To investigate if Ruta graveolens 9c can improve quality of life and reduce tumor progression in patients with advanced disease.

Ruta graveloens is a medicinal plant that has been historically used to treat various inflammatory conditions Ruta graveloens was given at a 9c dilution in 1 ml ampules. The extract was taken orally twice daily for eight weeks. Patients continued treatment until there was tumor or clinical progression. Study data were obtained on day 1 and at weeks 8, 16, 28, 40, and 52. Examination and tumor markers were evaluated every four weeks.

• N = 31
• MEAN AGE = 64.3 years (range = 44-87)
• MALES: 33%, FEMALES: 77%
• KEY DISEASE CHARACTERISTICS: Various tumor types, breast cancer most predominant; 64.5% had progressive disease
• OTHER KEY SAMPLE CHARACTERISTICS: Most had performance status lower than 1. At baseline, 70% had clinically relevant anxiety scores and 63% had relevant depression scores

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

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

• Quasi-experimental, open label

• EORTC QLQ-C30
• Hospital Anxiety and Depression Scale 
• Tumor markers and imagery 
• NCI CTCAE version 4

Quality of life improved by week 8 (p < 0.001) and week 16 (p = 0.035). There were no significant changes in anxiety or depression scores. Mean duration of treatment was 3.3 months and median progression free survival was 1.9 months. Ninety percent had at least one adverse event, with an average of nine events per patient. Most comment symptoms were abdominal pain, fatigue, musculoskeletal pain, and headaches. None of the events were considered to be related to the study treatment.

Treatment with Ruta graveolens 9c did not have a demonstrable effect on anxiety or depression.

• Small sample (less than 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
• Other limitations/explanation: It is not stated whether any patients were receiving antidepressants or anti-anxiety medications or other interventions that could have impacted quality of life and symptoms

Ruta graveolens did not have an effect on anxiety or depression in this study.

To compare effervescent morphine to immediate release (IR) during breakthrough pain

Dosage adjustments of fixed schedule opioid could be made at the discretion of the investigator. Patients documented onset time, efficacy, and side effects of IR morphine given for breakthrough pain for one month. They were to take it within five minutes of breakthrough pain and titrate until sufficient relief, starting at 20 mg (equivalent to one effervescent tab). For the second month, the patients took effervescent morphine. They were instructed to take it within five minutes (they could take an additional one after 10 minutes) up to a max of four tabs for a single breakthrough pain episode. Patients could take non-investigational drugs for control of adverse effects (e.g., nausea, constipation, sedation). This was a long-term study that lasted up to six months.

• N = 76
• MALES: 41, FEMALES: 35
• KEY DISEASE CHARACTERISTICS: Patients with cancer with chronic pain being treated for breakthrough pain
• OTHER KEY SAMPLE CHARACTERISTICS: 86% of breakthrough pain was related to tumor, 5.3% of patients had neuropathic pain. For primary pain treatment, multiple sustained-released (SR) opioids were used—fentanyl patch, 38.2%; morphine SR, 32.8%; transdermal buprenorphine, 11.8%; oxycodone SR, 14.4%; and hydromorphone, 5.3%.

• LOCATION: Germany and the United States

• Open-label safety and efficacy study

• Time until pain relief, global satisfaction, side effects, efficacy, and long-term safety of effervescent formulation
• An episode was treated sufficiently when adequate pain relief occurred, defined as a visual analog scale (VAS) score of 3 on a 0–10 scale.
• Patients completed questionnaires and kept daily diaries.
• Number of breakthrough pain episodes
• Pain relief using VAS
• Global satisfaction scale using a five-point Likert scale from 0 (poor) to 4 (excellent)

During the IR morphine month, the mean VAS score was 8 and decreased to 3. During the effervescent morphine month, the mean VAS score of 7.8 decreased to 3.2. No statistically significant difference was seen between IR morphine and effervescent morphine; however, the difference was significant (p < 0.001) when comparing pain intensity prior to taking effervescent morphine. The time to relief with effervescent morphine was 13 minutes and 27 minutes with IR morphine (statistically significant, p < 0.001). Effervescent morphine decreased the number of breakthrough pain episodes from a mean of 3.3 per day to 2 per day. This was statistically significant (p < 0.01).

