Evaluate effectiveness of pyridoxine for treating PPE in patients with metastatic colon cancer who are receiving continuous 5-FU

Patients were treated with 5-FU 200 mg/m² by continuous infusion (CI) until moderate to severe toxicity developed.

Five previously untreated patients who developed PPE were given oral pyridoxine (50 or 150 mg every day) when moderate PPE changes were noted.

Study conducted between September 1984 and July 1986.

N: 25

KEY DISEASE CHARACTERISTICS: Patients with metastatic colon cancer receiving continuous 5-FU infusion (200–300 mg/m²/day).

SITE: Multi-site

LOCATION: University of Kansas Medical Center; Fred Hutchinson Cancer Research Center

• Non-randomized, non–double-blinded, uncontrolled study

Skin toxicity was graded as follows.

• 0 = Normal
• 1 = Numbness, nail changes, painless swelling, or erythema
• 2 = Painful erythema with or without swelling
• 3 = Moist desquamation

PPE developed in 16 of the 25 patients. The five previously untreated patients who developed PPE received 50 or 150 mg of oral pyridoxine per day when moderate PPE changes were noted. Reversal of PPE without interruption of 5-FU was seen in four out of five patients, and these patients continued 5-FU for a median of six months after developing PPE.

Oral pyridoxine may reduce incidence and severity of PPE symptoms associated with 5-FU continuous infusion.

• Small sample size
• Not randomized and not double-blinded
• Inadequate description of measurement tool/method to grade PPE symptoms

To test the efficacy and safety of two different schedules of ondansetron as rescue antiemetic treatment in patients who were refractory to standard antiemetic prophylaxis for delayed emesis following moderately emetogenic chemotherapy (MEC)

Patients were randomly allocated to one of two treatment groups for rescue antiemetic treatment: intramuscular ondansetron 8 mg or oral ondansetron 16 mg for days two to six (antiemetic prophylaxis was provided by ondansetron 8 mg IV plus dexamethasone 8 mg IV for acute emesis and dexamethasone 8 mg for four days for delayed emesis).

• The sample consisted of 89 participants.
• In the intramuscular ondansetrong group, the average patient age was 58 years with a range of 27–83 years. In the oral ondansetron group, the average age was 61 years with a range of 28–79).
• The sample was 85.4% female and 14.6% male.
• The majority had breast, lung, and gynecologic cancers.
• Patients received either an anthracycline chemotherapy regimen (highly emetogenic chemotherapy [HEC], MEC), a carboplatin regimen, or an irinotecan/oxaliplatin regimen.

The study was conducted at a single site, outpatient setting.

All patients were in active treatment.

The study design was a prospective trial (open label, phase II, randomly assigned to treatment group).

• Participants recorded in diaries the dates and times of emetic episodes, severity of nausea or vomiting, use of rescue treatment, and efficacy of treatment (absence or presence of further emetic events).
• Participants also rated their personal satisfaction with the assigned rescue medication (satisfied, partially satisfied, unsatisfied).
• The Common Terminology Criteria for Adverse Events (NCI-CTCAE. V. 3.0) was used.

Oral ondansetron 16 mg was significantly superior to intramuscular ondansetron 8 mg for nausea and vomiting control during days two to six (p < 0.01). The two arms had a similar adverse event profile. A higher degree of personal satisfaction was found with oral ondansetron.

Because of its high efficacy and excellent tolerability, oral ondansetron is an important option in the management of MEC-related delayed emesis refractory to standard antiemetic prophylaxis.

• The sample was small with fewer than 100 participants.
• No control group was included.
• The frequency of the use of rescue medication was not reported, which may have contributed to the study results (ease of access to phone orders may have contributed to better efficacy and more satisfaction.)
• Interpretation of results as a pure difference between orodispersible ondansetron and intramuscular ondansetron is difficult.

The oral form of ondansetron could provide satisfactory rescue for breakthrough delayed emesis when compared to the Intramuscular form of ondansetron, with a similar adverse event profile.

Patients were randomly assigned to the control group (usual antiemetic protocol) or experimental group (usual antiemetic protocol plus music intervention during the 48 hours of high-dose cyclophosphamide administered as part of the preparative regimen for autologous or allogeneic bone marrow transplantation). The experimental group listened to self-selected music (by portable compact disc players and headphones) for 45 minutes at 6, 9, and 12 hours after the start of each infusion as an adjunct to antiemetic therapy.

• The sample consisted of 39 patients, but 33 were included in data analysis.
• The experimental group had 11 males and 5 females; the control group had 8 males and 9 females.
• The median age was 40.3 years for males and 36.9 years for females.
• Race and ethnicity were not reported.
• Treatment was autologous or allogeneic bone marrow transplantation, with high-dose preparative regimens. Participants were inpatients.

The study was conducted at a comprehensive cancer center in the midwestern United States.

