active gargle group went the longest time before a reaction occurred (p = 0.05). Onset of pain was reported to be delayed in the treatment group; only 1% of patients had a weight decrease in the treatment group compared to a 5.2% loss in the control group and a 4.1% loss in the placebo group.

Because this was a feasibility study, there is no statistical analysis of the results. The results support the hypothesis that these oils may provide a positive effect on the development of mucositis, pain, and nutritional outcomes.

Small sample <30. Need for participants to adhere to gargling; frequent performance of intervention; multiple clinicians evaluated mucositis.

Further research is needed to determine the overall benefit of this intervention.

The effect of three test mouthwashes and a control were studied.

1. 0.12% chlorhexidine
2. 1% povidone-iodine
3. salt/sodium bicarbonate
4. plain water (control)

Coloring agents, sweeteners, and flavoring agents were added to the mouthwashes so that all had identical color and taste. All were alcohol free.

Patients rinsed mouths with 10 ml of mouthwash BID for six weeks. Patients swished for about two minutes and expectorated, then abstained from eating or gargling for 30 minutes.
 

The study was comprised of 20 patients in each arm of study.

Adult patients with stage II–IV head and neck malignancy scheduled to receive RT of 60 Gy or higher, delivered in 30 fractions over a six-week period.

At least one-third of oral cavity mucosa was included in the radiation field.

Powered for 20 subjects in each arm; 76 completed.

The median age was 54.25–58.2 years.

More men participated than women.
 

July 2003–January 2004

Double-blind, placebo-controlled, randomized clinical trial

Compliance was assessed weekly by checking the level of mouthwash left in bottles.

Mucositis WHO– single examiner

Primary endpoint of study was the end of week 6.
 

Significant difference in mean mucositis scores was observed among all four groups. Post hoc analysis for repeated measure showed a statistically significant difference between the povidone group and control group (p = 0.013) at the end of week 1.

At the end of week 2, povidone, chlorhexidine, and salt/soda groups differed significantly from the control group.

At the end of week 4, significant differences also were observed between the povidone and salt/soda groups (p = 0.16).

At the end of week 5, significant differences were observed between all test groups and the control group. Differences also were observed within test groups.

At the end of week 6, a slightly different trend was observed. Significant differences were observed between the povidone group and all other groups; difference in mucositis among other groups was not statistically significant.
 

Although the volume of solution used was checked weekly, data does not indicate compliance.

No data is available regarding treatment delay.
 

To evaluate the effect of a hydrogel or dry dressing on the time to healing of moist desquamation after radiation therapy

Participants were randomly assigned to either dry dressing or no dressing (Tricotex) or hydrogel (intrasite) dispenser at the beginning of radiation therapy. Patients received the same instruction of skin care and were provided with simple soap. Patients were instructed to use their dressing from the onset of moist desquamation, if it occurred.

• The study sample (N = 100) was comprised of male (n = 30) and female (n = 70) patients with breast (n = 10), head and neck (n =30), or anorectal cancer (n = 60) who developed moist desquamation.
• Most patients were aged less than 50 years in the hydrogel (55%) and dry dressing (50%) groups.
• Patients with breast cancer had a tangential field separation of greater than 22 cm.
• Patients were excluded if they had a previous skin reaction to chemotherapy.

The study took place at multiple sites in Scotland.

The study used a randomized controlled trial design.

• Patient perception was measured completing daily diary cards that detailed the degree to which they experience pain, itching, burning, and sleep disturbances.
• Participants rated the appearance of their skin reaction using a desquamation scale that allowed them to score whether their skin was dry or scaly, broken, or weeping in small or large patches.
• Researchers used a modified Radiation Therapy Oncology Group and European Organisation for Research and Treatment of Cancer (RTOG/EORTC) scale weekly until the skin was healed.

• Moist desquamation occurred in 48% of all radiation therapy patients and reviewed mean time was 32 days, with a range of 16–50 days.
• The reaction occurred in 47% of patients before the end of treatment and 39% during the final week. In 38%, the reaction occurred after the end of treatment.
• Moist desquamation was confirmed earlier to those randomized to hydrogel dressings.
• Desquamation scores improved more in patients not assigned to hydrogel dressings.
• Skin reactions healed much more slowly in those assigned to hydrogel dressings (p = 0.03)
• In anorectal cancer cases researcher and patient scores showed they experienced more severe reactions than the other groups and both reactions were significantly worse for those who used hydrogel than those who were assigned to the dry dressing.
• Although variables such as body mass index and smoking, concurrent chemotherapy, bolus use, and total radiation dose were predictive of development of moist desquamation, these variables did not influence demonstrated time to healing.

The study does not support the routine use of hydrogel in the care of patients with moist desquamation and suggests that the healing times are prolonged, without any improvement in patient comfort.