• Dosage adjustments of fixed-schedule opioids could be made at the discretion of the investigator. No formal guidelines were used to make these adjustments.
• The definition of pain relief was VAS of 3. This may not be an adequate pain relief level for all patients.
• The non-investigational drugs given to treat adverse effects were not standardized or monitored.
• Only opioid-responsive patients were included in the study.
• Historical data was used for the IR morphine month and was compared to the effervescent morphine month. The study should have used a concurrent, double-blinded, randomized, cross-over design.

Although effervescent morphine had a faster onset, it does not compare with the onset of transmucosal fentanyl citrate (7–10 minutes).

A prospective study to compare the effect of an established laser therapy protocol with a potential therapy utilizing LED (light-emitting diode) on chemotherapy-induced oral mucositis

1. Physical examination was done on all patients and oral hygiene instructions were given to patients at the start of treatment.
2. Oral examinations were conducted during irradiation sessions and the degree of mucositis and pain were recorded daily.
3. Two different phototherapeutic protocols were used randomly from the time of the patient’s registration to 12–15 days later.
4. Patients received 10 consecutive days of irradiation, except for weekends.
5. Patients in group 1 received one laser phototherapy protocol of InGaAIP diode laser with a wavelength of 660 nm. Irradiation time was six seconds per point based on the laser beam spot size of 0.036 cm². Irradiations were performed intraorally: 12 points on each buccal mucosa, 8 on the superior and inferior labial mucosa, 12 on the hard palate, 4 on the soft palate, 12 on the lingual dorsum, 6 on the lateral edge of the tongue bilaterally, 2 on the right and left pillar of the tongue, 4 on the floor of the mouth, and 1 on the labial commissure bilaterally.
6. Patients in group 2 received one LED phototherapy protocol. The dentists were trained to perform LED irradiation in a standardized manner.
7. Irradiations were performed daily for 10 consecutive days, except for weekends, with a wavelength of 630 nm and with the same energy per point as was used in in laser protocol. Laser power was 40 mW, energy density of 6.6J/cm², power density of 1.1W/cm², and energy per point of 0.24J. Irridation was punctual, in contact, and perpendicular to the oral mucosa. Irradiations were performed intraorally in the same manner as for group 1.
8. For both radiation protocols before and after each session, power output was checked using a power meter.
9. Patient self-assessed pain was measured using a visual analog scale (VAS) for pain from 0 to 10 and was done prior to each laser/LED session.

• N = 4
• AGE RANGE: Group 1: 50.5 (+/– 14.7) years, Group 2: 57.4 (+/– 11.3) years 
• MALES: Group 1: 10 (44%), Group 2: 5 (29%) 
• FEMALES: Group 1: 13 (56%), Group 2: 12 (71%) 
• KEY DISEASE CHARACTERISTICS: Patients with chemotherapy-induced oral mucositis grades I, II, or III. Breast cancer was the most common cancer in both groups. A wide variety of chemotherapy were treatments used.

• LOCATION: Sao Paulo, Brazil

• PHASE OF CARE: Treatment
• APPLICATIONS: Patients with chemotherapy-induced oral mucositis grades I, II, and III

• Prospective trial

• World Health Organization (WHO) criteria for oral mucositis
• Visual analog scale (VAS) for pain (0 to 10)

• Beginning grade of mucositis did not differ between groups (p < 0.05).
• In the LED group, within-group analysis showed a significant decrease in mucositis from day 1 to days 7, 8, 9, and 10 (p < 0.05).
• In the laser group, within-group analysis showed a significant decrease in mucositis from day 1 compared to day 10 (p < 0.05).
• A trend was seen for both treatment groups. The higher the initial mucositis score, the more treatment that was required to improve mucositis. The trend was not statistically significant.
• Comparing the mucositis scores between the laser and LED groups according to patients initial mucositis grade, only in those patients with the initial mucositis score III (p = 0.028) was the LED treatment more effective in healing oral lesions than the laser treatment.
• Comparing the mean of VAS scores for laser and LED, according to the patients' initial mucositis scores, the LED treatment was more effective for patients with initial the mucositis scores I and II (p = 0.012 and p = 0.022).

