Patients were treated with acetyl-L-carnitine (ALC) 1 g per day via IV for at least 10 consecutive days. Cisplatin neuropathy was characterized as numbness, tingling, loss of vibration sensation, and diminished proprioception.

• The sample consisted of 27 patients with paclitaxel- or cisplatin-induced chemotherapy-induced peripheral neuropathy (CIPN) aged 48–75 years.
• Potential participants were excluded if they had a European Cooperative Oncology Group performance status greater than 2 or preexisting neuropathy (not CIPN).

The study was conducted from April 2000 to December 2002.

• CIPN severity was graded using the World Health Organization toxicity grading scale.
• Clinical neurologic assessment was preformed at baseline and at the end of ALC treatment.

Of the 26 patients, 19 (73%) showed at least one grade of CIPN improvement, and all cisplatin-treated patients showed at least one grade of CIPN improvement. In addition, one patient with World Health Organization grade 2 neuropathy had complete resolution of neuropathy after 11 days of treatment. For paclitaxel-treated patients, 8 of 12 (67%) showed one grade improvement, as did 8 of 10 (80%) in the combination paclitaxel and cisplatin treatment group. The remaining patients had stable CIPN.

• Limitations included a small sample size (27 enrolled, 26 with data for analysis); the non-randomized, non-blinded design; and no control group, because of which no causality can be inferred.
• Whether the clinical neurologic examinations were conducted by the same physician using a standard approach or by different practitioners is unclear.
• No information concerning inter- or intrarater reliability was provided.
• The parameters tested and methods used to conduct the clinical neurologic testing was not provided.
• The number of variables used in the statistical tests also are unknown, making it difficult to evaluate the conclusions.

To evaluate the safety, efficacy, and pharmacokinetics of palonosetron, in combination with dexamethasone in patients receiving highly emetogenic chemotherapy (HEC)

Patients were randomized to 1 of 3 single doses of palonosetron, IV bolus (0.075, 0.25, or 0.75 mg), before administration of HEC. Subjects also received dexamethasone (12–16 mg IV on day 1, 8 mg on day 2, and 4–8 mg on day 3). All patients were hospitalized at least one day after palonosetron administration. Patients were followed up to five days. Patients used a diary to record episodes of vomiting, degree of nausea, and use of rescue medication.

• The study consisted of 231 participants.
• Mean age was 61.7 years (SD = 8.9) for the 0.075 mg group, 62.1 years (SD = 8.8) for the 0.25 mg group, and 62.0 years (SD = 9.8) for the 0.75 mg group.
• The majority of patients were male (73.2%).
• The majority of patients had lung cancer (95%), primarily non-small cell lung cancer (NSCLC).
• Patients were receiving cisplatin ≥ 50 mg/m².
• Patients were either chemotherapy naïve or had only received low or minimally emetogenic chemotherapy previously.

The study was conducted at multiple sites in Japan.

All patients were in active treatment.

This was a randomized, double blind, dose-ranging study.

• Patient diaries were used to record the date and time of emetic episodes, degree of nausea on a 0–3 scale, and use of rescue medication.
• Complete response (CR), defined as no emesis and no rescue medication, was recorded during the acute, delayed, and overall phases.
• Complete control (CC), defined as no emetic episodes, no rescue medication, and no more than mild nausea, was recorded during acute, delayed, and overall phases.
• Time to treatment failure, including time to first emetic episode or first administration of rescue medication, was recorded.
• Adverse events using Common Terminology Criteria for Adverse Events (CTCAE) were recorded.
• Pharmacokinetic analysis (palonosetron and M9 in plasma for the maximum plasma concentration, area under the curve, terminal half-life, total clearance, volume of distribution) was conducted.

• CR rates during acute phase were 77.6%, 81.8%, and 79.5% in all groups, without significant differences in different dose groups.
• CR rates increased in a dose-dependent manner during the delayed and overall phases.
• CR rates in the delayed phase were 38.3%, 49.4%, and 56.4% respectively by dose group.
• Time to treatment failure was significantly longer in the 0.75 mg group than 0.075 mg group (p = 0.0376).
• The incidence, intensity, and relation of adverse effects to palonosetron were similar among the three dose levels.
• The most frequent adverse events were constipation and headache, and most adverse events were mild to moderate.

Palonosetron at doses of 0.25 mg and 0.75 mg was shown to be effective in preventing chemotherapy-induced nausea and vomiting (CINV) in the acute phase in patients treated with HEC. CR rates in the delayed phase were less than 60% overall.

• The study did not include administration of aprepitant for HEC-related CINV.
• No discussion was provided regarding participant compliance with keeping the diary, which was the main measure for CR.
• The CR definition did not address nausea experience, and CC was not reported in detail, which addresses nausea control.

Increasing the dose of palonosetron on day one could contribute to better control of CINV during the delayed and overall phases of HEC.