The study design was a randomized, controlled clinical trial.

• Nausea was measured at baseline and every eight hours using a visual analog scale (VAS) in the form of a thermometer (0–100 in five-degree increments).
• Nausea was measured the with “feel bad” scale, a five-point, Likert-type scale describing how bad the nausea felt or how sick to the stomach the patient was. Subjective feelings of nausea and all episodes of vomiting were recorded.

Significant differences were found between scores on the VAS for nausea and number of episodes of vomiting; less nausea and fewer instances of vomiting were reported in the experimental group.

Music as an adjunct to antiemetic therapy for chemotherapy-induced nausea and vomiting with high-dose chemotherapy can be effective.

• Only bone marrow transplant recipients were included, one site was used, and the sample size was small.
• The study was a longitudinal study; therefore, problems existed with multiple data collection points, resulting in some missing data.
• Compliance issues existed regarding the music intervention. Patients did not always want to listen to music at designated times because they did not feel well or visitors were present.

• FINAL NUMBER STUDIES INCLUDED = 6
• TOTAL PATIENTS INCLUDED IN REVIEW = 208
• KEY SAMPLE CHARACTERISTICS: All trials included MLD with some form of compression. These were placed into three categories, (a) MLD with standard physiotherapy versus standard physiotherapy, (b) MLD with compression bandaging versus compression bandaging, or (c) MLD with compression therapy versus nonmanual lymphatic drainage treatment with compression therapy 

PHASE OF CARE: Late effects and survivorship

1. MLD with standard physiotherapy versus physiotherapy: This method demonstrated improvements in both groups, but no significant differences were seen between the two.
2. MLD with compression bandaging versus compression bandaging alone: A significant percentage in reductions were seen for bandaging alone with an additional 7.11% reduction with MLD. Significant analyses showed that participants with mild to moderate BCRL responded better to MLD than participants with more severe swelling.
3. MLD with compression therapy versus nonmanual lymphatic drainage treatment with compression therapy: Too varied

1. Volumetric changes in arm, hand, or trunk indicated that more research should be done to identify the most clinically meaningful volumetric measurement.
2. The functional outcome of range of motion showed contradictory results.
3. Quality of life outcomes were inconclusive or not measured in all, and in two trials that measured this outcome, one did not report the results. Future research should use a lymphedema-specific quality of life tool.

• MLD is safe and may offer an additional benefit to bandaging for fluid reduction.
• More studies are needed to confirm which stage of lymphedema benefits most from the addition of MLD.
• Studies should include a lymphedema-specific quality of life tool and functional outcomes.

• Trials were limited in size and participants
• Potential bias in four trials as person measuring swelling knew what treatment participants were receiving
• All trials assessed phase 1 decongestion, but only one also looked at phase 2 maintenance.

Nurses need to provide early identification and education to affect patients' lymphedema treatment. MLD is a safe component of lymphedema therapy. Long-term adherence to treatment and garments are needed maintain reductions in swelling.

Database searched was MEDLINE (1966-Dec 2003).

Search keywords were acupuncture, alternative medicine, electroacupuncture, moxibustion, “injections, intramuscular”, “Medicine, Traditional Chinese”, acupressure, transcutaneous electrical nerve stimulation (TENS), and TENS. These were combined with nausea, vomiting, emesis, antiemetic therapy, and antineoplastic agents/adverse effects.

Studies were included in the review if they

• Were randomized.
• Involved patients receiving chemotherapy.
• Included an intervention that stimulated acupuncture points.
• Reported on nausea or vomiting as outcomes.

Studies were excluded from the review if they had a high possibility of bias.

In all, 14 studies were identified and reviewed.

In the nine studies that evaluated acute vomiting management via acupuncture-point stimulation, acute vomiting was reduced but nausea severity was not.

In the seven studies that assessed acute nausea via acupressure, acute nausea severity was reduced.

Three studies that evaluated delayed vomiting did not support the intervention.

In the five studies using acupuncture-point stimulation, the intervention did not reduce delayed vomiting.

The pooled results of 11 studies using acupuncture-point stimulation plus antiemetics for chemotherapy-induced nausea and vomiting (CINV) showed significant reduction in acute vomiting and marginal statistical significance for reducing acute nausea.

Electroacupuncture provided protective effects for acute vomiting, but acupuncture did not. Acupressure was effective for acute nausea in patients using “state-of-the-art” antiemetics. However, placebo effects may have influenced results.

To determine the feasibility and acceptability of mindfulness-based stress reduction to manage the symptoms of fatigue, anxiety, and depression in women with metastatic breast cancer

An eight-week mindfulness-based (Kabat Zinn) stress reduction course was taught by a trained, experienced instructor. The sessions in weeks 1 and 8 were two and a half hours, and week 2–7 sessions were two hours. Week 6 included a day of mindfulness of four and a half hours. Home practice with CDs 30 minutes a day was recommended. Sessions were done in a group setting.

