• Cohort A: Six patients received docetaxel (43 mg/m²) weekly for six weeks every eight weeks.
• Cohort B: Six patients received docetaxel weekly combined with etanercept (25 mg subcutaneously) twice weekly in addition to the docetaxel dosing schedule observed in Cohort A.
• Cohort C: Six patients received docetaxel at a higher dose (52 mg/m²) weekly combined with etanercept (25 mg subcutaneously) twice a week for six weeks.
• Cohort D: Eight patients received docetaxel (52 mg/m²) weekly combined with etanercept (25 mg subcutaneously) twice a week and G-CSF (5 ug/kg per day for four consecutive days starting the day after each docetaxel administration).
• Outcomes were assessed at baseline and each week.

N = 28

MEDIAN AGE = 56 years

AGE RANGE = 25–83 years

MALES = 17

KEY DISEASE CHARACTERISTICS: Most had received previous chemotherapy and/or radiotherapy and had multiple disease sites. The most common disease site was non-small-cell lung.

EXCLUSION CRITERIA: Patients were excluded if they were scheduled for major surgery, radiotherapy, or chemotherapy within 28 days of study entry or had brain metastases, serious infections, or psychiatric disorders that would interfere with consent or follow-up; pre-existing moderate-to-severe peripheral neuropathy; or cardiac disease. Pregnant or lactating women also were excluded.

• PHASE OF CARE: Active treatment

• Pilot feasibility study

• National Cancer Institute (NCI) fatigue grade assessment
• Fatigue Symptom Inventory (FSI)

Patients randomly were selected to receive etanercept/docetaxel. Less fatigue was self-reported in comparison to patients who received docetaxel only (p < 0.001). The FSI Interference score of Cohort A was significantly greater than the score of Cohort B (p < 0.001). Patients receiving additional cycles for treatment (Cohorts B,C, and D) did not experience worsening fatigue.

• Pilot study and therefore lacking a neutral comparison group
• Small sample size
• Fatigue assessment endpoints were not predetermined

To investigate whether moist skin care with 3% urea lotion will reduce acute radiation (RT) skin toxicity.

Irradiated skin of inpatients was treated with 3% urea lotion (Eucerin^® 3%, Beiersdorf).

Outpatients were treated with either urea lotion or powder, depending randomly on the date when they started RT (Azulon^®, Baxter Oncology GmbH, formerly ASTA Medical AWD).

They were instructed to avoid mechanical, chemical, or thermal irritations of the skin, to wear light clothes, and to omit jewelry. Men were told to use an electric shaver.

Starting with the first day of irradiation, irradiated skin was treated with lotion or powder twice daily. At the occurrence of a skin reaction grade I or II, the lotion or powder was given at least five times per day. If skin lesions grade III or IV occurred, treatment with lotion or powder was stopped and the patient received appropriate wound care programs (povidone-iodine and zinc ointments). Findings were compared to those of historical controls.

• The sample was comprised of 88 patients (63 urea lotion, 25 historical controls).
• Age was not reported.
• Of the patients, 85% were male and 15% were female.
• Patients had carcinomas of the head and neck and were undergoing RT with curative intent.
• Mean total dose was 60 Gy (range 50–74 Gy).

Multiple sites in Germany

The study was a single-arm clinical trial with a historical control comparison.

Patients were evaluated weekly for acute skin reactions according to the Radiation Therapy Oncology Group (RTOG) score.

To exclude sampling errors and scoring differences between different observers, all skin evaluations were performed by the same physician.

Results showed that controls had a higher prevalence of skin toxicities at all grades, at lower radiation doses (p < 0.05).

Moist skin care with 3% urea lotion may delay the occurrence of acute RT-induced skin reactions.

• The sample of patients with head and neck cancers was very diverse, and treatment plans varied substantially. A 6-mev machine tends to have more skin toxicity than an accelerator with the ability to perform multienergy.
• A larger proportion of controls were also receiving chemotherapy, which may have skewed the results.
• The study had a relatively small sample and was not randomized.

