Participants in the treatment group received infusions of calcium gluconate and magnesium sulfate (1 g) before and after oxaliplatin. The chemotherapy protocol consisted of combination oxaliplatin, 5-fluourouracil (5-FU), and leucovorin. Three regimens of oxaliplatin were used: 85 mg/m² every two weeks, 100 mg/m² every two weeks, or 130 mg/m² every three weeks.

A total of 161 patients were enrolled in the study, with 96 placed in the treatment group and 65 in the control group.

The study had a retrospective design.

Toxicity was graded every one to two weeks by staff according to the National Cancer Institute's Common Terminology Criteria for Adverse Events and an oxaliplatin-specific neurotoxicity scale that assessed paresthesias.

Paresthesias, trismus, cramps, limb pain, and diarrhea were significantly less frequent in the treatment group. Pharyngolaryngeal dysesthesia were never reported in the treatment group versus 9% in the control group. In addition, less grade 3 toxicity was reported in the treatment group compared to the control group. At the end of oxaliplatin therapy, 65% of participants in the treatment group had no evidence of chemotherapy-induced peripheral neuropathy (CIPN) compared to 37% in the control group. By the end of treatment, 20% of patients in the treatment group showed evidence of CIPN versus 45% in the control group. Patients with grade 2 or 3 neurotoxicity at the end of treatment with oxaliplatin (85 mg/m²) recovered more rapidly from CIPN than those in the control group.

• The study was retrospective and not randomized or blinded.
• Staff who performed the assessments may have been biased in reporting.
• More patients who received either FOLFOX 4 or FOLFOX 6 regimens were included in the treatment group, making results more open to bias and placebo effect.

To compare the effectiveness of orally administered red morphine drops (RMD) and subcutaneous morphine (SCM) in patients with advanced lung cancer

Patients were randomized to two groups. Group 1 received oral RMD and a subcutaneous injection of isotonic saline. Group 2 received a placebo oral RMD and a subcutaneous injection of morphine. All injections were given in the leg in a location without edema. Patients were instructed to hold the RMD or placebo RMD solution in their mouths as long as possible before swallowing. The study preparations included a) morphine hydrochloride at 2 g, ethanol 96% at 5 g, cochenille tincture PhD.48 10 g, purified water up to 100 g (one drop corresponded to 0.6 mg morphine), b) ethanol 96% at 5 g, cochenille tincture PhD.48 10 g and purified water up to 100 g, c) injectable morphine 20 mg/ml, and d) isotonic saline. Measurements were taken at baseline and five, 10, 15, 20, 30, and 60 minutes after medication administration. Patients were not allowed to take any opioid within four hours prior to the experiment.

• N = 20  
• MEAN AGE = 69 years (range = 42–84 years)
• MALES: 10%, FEMALES: 90%
• KEY DISEASE CHARACTERISTICS: Lung cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Terminally ill patients receiving opioids for pain; resting dyspnea of at least 3 on 0–10 Visual Analog Scale at rest

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

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

Double-dummy randomized, controlled trial

• Visual Analog Scale (VAS) 0–10 to assess the severity of dyspnea
• Respiratory rate
• Oxygen saturation
• Pulse rate

There was no significant difference in dyspnea between the two groups. Both RMD and SCM showed a significant decrease in dyspnea (time p = 0.0451, and treatment p < 0.0001). In addition, RMD and SCM were associated with significant decreases in pulse rate (p = 0.0410). Although it was not statistically significant, patients receiving SCM showed a more rapid decline in dyspnea. Patients in the RMD group received 3.3%–8.6% of their total 24-hour opioid dose. Patients in the SCM group received 1.5%–5.5% of their total 24-hour opioid dose.

Both RMD and SCM improved dyspnea in terminally ill patients.