Both therapies analyzed in this study were efficient in preventing breaks in treatment.

• The groups were not evenly matched for men and women.
• Risk of bias (no control group)
• Unsure how the randomization process was achieved; not stated in report
• Dentists were taught how to do WHO mucositis assessments, but the article did not speak to the training received.
• The LED power was twice as strong as the laser power, resulting in three and six seconds of irradiation per point, respectively. One advantage of the LED phototherapy protocol over the Laser protocol is that much less time is required to irradiate through the oral cavity.

LED phototherapy may be a viable alternative to traditional laser therapy to treat oral mucositis. This study, however, is small and has several flaws. Nurses should educate patients on proper oral hygiene to be used in combination with LED and laser therapy to promote optimal healing.

To provide a guide for the use of antimicrobial agents for chemotherapy-induced fever and neutropenia in patients with cancer. The patient population targeted included adult and pediatric patients with neutropenia.

For this guideline document, the IDSA Standards and Practice Guidelines Committee reconvened many members of their original guideline panel, together with additional experts, in the management of patients with fever and neutropenia. The committee included experts in infectious diseases, oncology, and hematopoietic stem cell transplantation (HSCT) in both adult and pediatric patients. The literature was reviewed and graded according to a systematic weighting of the level and grade of the evidence for making a recommendation.

Patients were undergoing the active treatment phase of care.

Antibiotic Prophylaxis 

Fluoroquinolone prophylaxis should be considered for high-risk neutropenic patients (patients expected to have absolute neutrophil counts (ANCs) of 100 cells/mm³ or lower for more than seven days. Levofloxacin and ciprofloxacin are the agents that have been evaluated the most and are generally equivalent, although levofloxacin is preferred for patients at risk for oral mucositis-related invasive viridans group streptococcal infection (B-1). The addition of a gram-positive active agent to fluoroquinolone prophylaxis is not recommended (A-1). Antibacterial prophylaxis is not indicated for low-risk patients anticipated to be neutropenic for less than seven days (A-III). 

Antifungal Prophylaxis

Patients at high risk for candida infection, such as recipients of allogeneic HSCT and patients with acute leukemia undergoing intensive chemotherapy, should be treated with antifungal prophylaxis with fluconazole, itraconazole, voriconazole, posaconazole, micafungin, or caspofungin (A-I). Patients aged 13 years or older who are undergoing intensive chemotherapy for acute leukemia or myelodysplastic syndrome who are at high risk for aspergillus infection may be treated with posaconazole for antifungal prophylaxis (B-I). Prophylaxis against aspergillus infection is not effective in recipients of pre-engraftment HSCTs, but it is recommended for patients with a prior history of invasive aspergillosis (A-III), anticipated neutropenia of at least two weeks (C-III), or a prolonged period of neutropenia prior to transplantation (C-III). Antifungal prophylaxis is not recommended for patients with an anticipated duration of neutropenia of less than seven days (A-III). 

Antiviral Prophylaxis

Herpes simplex virus–positive patients undergoing allogeneic HSCT or leukemia induction therapy should receive acyclovir antiviral prophylaxis (A-I). Annual influenza vaccination is recommended for all patients being treated for cancer (A-II). The optimal timing has not been established, but serologic responses may be best between chemotherapy cycles (more than seven days after the last treatment) or more than two weeks prior to the start of therapy (B-III). 

Colony-Stimulating Factors

Colony-stimulating factors are recommended for prophylaxis against neutropenia when the anticipated risk of fever and neutropenia is 20% or greater.