To explore the effect of a previously developed Japan Outreach Palliative Care Trial of Integrated Regional Model (OPTIM) intervention on palliative care outcomes (quality of patient death and dying, family views on patient quality of care and pain control, and caregiver burden) in hospital, home, and palliative care unit settings

The OPTIM intervention focused on enhancing Japanese regional medical providers’ palliative knowledge and skills via distributions of manuals and interactive workshops and incorporating palliative care teams in educational outreach to community patients and families. The intervention also focused on holding interdisciplinary palliative care conferences and providing consumer-based information and programs on palliative care to improve regional oncologic comfort. Patients and caregivers from 23 hospitals and home-care clinics completed four questionnaires in a mailed survey sent before and following the intervention.

• N = 2,247    
• AGE: 72% aged 69 years or younger (no mean age reported)
• MALES: 29.65%, FEMALES: 70.35%
• CURRENT TREATMENT: Other
• KEY DISEASE CHARACTERISTICS: Diverse cancers (lung/gastrointestinal were most common) to support patient terminal illness 
• OTHER KEY SAMPLE CHARACTERISTICS: Caregivers were adults, able to complete questionnaires, and did not have severe emotional distress. Two different groups of caregivers responded to pre- and postintervention surveys.

• SITE: Multi-site   
• SETTING TYPE: Multiple settings    
• LOCATION: Japan

• PHASE OF CARE: End-of-life care
• APPLICATIONS: Palliative care

Pre-/postdesign

• Care Evaluation Scale to measure 10 domains of family-perceived quality of patient care
• Good Death Inventory to measure 18 domains of a good death in Japanese patients with cancer, included one item to measure patient pain relief 
• Caregiving Consequences Inventory to measure care burden

Significant differences (p < 0.01) were reported in quality of patient care in the home, palliative care unit, and hospital, with highest quality of care in the home. Overall, quality of care improved significantly (p = 0.04) from preintervention to postintervention in hospitals. Similar improvements at a significant level (p = 0.012) occurred in the quality of death and dying in hospitals, although this place had the lowest score at baseline compared to palliative care units and the home. No significant differences in patient pain relief occurred pre- and postintervention, nor did caregiver burden significantly increase postintervention in any of the three settings of patient death. Quality of care measures in the hospital and in some measure domains in the palliative care unit increased significantly postintervention (p < 0.05).

Caregiver quantitative feedback postintervention showed the most improvement in quality of care and of death and dying in hospitalized patients, with additional improvement in palliative care units deemed as high quality by caregivers preintervention. Caregivers consistently viewed home care as highest in quality pre- and postintervention. Family burden of care did not increase in the three settings related to the intervention. With most patient deaths in hospitals in Japan and many countries, additional efforts to improve hospital quality of care may smooth the transition of dying patients to their homes for improved family well-being.

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (sample characteristics)
• Unintended interventions or applicable interventions not described that would influence results
• Key sample group differences that could influence results
• Findings not generalizable
• Only definition of patient status was “terminally ill”
• Caregivers required to provide data in retrospective manner when recall may have been difficult
• Response rate of three groups differed to affect measurement of quality of care and quality of patient death and dying.
• Definition of family caregiver unclear in article (more than 92% of caregivers were spouses or children of the patient)
• Significant differences in age of patients and caregivers existed in preintervention and postintervention groups, and similar significance existed in place of death in both groups.
• Specifics of intervention unclear because of earlier publication of that information

Current emphasis on the delivery of high quality care to patients and their families in a variety of end-of-life settings mandates nursing attention to the feedback of patients who are terminally ill and their caregivers to meet that goal. Additional research and evidence from clinical practice offer opportunities to gain that feedback to improve care at the end of life for patients with cancer and their families.

To examine the effectiveness of two interventions, AST-120 and oral alkalization, to ameliorate diarrhea after treatment with irinotecan

• Patients with varying cancers who were receiving irinotecan were given AST-120, oral alkalization, or nothing (control).
• AST-120 (Kremezin™) is an oral adsorbent made of activated carbon. Patients received 2 g at the start of irinotecan infusion, immediately after irinotecan infusion, and three hours after irinotecan infusion.
• Oral alkalization, consisting of 2 g NaHCO₃ (sodium bicarbonate), 2 g magnesium oxide, and 300 mg ursodexycholic acid, was given before irinotecan and then daily for three days after irinotecan administration.

The study reported on 13 Japanese patients with cancer receiving 60–100 mg/m² irinotecan every 1–2 weeks, alone or as part of a combination regimen. The control group consisted of 7 patients, the AST-120 group consisted of 4 patients, and the oral alkalization group consisted of 4 patients. One patient in each of the two intervention groups served as his or her own control, having received prior irinotecan with no prophylaxis.

This was a nonrandomized trial.

Patients recorded the number of bowel movements but not the volume.

• Oral alkalization appeared to be effective in ameliorating diarrhea, although the efficiency did not reach a significant difference (level of significance not indicated).
• AST-120 significantly decreased the maximum number of daily bowel movements during irinotecan treatments as compared with no prophylaxis (p < 0.05).

• This was a small study with only 13 patients.
• One patient in the AST-120 group and one patient in the oral alkalization group acted as his or her own control. Only three other patients were in each interventional treatment group.

Although further study is necessary regarding the effect of oral AST-120 on plasma concentrations of irinotecan-related compounds, it is speculated that 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 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.