• Small sample (< 30)
• Baseline sample/group differences of import
• Risk of bias (no blinding)
• Key sample group differences that could influence results
• Other limitations/explanation: Primarily women in the sample; baseline dyspnea was 1 higher in the RMD group

RMD is a reasonable alternative to SCM and should be considered as part of patient preference at the end of life. Subcutaneous administration may provide more rapid relief. It is noteworthy that opioid use relieves dyspnea for patients receiving regular opioids for pain management. The most effective dosage of RMD is not yet known. Additional research to understand the pharmacokinetics of RMD is needed.

To assess the effects of psychosocial interventions on quality of life and mood symptoms in patients diagnosed with cancer within the past 12 months

• Databases searched, up to January 2011, were Cochrane Central Register, MEDLINE EMBASE, CINAHL, and PsycINFO.
• Authors provided an extensive listing of keywords and specific search strategies.
• To be included, studies had to
  • Be randomized controlled trials (RCTs) or quasi-RCTs involving interpersonal dialog between a trained helper and individual newly diagnosed patients with cancer.
  • Measure quality of life and general psychological distress.
  • Include control groups that received standard care only.
• Authors excluded trials involving a combination of psychosocial and pharmacologic interventions, as well as group- and couples-based interventions.

• A total of 3,272 references were retrieved.
• Quality evaluation used criteria specified in the review for random allocation and allocation concealment, blinding, loss to follow-up, and assessment of reporting bias.

• Authors chose 30 trials to include, with 20 included in the meta-analysis.
• The sample range across studies was 17–558, with a total sample across studies of 5,155.
• All studies involved patients diagnosed within the past 12 months only.
• Disease types included breast, colon, gastric, skin, prostate, and testicular cancers as well as, in some mixed trials, a few others.
• All participants were adult patients.

Multiple phases of care

• Anxiety outcomes were evaluated in four studies, depression outcomes were evaluated in six studies, and mood measures were evaluated in eight studies.
• Analysis of studies involving mood measures resulted in a standard mean difference (SMD) of –0.81 (95% CI, 1.44, –0.18, p = 0.01) in favor of the intervention.
• Analysis of quality-of-life outcomes showed mixed results with cognitive behavioral therapy, positive findings in favor of psychoeducational interventions (SMD = 0.29, 95% CI, 0.05, 0.54, p = 0.02), and no significant effects of counseling. Nurse-delivered interventions showed a significant positive effect (SMD = 0.23, 95% CI, 0.04, 0.43, p = 0.02) for quality of life. Interventions provided by a psychologist; general practitioner; and combined nurse, social worker, or others did not demonstrate significant effects.
• No meta-analysis addressed the outcomes of anxiety or depression only.
• Many studies were of relatively low quality, and the studies included substantial heterogeneity.

Findings suggest that psychosocial interventions have a positive impact on quality of life among newly diagnosed patients with cancer. Psychoeducational interventions and nurse-delivered interventions demonstrate a small significant effect across combined trials. Overall evidence does not indicate that individual psychosocial interventions are effective at improving the mood- and quality-of-life–related symptoms of patients newly diagnosed with cancer.

A small number of studies in meta-analysis related to mood changes. Effect sizes in mood changes were small, and study samples comprised high heterogeneity, demonstrating that findings should be interpreted with some caution in terms of clinical relevance.

The fact that nurse-delivered psychosocial interventions demonstrated a positive and statistically significant effect is promising, although the effect size was small. This finding provides some support for interventions delivered by nurses rather than by other healthcare professionals. Other studies have reported this finding. Nurses may be uniquely positioned to provide such interventions: Their knowledge base includes both physiologic and psychosocial components of the cancer experience, and individual interventions can simultaneously and effectively address physical and psychosocial symptom management. The findings of this study provide general support for the effectiveness of psychoeducational interventions.

The MEDLINE database was searched through June 2004 to identify experimental and quasiexperimental studies of exercise (cardiovascular and/or resistance training) during and following cancer treatment.