To evaluate the effectiveness of regional cooling on palmar-plantar erythrodysesthesia (PPE).

Patients received pegylated liposomal doxorubicin (PLD) every 28 days, with dosages ranging from 30 mg/m² to 50 mg/m².

Group 1 (n = 17) used regional cooling. The regional cooling protocol (RCP) included administration of ice packs to the wrists and ankles, and iced liquids were available for consumption during PLD infusion. In addition, patients were encouraged to use the ice packs for up to 24 hours after completion of the PLD infusion.

Group 2 (n = 3) did not use RCP. Patients were instructed to avoid ingestion of hot foods or liquids, avoid contact with hot water and direct sunlight, and minimize friction to the hands and feet for 72 hours post-PLD treatment.

• The study reported on a sample of 20 female patients with recurrent epithelial ovarian cancer who received PLD.
• The median number of PLD cycles was five.

University of Nebraska Medical Center in Omaha

This was a retrospective analysis of 20 patients’ records.

PPE was graded from 1 to 4; however, the authors did not specify what grading system was used.

The frequency and severity of PPE was reduced in 17 women who used the RCP, compared to three women who did not use those measures (p = 0.047).

Regional cooling around the wrists and ankles was well tolerated and had a high degree of compliance during chemotherapy administration.

• This was a retrospective review of records.
• The sample size was small.
• The description of the measurement method used to grade PPE symptoms was insufficient; reliability and validity were unclear.

To evaluate the feasibility and effectiveness of a patient-performed daily spirometry as an early warning tool and the use of a positive expiratory pressure (PEP) flute device to prevent pneumonia among outpatients undergoing treatment for acute myeloid leukemia (AML)

All patients received a 45-minute face-to-face educational session about pneumonia prevention and assessing for early signs, plus instructions on how to use a spirometer and record findings daily. The intervention group received PEP flutes and instructions for use. All patients received instructions for contacting a healthcare provider if symptoms occurred. The primary outcome was occurrences of pneumonia.

• N = 80 (40 per group)   
• MEAN AGE = 56 years (both groups)
• MALES: 63.75%, FEMALES: 36.25%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: AML

• SITE: Multi-site   
• SETTING TYPE: Multiple settings    
• LOCATION: Copenhagen, Denmark

• PHASE OF CARE: Active antitumor treatment

• Randomized, controlled trial

• Adherence to the PEP flute was measured by patient feedback at weekly meetings (unclear if verbal or written).
• Pneumonia was measured by x-ray verification of infiltrates, bronchoalveolar lavage or sputum cultures, and electronic transfer of data from the spirometer to show adherence.

The use of FEV1 to monitor for early onset pneumonia can be effective. The use of the PEP flute significantly decreases the occurrence of pneumonia.

• Small sample (< 100)
• The findings were reported on a total of 80 patients, although three dropped out in the beginning of the study, seven during induction chemotherapy, and another eight because of distress.
• Table II reported on pneumonia findings in all 80 patients.
• Statistical considerations for missing data were unclear.
• An adjustment was made for the FEV1 analysis (10 patients removed because of comorbidities and/or very poor lung capacity, 4 of whom had cases of pneumonia).

Direct patient education on the use of spirometry to evaluate FEV1 and PEP flutes is effective. FEV1 findings can potentially aid with early pneumonia diagnosis, and the use of the PEP flutes can help prevent pneumonia.

To evaluate the effectiveness of systemic antibiotic treatments (oral doxycycline) and local treatment for skin rash in patients receiving cetuximab.

Patients were prospectively evaluated by dermatologists from two phase 2 trials between October 2003 and May 2004. Dermatologists determined they would treat four patients with oral doxycycline; in three of those patients, a topical treatment (retinoid) was given as well. Other patients were treated with benzoyl peroxide (n = 1) or fusidic acid (n = 1).

• The study reported on a sample of 13 patients with metastatic colorectal cancer who were receiving cetuximab once per week (400 mg/m² on week 1 and 250 mg/m² thereafter).
• The cetuximab treatment was associated with oxaliplatin, 5-fluorouracil, and fusidic acid, or irinotecan.