Prevention of Catheter-Related Bloodstream Infections

Hand hygiene, maximal sterile barrier precautions, and cutaneous antisepsis with chlorhexidine are recommended for all central venous catheter insertions (A-I). 

Hand Hygiene

Hand hygiene is the most effective means of preventing infection in the hospital (A-II).

Environment

HSCT recipients should be in private rooms (B-III). Patients with neutropenia do not need to be placed in single-patient rooms. Allogeneic HSCT recipients should be in rooms with more than 12 air exchanges, high-efficiency particulate absorption filtration, and positive pressure (A-III). Plants and dried or fresh flowers should not be allowed in the rooms of hospitalized neutropenic patients (B-III). 

Isolation and Barrier Precautions

No specific protective gear (gowns, gloves, or masks) are necessary during the routine care of neutropenic patients. Standard barrier precautions should be used for all patients when contact with body fluids is anticipated.

Food

In general, food should be well cooked. Well-cleaned uncooked fruits and vegetables are acceptable.

Skin and Oral Care

Daily showers are recommended to maintain skin integrity (expert opinion). Patients should brush their teeth two times per day or more with a regular toothbrush, and flossing can be performed if it can be performed without trauma (expert opinion). Patients with mucositis should rinse their mouths with sterile water, saline, or sodium bicarbonate rinses four to six times per day (expert opinion). Menstruating immunocompromised women should avoid tampons (expert opinion). Rectal thermometers, enemas, suppositories, and rectal examinations are contraindicated for patients with neutropenia (expert opinion).

This was a comprehensive guideline developed by the Infectious Diseases Society of America (IDSA) to guide clinicians in the care of patients with chemotherapy-induced neutropenia and in the management of febrile neutropenia. The full guide can be located at http://cid.oxfordjournals.org/content/52/4/e56.full.

To determine the effects of guided imagery training on quality of life (QOL) for survivors of breast cancer

Trained professionals facilitated five weekly live (LD) or teleconference (TD) group sessions. The initial four sessions each included four one-hour modules of training in guided imagery (i.e., four hours per week). Each module was divided equally between a didactic lesson and an interactive small group activity. Didactic lessons provided education on the mind-body connection, particularly the influence of mental imagery and corresponding sensory experiences on physiologic processes. Small group activities incorporated opportunities to process lessons and to practice active and targeted imagery aimed at improving QOL. Each week, participants were given a guided imagery CD to reinforce current lessons and to promote the practice of imagery techniques daily. The fifth week provided a final group check-in for individuals to share their future plans for incorporating imagery into daily life. Weekly calls were made to encourage daily practice during the intervention and for three months postintervention. Waitlist controls (WLs) received no intervention. Outcome measures were assessed before the behavioral intervention and at one and three months after the intervention.

• N = 118    
• MEAN AGE: 55.4 years (SD = 8.39 years) 
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Breast cancer survivors of all stages at least six weeks postcompletion of treatment
• OTHER KEY SAMPLE CHARACTERISTICS: Sample was an average of 50.9 (44.45) months from diagnosis.

• SITE: Multi-site    
• SETTING TYPE: Multiple settings    
• LOCATION: Anchorage and Seattle in community centers for group sessions and participants’ homes for daily practice of guided imagery

• PHASE OF CARE: Late effects and survivorship

Randomized, waitlist-controlled trial

• Functional Assessment of Cancer Therapy, Cognitive Scale (FACT-Cog) version 2
• Pittsburgh Sleep Quality Index (PSQI)
• Functional Assessment of Chronic Illness Therapy Fatigue scale (FACIT-F) version 4
• Medical Outcomes Study Short-Form survey (SF-36)
• Functional Assessment of Cancer Therapy, Breast (FACT-B)
• Functional Assessment of Chronic Illness Therapy, Spiritual Well-Being Expanded Scale (FACIT-Sp-Ex) version 4
• Brief Symptom Inventory-Global Severity Index (BSI-SI)

Both intervention groups (LD and TD) reported better cognitive function, less fatigue, and less sleep disturbance than waitlist controls (p < .01 for both). The LD and TD groups did not differ in any outcomes. No group effects were found for the other QOL outcomes. No time or group-by-time effects were found for any outcomes. A smaller portion of LD and TD participants reported clinically meaningful sleep disturbances (p < .01 for both) and fatigue (p < .05 for both) at the follow-up assessments.