Twenty-six published studies, reflecting 18 experimental or quasiexperimental trials of exercise during cancer treatment and eight studies of exercise after cancer treatment, were identified. Of the 18 trials during treatment, 14 used some type of cardiovascular training; two used mixed training with cardiovascular, resistance, and flexibility exercise; and two applied a structured resistance training program. Of the eight trials of exercise after cancer treatment, all used cardiovascular or cardiovascular plus resistance training. The duration of the intervention ranged from two to 28 weeks, and the frequency of the exercise intervention ranged from daily to two times per week.

Outcomes were fatigue, health-related quality of life, symptom distress, psychological distress, body composition, physical exercise capacity (maximal oxygen consumption), immunologic parameters, and muscle strength. Treatment evaluated cardiovascular and/or resistance exercise.

• Most of the studies were conducted in women with breast cancer or in samples with mixed solid tumors; single studies in patients with prostate cancer, colorectal cancer, and hematologic malignancies were noted.
• Sample sizes ranged from five to 155 participants.
• Average participant age ranged from 19 to 77 years.

Five of 18 studies of exercise during cancer treatment specifically found improvements in fatigue, and most of these studies were in women with breast cancer. Of note, a trial of resistance training three times per week in men with prostate cancer undergoing androgen depletion therapy showed improvements in fatigue after a 12-week program. Of the eight studies of exercise following cancer treatment, none reported statistically significant improvements in fatigue, but there were improvements in functional status, quality of life, psychological distress, strength, and capacity.

Although recent evidence supports the use of resistance exercise during cancer management as an exercise mode to counteract adverse effects of the disease and treatment, most of the studies were conducted using cardiovascular training. Promising results in terms of fatigue and other outcomes of a short-term resistance exercise program on patients diagnosed with prostate cancer and undertaking androgen-depletion therapy have been reported.

To evaluate the effectiveness of a the telehealth-delivered exercise intervention on symptoms among breast cancer survivors

Patients were randomized to the telehealth intervention or usual care. After baseline assessment, those in the study group received instructions on how to access the private area of the system. The intervention consisted of three sessions per week of exercise following recommendations of the American College of Sports Medicine for cancer survivors. Each session was delivered online. The system allowed participants to send messages and set up video conferencing, participants to write questions or comments, and research staff to comment and monitor performance remotely. Participants received phone calls from research staff if needed. The intervention lasted eight weeks. Usual care patients received basic written recommendations for exercise. After six months, they were offered the opportunity to participate in the telehealth program. Assessments were done at baseline, at completion, and at six months.

• N = 72   
• MEAN AGE = 48.3 years
• FEMALES: 100%
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: All had breast cancer and previous surgery. Most also had previous radiotherapy and chemotherapy.
• OTHER KEY SAMPLE CHARACTERISTICS: Most had surgery within the last 12 months.

• SITE: Single site   
• SETTING TYPE: Home    
• LOCATION: Spain

• PHASE OF CARE: Late effects and survivorship

• Randomized, controlled trial

• EORTC Cancer Core Quality of Life (EORTC QLQ-C30) and EORTC Breast Cancer Quality of Life (QLQ-BR23)
• Brief Pain Inventory (BPI)
• Handgrip strength
• Isometric abdominal and back strength 
• Sit-to-stand test for lower body strength
• Piper Fatigue Scale (PFS)

After the intervention, the telehealth group reported lower pain severity (p = 0.001) and interference (p = 0.045). The telehealth group reported improved total fatigue perception compared to controls (p = 0.001). This improvement was maintained at the six month follow-up (ES d = –0.75, p = 0.002). Adherence rate for exercise sessions was 93.9%. Muscle strength and quality of life (QOL) were also improved in the telehealth group compared to controls. There were no technical issues or adverse effects of the intervention observed.

An online exercise and interaction approach was effective in reducing pain and fatigue and improving QOL and muscle strength. The program had good patient adherence.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Intervention was expensive and impractical, or training needs existed.
• Baseline pain and type of pain are not reported.  
• Baseline fatigue was lower among the intervention group.
• Authors noted that a large number of staff were involved in the provision of this program, which may limit the ability to sustain this type of program.