Service de Dermatologie et Service d’Oncologie, Hôpital Tenon, in Paris, France

This was a prospective trial.

Rash intensity was graded as mild, moderate, or severe.

• Eleven patients treated with cetuximab (85%) developed skin lesions.
• The six treated patients responded to classical modalities of doxycycline (n = 4), benzoyl peroxide (n = 1), and fusidic acid (n = 1). Skin lesions resolved in four weeks.
• Five patients were not treated because the acneform rash was mild. In those patients, the rash resolved spontaneously, although cetuximab was continued at the same dose.

Antibiotic treatments (oral doxycycline) and local treatments given to six patients receiving cetuximab were effective in resolving skin lesions.

• This was a very small, nonrandomized trial.
• The description of the measurement tool or method used to grade rash symptoms was inadequate, with no reliability and validity.
• Treatment was determined by the dermatologist.
• A combination of interventions was used; therefore, determining the effectiveness of the individual interventions is difficult.

To evaluate the effectiveness of systemic antibiotic treatments (oral doxycycline) and local treatment for skin rash in patients receiving cetuximab.

Patients were prospectively evaluated by dermatologists from two phase 2 trials between October 2003 and May 2004. Dermatologists determined they would treat four patients with oral doxycycline; in three of those patients, a topical treatment (retinoid) was given as well. Other patients were treated with benzoyl peroxide (n = 1) or fusidic acid (n = 1).

• The study reported on a sample of 13 patients with metastatic colorectal cancer who were receiving cetuximab once per week (400 mg/m² on week 1 and 250 mg/m² thereafter).
• The cetuximab treatment was associated with oxaliplatin, 5-fluorouracil, and fusidic acid, or irinotecan.

Service de Dermatologie et Service d’Oncologie, Hôpital Tenon, in Paris, France

This was a prospective trial.

Rash intensity was graded as mild, moderate, or severe.

• Eleven patients treated with cetuximab (85%) developed skin lesions.
• The six treated patients responded to classical modalities of doxycycline (n = 4), benzoyl peroxide (n = 1), and fusidic acid (n = 1). Skin lesions resolved in four weeks.
• Five patients were not treated because the acneform rash was mild. In those patients, the rash resolved spontaneously, although cetuximab was continued at the same dose.

Antibiotic treatments (oral doxycycline) and local treatments given to six patients receiving cetuximab were effective in resolving skin lesions.

• This was a very small, nonrandomized trial.
• The description of the measurement tool or method used to grade rash symptoms was inadequate, with no reliability and validity.
• Treatment was determined by the dermatologist.
• A combination of interventions was used; therefore, determining the effectiveness of the individual interventions is difficult.

To assess the feasibility of inspiratory muscle training (IMT) in the lung cancer population and to explore changes in outcomes

Patients were randomized to either the standard care group or the intervention group, which received standard care and intervention of IMT, consisting of two supervised sessions, then home self-delivery of IMT with provided device (pressure threshold device) in five sessions weekly for 12 weeks of 30 minutes per day divided over two sessions. Assessments were completed at 4, 8, and 12 weeks.

• N = 46  
• MEAN AGE = 69.5 years 
• AGE RANGE = 51–85 years
• MALES: 80.4%, FEMALES: 19.6%
• KEY DISEASE CHARACTERISTICS: The study included patients with primary lung cancer or mesothelioma, refractory dyspnea, prognosis of less than three months as judged by a clinician, and an O₂ saturation less than 85% at rest.
• OTHER KEY SAMPLE CHARACTERISTICS: The study excluded patients who had received radiation to the chest within four weeks or chemotherapy within two weeks. It generally included patients with stable disease who were off treatment.