• Hydrogel dressing was more costly than the dry dressing.
• Modified RTOG/EORTC scale was not an established measure and precludes comparison to other studies.
• Patient self-rating scales were not fully described.
• The sample size for head and neck and breast cancer cases was small.
• Although 100 cases were reviewed, only 48% actually would have used the assigned treatment.
• The control group combined dry or no dressing.

• FINAL NUMBER STUDIES INCLUDED = 8
• TOTAL PATIENTS INCLUDED IN REVIEW = 444
• SAMPLE RANGE ACROSS STUDIES: 19–189 patients

PHASE OF CARE: Late-effects and survivorship
 
APPLICATIONS: Palliative care

All of the evidence was reported as low with levels of 3 or 2 (specific grading scale not described). Response rates varied from 0%–69%. Six of the studies included were retrospective case series. Two studies did not document pain, and three studies did not use any clear measure of pain.

The effectiveness of radiotherapy for pain palliation in this group of patients is unclear.

• Relatively few studies
• Low-level evidence due to study design issues

Evidence regarding the effectiveness of radiotherapy for the treatment of pain from malignant pleural mesothelioma is lacking. Further well-designed research using valid tools for pain measurement is needed.

To use a systematic literature review and meta-analysis to evaluate interventions using Cannabis sativa in the treatment of chemotherapy-related nausea and vomiting

Databases searched were MEDLINE, Embase, PsycINFO, LILACS, and the Cochrane Collaboration Controlled Trials Register (12-2006).

Searched keywords were Medical Search Headings (MeSH) therapeutics, drug therapy, chemical and pharmacologic phenomena, neoplasms, antineoplastic and immunosuppressive therapy, marijuana abuse, cannabis, randomized controlled trials, and clinical trials.

Studies were included in the review if they

• Were randomized clinical trials (RCTs).
• Involved people with any type of cancer receiving chemotherapeutic treatment of low-, moderate-, or high-emetic potential.
• Were published in peer-reviewed journals.
• Evaluated pharmacologic interventions based on substances derived from Cannabis sativa or smoked Cannabis.

Studies were excluded from the review if they involved patients receiving radiotherapy.

The initial search yielded 12,749 papers. After scanning titles for inclusion, 735 abstracts were evaluated. Of these, 96 papers were reviewed and a final sample of 30 RCTs were included in the review.  RCTs that were appropriate for meta-analysis numbered 13. Studies were rated for quality using the Cochrane Manual for methodological quality evaluation in terms of bias risk.

• A final sample of 30 studies was included in the systematic review, and 13 studies were included in meta-analysis.
• Sample sizes varied among studies, with only six studies involving more than 100 patients.
• Across studies, the total sample size was 1,719.

• Two studies comparing dronabinol to placebo showed a trend favoring dronabinol, but it was not significant (p = 0.10).
• In five studies comparing dronabinol to neuroleptics, dronabinol was significantly better than the comparisons (relative response [RR] = 0.67, p = 0.03).
• In six studies comparing nabilone to neuroleptics, no significant differences were found.
• Four studies comparing levonantradol to neuroleptics showed no differences.
• In 18 studies composed of 1,138 patients, participants had a significant preference for cannabis (RR = 0.33, p < 0.00001).
• All of the studies had low or only moderate risk of bias.
• Patients taking cannabinols had a higher number of collateral effects and tended to have higher symptom intensity.

• Most patients preferred cannabis-based treatment when asked about their preferred drug.
• Different cannabis derivatives demonstrated different effectiveness when compared to standard treatment used at the time.
• Newer and more effective approaches for management of nausea and vomiting have emerged in practice since these studies were conducted.
• Comparative effectiveness of cannabis derivatives versus these approaches is unknown.

• If patients do not respond to antiemetics or they experience increased emesis after taking antiemetics, increased dosage or frequency of administration is not recommended.
• Because cannabinoids appear to act through different mechanisms than other drugs, they may be effective for people with nausea and vomiting that does not respond to other management approaches. 
• Clinical trials comparing cannabinoids to modern antiemetics are warranted.

The study looked at soy supplements versus placebo for treatment of menopausal symptoms in participants with early breast cancer and hot flashes.

Participants were randomized to receive either two soy capsules or two identical placebo capsules twice daily for 12 weeks in a double-blind fashion. The soy capsules each contained 235 mg of soy extract with 17.5 mg of isoflavones. Total dose of isoflavones was 70 mg/day. 

Seventy-two (72) participants with early breast cancer and hot flashes were randomized to 12 weeks of treatment with soy capsules or with placebo. To be considered a worthwhile treatment strategy, soy extract would need to benefit around half of the participants treated. Thus, 32 evaluable participants per arm were needed.  The median age was 51 years. Any concomitant medications for preexisting disease were allowed.

The randomized double-blind controlled trial was stratified for initial sweating/flushing score (< 2, p = 2); age at randomization (younger than 50 years, older than 50 years); currently having adjuvant tamoxifen or after ovarian suppression (yes or no).