The online delivery of an interactive exercise intervention was shown to be effective. An Internet-based intervention may be a useful alternative to traditional approaches to deliver such interventions, particularly in the setting of barriers such as distance and time. The comparative costs for staff time to deliver and maintain this type of intervention need to be evaluated.

The objective of this study was to investigate whether a handheld fan reduces the sensation of breathlessness in patients with dyspnea.

Room temperature and humidity were controlled, and the fan was directed to either face or leg for five minutes. This was followed by a 10-minute washout followed by repeat intervention, as crossover dyspnea scores were collected at baseline, at completion of each 5-minute intervention, and after 10-minute washout of each intervention. Additional data collected included pulse rate and oxygen saturation after each 5-minute use of the fan and each 10-minute washout.

• The study reported on a sample of 49 participants.
• The mean age was 71.3 years, with a range of 33–90 years.
• Of the sample, 27 were females and 23 were males.
• Diagnoses included chronic obstructive pulmonary disease (26), lung cancer (primary or secondary) (11), asthma (8), heart disease (15), bronchiectasis (7), pneumonitis (4), other (20), and multiple diagnoses (26).
• Other key characteristics included patients in the United Kingdom with refractory breathlessness.
• Patients were permitted to be on opioids, corticosteroids, and sedatives.
• Exclusion criteria included use of continuous or short-burst oxygen during the study period and hemoglobin less than 10 gm/dl.

The study was conducted in an inpatient medical center and a hospice setting in the United Kingdom.

• Patients were undergoing end-of-life and palliative care.
• The study has clinical applicability for late effects and survivorship.

The study had a randomized, controlled, crossover design.

Visual analogue scale (VAS) 10 cm for dyspnea was used. Anchors were no shortness of breath to worst shortness of breath. VAS calculations were performed by a noninvestigator.

Only eight participants perceived benefits of the fan to the face at the conclusion of 5 minutes, but 19 participants perceived benefit at the end of the 10-minute washout. The eight who initially perceived benefit did register reduction in benefit during the washout period. A significant difference in VAS scores was seen between the two treatment arms with reduction in breathlessness when the fan was directed to the face (p = 0.003).

Use of a fan pointed at the face may reduce the sensation of breathlessness in a controlled temperature and humidity environment.

• Washout period of 10 minutes did not appear adequate because the benefit of the fan on the face for some resulted in sustained reduction of dyspnea at the end of 10 minutes. Because washout time may have been incomplete, the results of the second arm of the study may have been biased, and no actual control period in the study existed. 
• The study had a relatively small sample size of less than 100.
• Results were found with temperature and humidity control, not just fan use.

Handheld fans are inexpensive and easy and permit empowerment of patient initiation of symptom management. This study suggests that this intervention, in a controlled temperature and humidity condition, will decrease the sensation of dyspnea. Patients may continue to experience benefit from the intervention even after its discontinuation, so it may be extremely helpful as bridge management when awaiting onset of an intervention such as a pharmacologic agent.

To establish feasibility of studying the effects of yoga on function, pain, and quality of life in women with aromatase inhibitor–associated arthralgias

Women who had joint pain attributed to aromatase inhibitor treatment were studied. Patients met two times per week for eight weeks for yoga sessions taught by certified instructors. The protocol used was inspired by Iyengar yoga involving precise postures, and meditation using relaxation and combinations of static and active stretching and isometric and dyunamic strengthening. Sessions were done among groups of 5–10 women, and an abbreviated version was given for home practice during week 2. Patients were asked to perform home practice for 15 minutes three times per week on days when sessions did not take place. Study assessments were done at baseline and at the end of the program.

• The study reported on 10 female patients.
• Median patient age was 58 years, with a range of 50–71 years.
• All patients had breast cancer and joint pain,  were post-menopausal, and in active treatment with aromostase inhibitors.
• Of the sample, 90% were Caucasian, 40% were employed, and 60% had at least college-level education.

• Multisite
• Outpatient setting
• New Jersey

Patients were undergoing active antitumor treatment.

This was a quasi-experimental feasibility study.