After five weeks, the group guided imagery course provided by a trained facilitator may improve patient-reported cognitive impairment, sleep disturbances, and fatigue in breast cancer survivors. The delivery of this intervention in person or via teleconference produced the same results, suggesting that the intervention may be appropriate for use in telemedicine.

• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Findings not generalizable
• Intervention expensive, impractical, or training needs
• Other limitations/explanation: Participants were not blinded, and it is unclear whether the research assistants who did the QOL assessments were blinded to group assignment. The nonspecific effects of social support or attention may have been responsible for the improvement of symptoms given the lack of an active control group. The sample was mostly white and well-educated, limiting generalizability. The TD group was half the size of the LD group, limiting the study's ability to demonstrate a difference between these modes of delivery. The intervention would require training for facilitators to maintain fidelity; feasibility may be an issue in practice because of the time commitment required from facilitators and participants. Cognitive function was measured only with self-report instruments. The duration of the intervention effect is unknown because of the lack of long-term follow-up assessments.

A group guided imagery course, delivered live or via teleconference by a trained facilitator, may improve cognitive impairment, sleep disturbance, and fatigue for breast cancer survivors. However, more research with larger samples and a longer follow-up is warranted to determine whether the intervention is effective and practical.

To determine differences in toxicity and time spent with radiation-induced dermatitis during a course of conventional radiation therapy (RT) or intensity modulated RT (IMRT)

At the time of treatment, a physician and nurse prospectively evaluated the skin and recorded the maximum skin toxicity each week. Chi-square and Wilcoxon analysis was used to find differences between groups from retrospective data. Multivariate analysis determined significant predictors of grade 2 or higher radiation dermatitis

• The study sample was comprised of 804 cases of breast cancer.
• Of the cases, 405 were conventional RT and 399 were IMRT.

The study included cases treated at Fox Chase Cancer Center in Philadelphia, PA.

The study used a retrospective analysis design, using cases from 2001–2006.

• Dermatitis was graded using the Common Terminology Criteria for Adverse Events version 3.0 for acute radiation dermatitis: 0 (no change) to 5 (death).
• Breast size was grouped as small, medium, or large according to bra size.
• Additional variables included tumor stage, nodal stage, chest wall separation, breast radiation dose, total dose, use and timing of chemotherapy, and receiving tamoxifen.

In all breast size groupings, a significantly lower percentage of patients in the IMRT group developed grade 2 or higher radiation dermatitis (p ≤ 0.0004). Per group, volumes that developed a maximum toxicity of grade 2 or higher were 52% for IMRT and 75% for CRT. The time spent per week of radiation with grade 2 or 3 dermatitis was lower in the IMRT group. In the IMRT group, 18% of weeks were at grade 2 or 3, and in the conventional group, 71% of weeks were at grade 2 or 3. Weeks 2–6 for those receiving IMRT had significantly less toxicity (p < 0.00001). Predictors of grade 2 or greater dermatitis found to be significant (p < 0.021) were technique (e.g., use of IMRT), large bra size, treatment week, and chemotherapy or tamoxifen administered prior to or during radiation.

IMRT is associated with less skin toxicity than conventional RT.

• Not all IMRT cases were matched to appropriate controls in the conventional group.
• Some significant differences were noted among groups in breast size and proportion of patients who also received chemotherapy.
• No information was provided on any skin care regimen used.

To determine the incidence and severity of acute skin toxicity with IMRT compared to conventional RT

Women treated with breast conserving surgery and IMRT were matched one to one with historical controls based on bra size and chest wall separation. Maximum recorded skin toxicity during six weeks of RT was compared between the two groups using Chi-squared analysis or Fisher-exact tests. Cases were grouped for analysis by bra size.