• N = 19  
• AGE RANGE = 37–65 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Metastatic breast cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Mean years since metastatic breast cancer diagnosis was 2.76; Eastern Cooperative Oncology Group (ECOG) Performance scores 0–2; stable disease; life expectancy at least six months

• SITE: Single site  
• SETTING TYPE: Outpatient    
• LOCATION: Community oncology center, United Kingdom

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

Mixed method design using qualitative and quantitative data with repeated measures

Qualitative data consisted of interviews one to two weeks prior to the course and four months after the course. Quantitative data consisted of four questionnaires delivered at five time points: the Brief Fatigue Inventory (BFI), the Hospital Anxiety and Depression Scale (HADS), the EuroQol Quality of Life-5 Dimensions, and the Toronto Mindfulness Scale (TMS) at baseline and at weeks 4, 8, 15, and 24. Quantitative data consisted of one questionnaire at two time points: the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C30) at baseline and at week 24.

A group mindfulness-based stress reduction intervention appeared feasible for patients with stable advanced cancer. However, the intervention as used here was time intensive. This type of intervention may be helpful in dealing with some symptoms in patients with advanced disease.

• Small sample (< 30)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Intervention expensive, impractical, or training needs
• Other limitations/explanation: Cost to train mindfulness instructors; time commitment for patients; repeated measures design raises the question of potential testing effect as the same instruments were used repeatedly; no control comparison or attention control study design, so it is impossible to tell how much of the changes seen in anxiety and depression were due to the group interaction rather than the intervention

There is an opportunity to study mindfulness-based stress reduction in patients with metastatic breast cancer and other patients with advanced disease. This study showed that this may be feasible; however, recruitment was difficult, and patients identified barriers related to severity of illness, time commitment, and travel to attend sessions.

To investigate the impact of Pilates exercise on physical parameters, as well as on fatigue, depression and quality of life among women with breast cancer.

Patients selected for participation were randomly assigned to a home exercise program or to the hospital exercise program. Those in the hospital program performed Pilates exercise for one hour per day three times a week for eight weeks. All patients were given an instructional booklet showing pictures of the exercise program as well as information about lymphedema prevention and activities of daily living. All patients were instructed to perform these exercises once daily at home and to walking 20 to 30 minutes per day, three days a week. Assessments were performed prior to the intervention and eight weeks after the exercise program.

• The sample was comprised of 42 participants.
• Mean age was 49.13 years.
• All participants were female.
• Of the participants, 98% had a total mastectomy.
• There was an average of 38 months since diagnosis of breast cancer.
• All patients had completed treatment.
• Forty percent had adjuvant treatment.

• Single site
• Outpatient
• Turkey

The phase of care was late effects and survivorship.

This was a prospective, randomized two-group, pre-/post study.

• Six-minute walk test
• Modified sit-and-reach test (for flexibility)
• Brief Fatigue Inventory (BFI)
• Beck Depression Inventory (BDI)
• European Organization for Research and Treatment of Cancer QOL scale (EORTC) quality of life QOL scale
   

• Almost 50% of the initial sample assigned to home exercise failed to complete the study due to lack of interest, difficulty commuting to the hospital, or medical problems.
• The hospital exercise group showed significant improvement in the six-minute walk test (p = 0.00), depression scores (p = 0.01), and functional aspects on the QOL scale (p = 0.04).
• The only difference between groups was seen in the six-minute walk test, with hospital exercise patients showing improvement and others showing a decline.

Supervised Pilates exercise appears to have positive effects on depression and physical functioning. There was no effect seen on fatigue. A substantial number of those on a home exercise program failed to complete the study, and findings and comparisons are limited by the small sample size.

• The study had a small sample size, with less than 100 participants.
• Baseline sample/group differences were of import.
• The study had risks of bias due to no control group, no blinding, no appropriate attentional control condition, and the sample characteristics.
• The intervention was expensive, impractical, and required training.
• Only women with breast cancer were studied, so findings may not apply to other types of patients. The home exercise intervention was not well described, and apparently consisted of just the booklet and a recommendation to do exercises. The fact that so many patients in the home exercise did not complete the study raises the question of the practicality and ability to maintain patient interest in this approach. Patients in the hospital exercise group had higher baseline fatigue and depression scores and may have had greater opportunity for improvement. Patients in the hospital exercise group did this in a group setting; related social support may have influenced results.

This study provides some evidence that exercise can be of benefit to patients in managing depression. The study has multiple limitations.

To evaluate the protective effects of Na-sucrose octasulfate (NaSOS) on radiation-induced skin damage in patients with head and neck cancer.