• SITE: Multi-site   
• SETTING TYPE: Multiple settings—large cancer centers, but participants completed intervention in their homes
• LOCATION: Two sites in the UK and one in Cyprus

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Palliative care 

• Randomized, controlled trial

• Spirometry assessment (physiologic data)—forced vital capactiy (FVC), forced expiratory volume (FEV1), FEV1%, and peak expiratory flow (PEF)
• Severity of breathlessness, distress caused by breathlessness, ability to cope with breathlessness, and satisfaction with management of breathlessness all assessed by patient self-report on a 0–10 numeric rating scale
• Modified Borg Breathlessness Scale (MBBS) 
• Short Form Chronic Respiratory Disease Questionnaire (SF-CRDQ)
• Hospital Anxiety and Depression Scale (HADS)
• Clinician assessement and patient self-report or hypercapnia (safety) 
• Compliance measured with patient-maintained training diary
• Chronic Respiratory Disease Questionnaire (CRDQ)

This trial showed that IMT is feasible and acceptable for patients with lung cancer. In comparison of IMT group and control group, several outcomes, including worst breathlessness, average breathlessness, distress from breathlessness, ability to cope with breathlessness, satisfaction with management of breathlessness, fatigue, and depression and anxiety had improved for the IMT group over the control group. No differences were seen in spirometry and breathlessness between groups.

IMT is feasible and acceptable for patients with lung cancer and improved outcomes were seen for patients receiving IMT. However, this trial had a small sample size, so it cannot adequately draw solid conclusions regarding outcomes for patients with lung cancer undergoing IMT for breathlessness. Larger trials should be conducted to evaluate this.

• Small sample (< 100)
• Findings not generalizable
• This study included only patients with lung cancer.
• Does not include those with breathlessness from metastasis
• Does not quantify number of patients with other underlying lung disorders that may contribute to breathlessness
• Excludes only those with unstable COPD

IMT may be of benefit for the treatment of breathlessness, but data are too weak due to the small sample size to strongly recommend IMT. In addition, the study included only patients with lung cancer. This study is inadequately powered to draw conclusions about outcomes and does not address any patients experiencing breathlessness from nonthoracic malignancies.

To determine if maintenance acupuncture is beneficial in sustaining improvements in fatigue after a course of acupuncture.

Patients in a previous six-week acupuncture trial were rerandomized to three groups:  maintenance self-acupuncture, therapist-delivered maintenance acupuncture, or a control group receiving usual care. Maintenance therapy lasted for four weeks. Standard acupuncture points were used, and sessions were weekly. Data were collected at the end of four weeks and at 12 weeks after rerandomization.

• The study reported a sample of 151 women with breast cancer.
• Mean age was 53 years.
• Patients had undergone surgery, and the majority had received prior chemotherapy and radiotherapy.
• Mean time since completion of treatment was 20 months.
• The majority of patients were married and employed full- or part-time.

• Single site
• Multiple settings
• United Kingdom

Patients were undergoing the transition phase of care after active treatment.

The study was a randomized, controlled trial.

• Multidimensional Fatigue Inventory (MFI)
• Hospital Anxiety and Depression Scale (HADS)
• Functional Assessment of Cancer Therapy-Breast (FACT-B)
• Patients' logs of self-needling

Results showed a trend of fatigue improvement in the combined acupuncture groups compared to the control; the trend was not significant. In regard to results reflecting anxiety or depression, the study showed no differences between groups. Patients' logs indicated that patients performed self-needling as planned.

Findings suggested that it is feasible for patients to maintain acupuncture treatment through self-needling. Compared to symptom improvement in patients in the control group, symptom improvement in patients undergoing maintenance acupuncture through self-needling or through delivery by a therapist was not significant.

• The study had risks of bias due to no blinding and no appropriate attentional control condition.
• The authors did not discuss other treatments or interventions aimed at fatigue. If the authors used additional management approaches, the approaches are unknown.

The study showed that patients can be taught to deliver their own acupuncture treatments effectively by self-needling. The study did not demonstrate that ongoing acupuncture, or maintenance acupuncture, had any effect on fatigue, anxiety, or depression.

To assess the effectiveness of acupuncture for cancer-related fatigue (CRF) in women with breast cancer.