• The study sample was comprised of 133 female cases, with 73 IMRT and 60 conventional historical controls cases.
• All patients had breast cancer in stage 0, I, or II.
• Breast dose ranged from 46–50 Gy, with a median of 46; the total dose ranged from 50–64 Gy, with a median of 60 in IMRT and 64 in conventional.

The study took place at Fox Chase Cancer Center.

The study used a prospective comparison with matched historical controls design.

Acute skin toxicity was scored using the National Cancer Institute (NCI) common terminology criteria (CTC) for acute radiation dermatitis by the physician or nurse weekly during treatment. Scores given to evaluate erythema were grade 1 for mild and grade two for moderate. Scores given for desquamation were grade 1 for dry and grade 2 or 3 for moist. Additional variables included in analysis were chest wall separation, total energy megavoltage, use and timing of chemotherapy, use and timing of tamoxifen, and tumor stage.

The degree of desquamation was greater for conventional patients (p = 0.0001). In the IMRT group, 21% had grade 2, compared to 38% in the RT group. Grade 1 desquamation was higher in the IMRT group (37% IMRT, 10% RT). No patient had grade 3 desquamation. There were no differences between the two groups in CTC or erythema scores. Subgroup analysis showed that the incidence and severity of desquamation by bra size was significantly lower in the IMRT group for small and large breast sizes (p < 0.04) but not for medium sizes. Use of IMRT (p = 0.0011) and breast size (p < 0.0001) were the only significant predictors for having moist desquamation.

IMRT was associated with reduced incidence and severity of desquamation.

Although CTV was found to be a significant predictive variable, it was not included in the stepwise regression analysis.

To evaluate the feasibility and efficacy of palliative radiation therapy given via static ports of tomotherapy

Tomotherapy is a treatment modality that delivers a series of highly modulated linear beam paths for hypofractionated palliative radiation therapy (RT). Doses given were 3 Gy in 10 fractions, 4 Gy in five fractions, or 8 Gy in one fraction. The selection of a schedule was individualized to patients. Pain was evaluated by physicians immediately before RT for current, worst within the past 24 hours, least, and average pain. Opioid consumption in the previous 24 hours was evaluated.

• N = 130
• MEDIAN AGE = 68 years (range = 36–89 years)
• MALES: 41%, FEMALES: 59%
• KEY DISEASE CHARACTERISTICS: Various tumor types were included with the most common being non-small cell lung, breast, and prostate cancers. All participants had painful bone metastases. The most common RT sites were the pelvis, lumbar region, and thoracic columns.
• OTHER KEY SAMPLE CHARACTERISTICS: In total, 64% of participants were receiving active antitumor treatment.

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

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

Prospective, observational study

• 11-point Numeric Rating Scale (NRS) for pain
• Pain response definitions were identified according to score reductions or increases by two points and by stable, increased, or decreased opioid consumption.

At two weeks, response rates ranged from 49%–55% with no significant difference between the fractionation groups. Among all patients, opioid consumption decreased (p < 0.001). At two months, response rates decreased to 40%. The rate of no response was highest in the 8 Gy single fraction group. This group also had increased opioid use and more frequent retreatment.

RT is effective for pain relief in patients with painful bone metastases. This study suggested that the TomoDirect™ delivery of RT can be feasible and effective.

• 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 
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Other limitations/explanation: No information regarding the use of bone modifying agents was given. Pain was assessed by physicians rather than patient-reported. Which pain scores were used for analysis was not clear.

RT was effective for pain reduction in patients with painful bone metastases; however, the duration of palliation may be brief. Studies have suggested that multiple fractionation for RT delivery may be more effective.

To test the effectiveness of the application of a mixture of turmeric and honey on treatment-induced oral mucositis in patients receiving chemotherapy and radiation therapy

Patients were randomly assigned to receive the mixture of turmeric and honey or to a control group that did not receive the intervention. The mixture was applied for five minutes before treatment and again five minutes after treatment. Study measures were obtained on days 2, 4, and 6 of treatment.