• Functional reach and sit and reach testing
• Self-reported Patient Specific Functional Scale
• Functional Assessment of Cancer Therapy–Breast (FACT-B)
• Brief Pain Inventory (BPI)

Of the sample, 80% reported adherence to home practice as recommended. Participants had significant improvement in functional reach (p = 0.048) and sit and reach (p = 0.009). Participants experienced significant reduction in pain severity (3.9–2.79, p = 0.016).

The yoga protocol used here was associated with improvement in flexibility and pain associated with aromatase inhibitor–induced arthralgia.

• The study had a small sample, with less than 30 participants.
• The study had risk of bias due to no control group, no blinding, and no random assignment, and due to sample characteristics.
• Findings are not generalizable.
• Effects were related to arthralgia-related function and pain only.

There is limited evidence regarding interventions to reduce arthralgia pain in patients undergoing cancer treatment. This study shows that a yoga intervention is feasible and may provide some promising results. Further research in this area is warranted.

To evaluate the feasibility of tai chi to improve well-being for women with breast cancer treatment-associated arthralgia

Women met twice weekly for eight weeks for group tai chi under supervision. The program was a gentle, low-impact form of tai chi focusing on body awareness, deep breathing, and weight bearing. Women were provided written information for home practice. Participants were asked to complete journal entries after each tai chi session and home exercise, encouraged to maintain usual activities, and asked to refrain from other exercise during the study. Study measures were obtained at baseline and at the end of 8 weeks.

• N = 12  
• MEAN AGE = 59 years (range = 49-76 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All had completed initial breast cancer treatment and were post-menopausal, currently free of disease, and on aromatase inhibitors.  
• OTHER KEY SAMPLE CHARACTERISTICS: 91.6% were white, one-third were employed full-time, and 58% had some college education.

• SITE: Single site
• SETTING TYPE: Outpatient   
• LOCATION: New Jersey

PHASE OF CARE: Late effects and survivorship

Single-group observational, mixed-method, feasibility

• Functional Assessment of Cancer Therapy–Breast (FACT-B)
• Brief Pain Inventory
• Hospital Anxiety and Depression Scale (HADS)
• Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-fatigue)
• Qualitative analysis of journal entries

There was a reduction in anxiety from 8.0 to 5.7 (p = .003) and in depression from 5.17 to 2.42 (p = .02). A positive, but non significant, reduction in fatigue and pain occurred. Themes from analysis of qualitative results were improved relaxation and reduced stress, an increase in undisturbed sleep, and perceived value from the group and instructor support. There were no adverse events.

Tai chi participation appears to be feasible for breast cancer survivors and may have positive effects on anxiety and other symptoms.

• Small sample (< 30)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Risk of bias (no appropriate attentional control condition) 
• Risk of bias (sample characteristics)
• Other limitations/explanation: Adherence to sessions is not reported. Sample was limited to women on aromatase inhibitors experiencing pain from arthralgia.

Tai chi sessions are feasible for cancer survivors and may be of benefit. This combination of relaxation and exercise disciplines may be helpful and acceptable to some patients. Study findings here suggest that the supportive nature of instructor-led group sessions contributed to the positive results.

The study was conducted to investigate the clinical improvement observed in patients with advanced cancer and hypoactive delirium after the administration of methylphenidate hydrochloride (MPH).

First, a 10 mg test dose of MPH was given orally to all participants. If there were no distressing side effects, participants were given 10 mg of MPH twice daily at 8 am and 12 pm. Follow-up was daily for hospital inpatients and every three to four days for patients in the community. Doses of MPH were increased in 5 mg increments to reach the maximum tolerable dose for the patient’s satisfaction and the resolution of delirium.

Measurements were taken before delirium and delusions (T0), at baseline prior to the MPH treatment (T1), one hour after after the MPH dose (T2), and when a stable dose was achieved (T3). 

The Mini-Mental State Examination was used as an assessment tool on a daily basis for inpatients and every three to four days for outpatients.