QOL and menopausal symptoms scores were assessed at baseline and weeks 4, 8, and 12. A four-question menopausal scale was developed for the study to assess control of menopausal symptoms measured by combined estimates of severity of sweats (day or night) and flushes.

There was no significant difference in menopausal symptoms between the placebo and soy capsule arms of the study.Toxicity was mild and primarily gastrointestinal. There was no significant difference in toxicity between the 2 arms.

To determine pharmacokinetics (PK) and efficacy of oral mesna

Patients were given IV mesna for the first dose and then randomized to IV or oral mesna for the following two doses. Crossover occurred at cycle two.

• N = 7 patients given ifosfamide 2g/m²/day for five days—16 evaluable for POB

• Phase I/II randomized crossover design of IV/oral mesna
• Patients crossed over after first cycle
• Study ran over two full cycles of chemotherapy

• Urine sampling and serum sampling for PK 
• Weekly complete blood counts, serum chemistry, and urinalysis

There were no significant differences in plasma PK between IV and oral. Rates of HC were not significant among IV and oral arms (3 of 16 for IV/IV/IV arm (90% CI 0.15 – 0.34) and 4 of 16 for IV/PO/PO arm (90% CI 0.23 – 0.52). Measurement of HC was not clearly defined.

• Small sample size
• Crossover design gives more power and eliminates P-450 differences—power not addressed and so would decrease in LOE from I to II

To evaluate domicile-based humidification on mucositis symptoms associated with radiation in patients with head and neck cancer

Inpatients were randomized 1:1. The control group (n = 100) received the institutional standard of care for managing mucositis (as defined by each institution), and the intervention group (n = 103) received the standard of care plus domicile-based humidification with the Fisher & Paykel Healthcare MR880 humidifier. The humidifier was set at 37°C and 100% relative humidity. 44 mg of vaporized water per liter of air was delivered via nasal prongs. Sensors were used for continuous feedback and to optimize delivery and prevent condensation. The rate of flow was selected to promote some leakage of moisture into the oral cavity and began at 25 L per minute. Flow was increased 30 L per minute if tolerated by the patient. Humidification began on the first day of radiation therapy with continuous use at night and additional use during the day. The intervention continued for 12 weeks. Patients who had a mucositis score ≥ 2 at week 12 continued the intervention until his or her score was < 2 or until week 16, whichever occurred first. The electronically recorded compliance was set with four hours of daily humidifier use as the benchmark. Data were recorded weekly until week 12 for all patients and weekly until week 16, or until mucositis scores were < 2, for some patients. Additional data were collected at weeks 12 and 20.

• N = 203            
• AGE = Patients were all ages 
• MALES: 164 (80.8%), FEMALES: 39 (19.2%)
• KEY DISEASE CHARACTERISTICS: Head and neck cancer

• SITE: Multi-site 
• SETTING TYPE: Outpatient  
• LOCATION: Eleven participating institutions across Australia and New Zealand

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

Randomized, controlled trial

• National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI, CTCAE) version 3.0
• McMaster University Head and Neck Radiotherapy Questionnaire (HNRQ) 
• MD Anderson Symptom Inventory Head and Neck Module 
• Fiberoptic endoscopic examination

High, medium, and low humidifier compliance rates were reported in 23, 20, and 60 patients, respectively. Per protocol (PP) patients were those in the medium and high compliance groups. The difference in compliance was significant between institutions (range = 0.11–0.74, mean = 0.37, p = 0.004). The mean number of hours the intervention device was used was 3.6 hours (range = 0–14 hours). Differences in the institutions' ​area under the curve (AUC) for mucositis scores ≥ 2 were significant (range = 6.87–11.87, p = 0.008). There was no difference in the AUC in CTCAE scores. There was a difference between groups in PP functional mucositis scores ≥ 2 (p = 0.009) and ≥ 3 (p = 0.006).

Humidification can decrease the severity of mucositis and decrease the time to healing of ulcerated mucositis. Unfortunately, there was a low rate of compliance with the home-based humidification intervention. Patients in the study cited the following reasons for disliking the intervention: dislike of high-flow rate, heat, plastic nasal interface odor or bore size, and noise during the night. The study also showed that patients who reported the highest satisfaction with the humidifier were those who had the most symptom relief from its use.

• Risk of bias (no blinding)
• Other limitations/explanation: High rate of noncompliance with intervention

Patients who were compliant with the intervention saw a reduction in the severity of mucositis and faster healing of oral ulcers. The majority of patients enrolled, however, reported low compliance with the intervention for a variety of reasons. The use of a humidifier at home may appeal to some patients. Nurses can play an important role in assessing if patients are ready to make a life change that includes an intervention such as this one. Patients who were compliant with the intervention reported more symptom relief than patients who were not compliant.