• N = 60
• AGE = 50% were between 50–60 years
• MALES: Not provided, FEMALES: Not provided
• KEY DISEASE CHARACTERISTICS: Not provided
• OTHER KEY SAMPLE CHARACTERISTICS: Fifty-five percent were rinsing their mouth after eating, 56.7% were using toothpaste, and 51.7% were brushing their teeth once a day.

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

• PHASE OF CARE: Active antitumor treatment

• Randomized, controlled trial

• World Health Organization Oral Mucositis Scale

The mucositis score was significantly lower at all post measurements in the experimental group (p < 0.05). Scores were similar between groups at baseline, but subsequent measures were lower in the experimental group.

The combination of turmeric and honey may provide some protection against the development of oral mucositis and may provide benefit for treatment.

• Small sample (< 100)
• Risk of bias (no blinding)
• Questionable protocol fidelity
• Not all patients were performing mouth care, and the differences in this aspect between groups is unknown. The method of randomization was not stated. Treatment and disease type information were not provided.

The results of this study suggest that turmeric and honey may have some promise in the management of oral mucositis, but this study has several substantial limitations. Further well-designed research is needed. One of the basic needs for preventing and managing oral mucositis is regular mouth care, the foundation of any intervention.

• This article reviewed the neurotransmitter and receptor systems involved with chemotherapy-induced nausea and vomiting (CINV) and a brief history of development of antiemetic therapies. CINV classifications was defined as follows.
  • Acute—occurring and resolving within 24 hours of chemotherapy
  • Delayed—occurring more than 24 hours after chemotherapy administration
  • Breakthrough—occurring despite antiemetic therapy
  • Refractory—unmanageable with current antiemetics
  • Anticipatory—conditioned response after prior inadequately controlled CINV.
• The article stated that anticipatory CINV is the most common kind.
• The article reviewed the mechanism of action and current knowledge regarding common antiemetic regimens and noted that given the physiology involved, optimal treatment requires a combination of therapies targeting multiple systems.

• Dexamethasone in combination with 5-HT₃ receptor antagonists is recommended (unless contraindicated or not tolerated). The author noted that this is too often not included.
• In delayed emesis, metoclopramide has been shown to be equivalent to ondansetron in controlling delayed CINV. Metoclopramide is also associated with extrapyramidal symptoms.
• Differences among 5-HT₃ receptor antagonists were noted.
  • Among first generation drugs, overall efficacy of the agents are similar.
  • Palonosetron is a second generation drug with a longer half-life, which appears to be associated with some preventive benefits.
  • Results of studies indicate that without some combination therapy, these drugs alone will fail in 40%–50% of patients.
  • The author noted that some individuals have a genetic tendency to metabolize these drugs differently and those with ultra-rapid metabolism have less therapeutic benefit. Palonosetron appears to have a smaller effect in this area.
• The effects of 2 mg per day of oral granisetron and 3.1 mg per day via epidermal patch appear to be similar.
• The addition of aprepitant (a neurokinin 1 [NK1] antagonist) to 5-HT₃ receptor antagonists and dexamethasone has demonstrated success. A larger benefit has been found for women than for men. The current approved regimen for aprepitant is a three-day regimen; however, ongoing studies are under way to determine if additional doses are helpful. When using aprepitant, the dexamethasone dosage should be reduced. A potential interaction between aprepitant and chemotherapeutic agents such as ifosfamide have been noted. In one study, the combination was associated with increased neurotoxicity.
• Olanzapine is an antipsychotic that blocks multiple neurotransmitters involved in CINV. Trials of olanzapine in combination with granisetron plus dexamethasone and palonosetron plus dexamethasone have demonstrated effectiveness in preventing CINV.

This article demonstrated the importance of combination therapy for prevention and management of CINV. The author provides a good overview of relevant physiology, mechanism of action of current agents, and current regimens used. The article points to the need for additional research with the use of olanzapine for CINV.