• All participants had a diagnosis of advanced metastatic cancer. Participants had lung, colon, breast, prostate, cervical, or testicular cancer. 
• The total number of participants was 14.
• Participants were between the ages of 41–80 years.
• 64% of participants were male and 36% were female.

The study utilized a case series design for patients with advanced cancer and hypoactive delirium.

• The Mini-Mental State Examination (MMSE) measured global cognitive function.
• No specific information was provided on the instruments used to assess psychomotor retardation, sleep and drowsiness, absence of delusions, or absence of delirium.

All participants had a positive response to MPH that included increased alertness, partial-to-complete resolution of psychomotor retardation, normalization of slurred speech, and a marked increase in energy levels.

All 14 participants showed improvement in their cognitive function as documented by the MMSE. In 13 patients, the median MMSE score improved to 28 (mean = 27.8, standard deviation = 2.4, p = 0.02) compared with the median score one hour after the first dose of MPH. One patient died before reaching a stable dose of MPH.

The pretreatment MMSE median score was 21 (mean = 20.9, standard deviation = 4.9), which improved to a median of 27 (mean = 24.9, standard deviation = 4.7) after the first dose of MPH (p < 0.001).

MPH improved alertness and general cognitive function in a small sample of patients with advanced cancer. However, due to confounding issues with disease and treatment responses, more research is warranted to determine its effectiveness.

• The study had a small sample size.
• The study was limited to patients with advanced cancer.
• All participants received MPH, so there was no control group.
• The study had a limited measurement of cognitive function, as the MMSE is a global indicator with known practice effects.
• The study did not explain its assessment of psychomotor functioning or its determination of sleep and drowsiness.
• There were confounding issues with brain metastases in 29% of participants.
• There were confounding issues with pain medications in 57% of patients.
• There was no discussion regarding the clinical significance of the changes in MMSE scores.

To evaluate the degree to which a multi-component rehabilitation program improves symptom control and quality of life in patients with advanced cancer

The intervention was a 10-12 week program offered by a multidisciplinary team, consisting of nutritional counseling, a collaborative care plan based on patient goals, a palliative care physician specialist focused on symptom-related medical interventions, a pivot nurse for care coordination and case management, and an exercise component with semi-weekly exercise sessions with a physical therapist and a home exercise plan. Occupational therapy was provided and focused on self care, leisure, and productivity. Patients were assessed at baseline and during their final clinic visit at the end of the study.

• N = 131  
• MEAN AGE = 59.9 years (SD = 13.0 years)
• MALES: 50.4%, FEMALES: 49.6%
• KEY DISEASE CHARACTERISTICS: All had stage III and IV disease with a variety of primary tumor types including both hematologic and sold tumors.
• OTHER KEY SAMPLE CHARACTERISTICS: 38% were on current chemotherapy; most had ECOG performance status of 1 or 2.

SITE: Single site  

SETTING TYPE: Outpatient  

LOCATION: McGill University Cancer Center, Montreal, Canada

Quasi-experimental

Change in symptom severity was analyzed and Cohen’s d was used to calculate effect size. Severity of depression from ESAS declined (p <. 0001, d = 0.7); anorexia declined (p < .0001, d = .4);  pain declined (p < .0001, d = .4); physical and general fatigue declined (p < .0001, d = .7); mental fatigue declined (p < .0005, d = .4); and level of distress and difficulty coping declined (p < .0001).

The multi-component rehabilitation program provided here resulted in a significant improvement in multiple symptoms and a reduction in distress and difficulty coping.

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment) 
• Risk of bias (no appropriate attentional control condition)  
• Unintended interventions or applicable interventions not described that would influence results
• Subject withdrawals ≥ 10%
• Other limitations/explanation: 30% of patients withdrew from the study–the majority of these were due to death or disease progression. No information is provided about medication changes over the course of the study that might affect outcomes measured. The report states some different results in the body of the article versus tables provided.

A multi-component, multi-disciplinary rehabilitation and palliative care program can provide effective improvement of multiple symptoms in patients with advanced disease.