Women were randomly assigned to acupuncture or enhanced usual care groups. Usual care enhancement consisted of providing a booklet about CRF, diet, exercise, and sleep. The intervention group was offered six acupuncture treatments over six weeks. Sessions lasted 20 minutes each and involved unilateral or bilateral needles at three points. No rotation or flicking of needles was performed. Patients were followed for 18 weeks. Outcome measures were recorded at six weeks.

• The sample was comprised of 246 participants.
• Mean age was 52.5 years (range 25–80).
• All participants were female.
• All participants had breast cancer with no distant metastases. 
• All participants had completed antitumor treatment within one month to five years prior to enrollment. 
• All participants had a baseline fatigue of at least 5 on an 11-point screening scale. 
• Average time since diagnosis was 20.5 months.
• Mean duration of fatigue was 16.5 months.
• Participants were predominantly white, married, and had at least a college education.

• Multisite
• Outpatient
• United Kingdom

The study has clinical applicability for late effects and survivorship.

The study was a randomized, controlled trial.

• Multidimensional Fatigue Inventory (MFI)
• Hospital Anxiety and Depression Scale (HADS)
• Functional Assessment of Cancer Therapy-Breast (FACT-B)
   

The difference score between the control and acupuncture groups for fatigue was –3.11 (95% confidence interval [CI] [–3.97, –2.25]; p < 0.001). Intention-to-treat (ITT) analysis, using an assumption of no improvement for patients whose week six outcome data were missing, continued to show a significant difference (–2.49; p < 0.001). Week six outcomes, as reflected in HADS and FACT-B scores, were significantly improved from baseline in patients who received acupuncture (p < 0.001).

Findings showed that acupuncture as provided was effective in reducing fatigue over a six-week period among survivors of breast cancer.

• The study had a risk of bias due to no blinding.
• Data were missing for 20.3% of the acupuncture group and 13.3% of the control group. The authors performed conservative ITT analysis to account for the missing data. For the intervention group, the authors reported complete data only.
• The authors did not discuss data relative to anxiety or depression.

Findings showed that acupuncture was helpful in reducing fatigue in patients with breast cancer who had completed antitumor treatment. The study supports the effectiveness of acupuncture for the treatment of fatigue.

The study was a randomized, controlled trial of acupuncture (n = 15); acupressure (n = 16); and sham acupressure (n = 16). Acupuncture included six 20-minute sessions over two weeks. Acupressure involved self-applying pressure to the same points daily. Sham acupressure involved self-applying pressure to nonenergy points. The selected acupuncture points were energy points that have been used for more than 2,000 years.

• The study included 47 patients with cancer who experienced moderate to severe fatigue (greater than 5 on a 1–10 scale) who were at least one month postchemotherapy.
• Of the participants, 32 of 47 were female and all but one were Caucasian.
• Mean age was 53.4 years (range 20–76).
• Patients were excluded if they had needle phobia, platelets less than 50,000, hematocrit (HCT) less than 30, Karnofsky Performance Status (KPS) less than 70, or were on steroids.

Patients were recruited from an outpatient clinic, an acupuncture treatment setting in a hospital in the United Kingdom, or in their own homes.

The study was a small randomized, controlled trial with blinding between two acupressure conditions.

• Multidimensional Fatigue Inventory (MFI) pretreatment and at two and four weeks
• Daily log for acupressure groups

The study included an intention-to-treat (ITT) analysis. Significant improvements existed in general fatigue (p < 0.001), physical fatigue (p = 0.016), activity (p = 0.004), and motivation (p = 0.024). Patients showed 36% improvement in acupuncture, 19% in acupressure, and 0.6% in sham acupressure. The effect was not sustained at the same level after two weeks.

• The drop-out rate was 15%.
• It was not possible to blind the acupuncture group.
• Travel to the clinical site to receive acupuncture or acupressure treatment was a barrier.

Spot bleeding was observed in two cases. Trained acupuncturists are necessary. A detailed description of acupuncture was given using Standards of Reporting Interventons of Controlled Trials of Acupuncture (STRICTA) guidelines.