Each patient was his or her own control. NaSOS was applied on one side, and the placebo was applied to the other. It was started on day 1 of radiation therapy (RT) treatment. The gel was applied twice a day during RT and for two weeks after.
 

• The sample was comprised of 60 patients (20 females, 40 males).
• Mean age was 60 years (range 21–81).
• Patients had head and neck cancer.
• Megavoltage was 4 to 6 MV.
• There were two opposing lateral portals with separate anterior low neck portals, 2 Gy per fraction, to a total dose of 50 to 70 Gy. Mean total dose was 59.7 Gy.

Norway

The study used a quasiexperimental, double-blind, vehicle-controlled design. Each patient was his or her own control.

• Assessments were performed at initiation and weekly.
• European Organisation for Research and Treatment of cancer (EORTC)/Radiation Therapy Oncology Group (RTOG) acute skin reaction scoring system was used for skin reactions and for pain and itching on both sides.

• The mean skin reaction grade was higher where the placebo was used (p = 0.02).
• There were no differences between groups in other variables or the timing of skin reaction development.
   

There was no significant protective effect with use of NaSOS.

• The authors did not specify who performed evaluations, and there was no interrater reliability.
• There was no log for validation of compliance with study protocol.
• Other skin care regimens are uncertain.
• The study had a relatively small sample size.

STUDY PURPOSE: To review findings of 10 systematic reviews of clinical trials of erythropoietic-stimulating agents (ESAs) in the five-year period spanning 2004–2008.

TYPE OF STUDY: Systematic review

TOTAL REFERENCES RETRIEVED: 10

• FINAL NUMBER OF STUDIES INCLUDED = 10
• TOTAL PATIENTS INCLUDED IN REVIEW =  86,374
• SAMPLE RANGE ACROSS STUDIES: 1,949–21,378
• KEY SAMPLE CHARACTERISTICS: Inference that all patients included in reviews were patients with cancer, but report did not actually specify

PHASE OF CARE: Active treatment

10 reviews of effects of ESA treatment on symptoms and quality of life (QOL) were reviewed.

• (From authors) Overall evidence from studies seem to support  a symptom and QOL benefit from ESA treatment, which is unlikely to be due to chance alone.
• (From reviewer) Quality of studies presented in review, variability of instruments and ESAs used to measure variables of interest, missing data, and lack of description of sample populations in studies limits sufficient evidence for empirical benefit from ESA treatment in patients with cancer

• Focus of review was on patient-reported symptoms and QOL outcomes versus all risks (safety, survival, thrombosis) and benefits (transfusion use, hematologic response) of ESA use.
• Not all of the studies reviewed were placebo controlled or double blinded.
• Increased risk of placebo effect when outcome of interest is patient self-report.
• Many studies failed to report metrics needed for a more detailed analysis.
• Substantial loss of data and lack of documentation of how missing data were handled.
• Timing and conditions under which symptoms and QOL were measured were not described in many studies.

• Focus future studies on description of conditions for the safe use of ESAs.
• Determine empirically derived cutoff above which ESA therapy is contraindicated.
• Conduct detailed analysis of secondary data sources (meta-analysis).
• Need for inclusion of patient perspective of benefits and harms of ESA therapy.
• Development of patient education materials about relative risks and benefits of ESA use or lack thereof.

Patient were randomized to receive sucralfate or placebo, delivered in an oral suspension with identical appearance, taste, and consistency. Patients received six 1-gram doses daily at regular intervals beginning on day one of radiation therapy (RT) and throughout RT, including weekends.

• The study reported on 44 patients with head and neck cancer; 23 received sucralfate and 21 received placebo.
• Mean age of the sample was 55 years with a range of 34–72 years.
• Patients were receiving RT covering at least one-third of the oral mucosa to a minimum dose of 60 Gy.
• Patients were not receiving chemotherapy.

The study was conducted between December 1996 and December 1997.

This was a prospective, randomized, double-blind, placebo-controlled trial.

• Patients received baseline oral examinations and questionnaires with drug- and oral mucositis-related questions.
• The Vander Schueren et al. scoring system was used to assess for mucositis.
• World Health Organization (WHO) criteria for oral and topical analgesics were used.
• Patients underwent biopsy on the 20th day of RT.

• Compliance in the sucralfate group ranged from 3–6 times per day with a median of 5. Patients in the placebo group had a 4–6 times per day compliance rate with a median of 5 (p = 0.21).
• Mean mucositis scores on the 20th day of RT were 2 in the sucralfate group versus 4 in the placebo group (p = 0.0002).
• Pain and dysphagia were reported less frequently in the sucralfate group, but the difference was not significant.
• Patients in the sucralfate group had decreased altered vascular calibration, altered vascular permeability, and leukocyte emigration.

Sucralfate is low in cost, is easily administered, and had a similar compliance rate.

• The sample size was small.
• Compliance rates raise questions.