To examine the feasibility and efficacy of a Qigong intervention for improving older prostate cancer survivors’ levels of fatigue and distress

Qigong intervention twice weekly sessions for 12 weeks led by Qigong master for one hour with DVD provided for home practice. Qigong incorporated standing and sitting exercise, with increased standing exercise with each session. Exercises included five minutes of meditative breath at the beginning and end of each session, opening of the nine gates, muscle change, cavity presses, collecting energy of heaven and earth, rocking chair, Tai Chi ruler, hands skimming the water, pushing and pulling space, cloud hands, body weight resistance

Stretching intervention led by instructors from the exercise and sport science department twice weekly for one hour for 12 weeks. Avoided movement similar to meditation; used sitting and standing that increased intensity with each session. A DVD also was provided for home practice.

• N = 29    
• MEAN AGE = 72 years
• MALES: 100
• KEY DISEASE CHARACTERISTICS: Prostate cancer, five-year median diagnosis, 48% on ADT
• OTHER KEY SAMPLE CHARACTERISTICS: No significant difference was noted between those who completed and those who withdrew from intervention.

• SITE: Single site  
• SETTING TYPE: Multiple settings  
• LOCATION: Survivorship and wellness center as well as and home practice

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

• Non-blinded RCT, active control

• FACIT–Fatigue
• Brief Symptom Inventory
• Borg scale
• Self-report
• Class attendance and retention

Baseline fatigue between groups was not statistically different. Change in fatigue from baseline was statistically improved in the Qigong group compared to the stretch group (p = .02). Home practice reports were not significantly different. Sixty-nine percent in the Qigong arm had a minimally important difference of 3 or more points compared to 38% in stretching. BSI score between groups was significantly different for somatization (p = .048), anxiety (p = .003), and global severity index (p = .002).

Fatigue and distress were improved in the Qigong group compared to stretching. High attrition was noted in both groups.

• Small sample (< 30)
• Risk of bias (no blinding)
• Findings not generalizable
• Subject withdrawals ≥ 10%

Qigong as an intervention is a low-risk option for treating fatigue in patients with prostate cancer. Larger RCTs are needed.

To assess the impact of massage therapy on intermediate-term anxiety in patients undergoing radiation therapy

Patients were randomized to massage therapy and control groups. Patients in the massage therapy group rated anxiety before and after massage sessions, and control patients rated their anxiety 15 minutes before radiation treatment. All massage sessions took place before the radiation treatment over 10 consecutive days. Massage consisted of a 15-minute chair massage with a combination of effleurage and petrissage. Patients did not disrobe for the therapy, and no lotion was used. Massage therapists participated in a training course specifically targeting the care of patients with cancer. All therapy was standardized, but was adapted as necessary to avoid any massage to the treatment field. The massage therapist assessed anxiety in all patients using a visual analog scale (VAS) every day during the study.

• The sample included 100 participants.
• Mean age in the control group was 58 years; mean age in the massage group was 60 years (range = 35–85 years).
• The sample was 68% females and 32% male.
• Most participants had breast or head and neck cancers.

• Single site
• Outpatient setting
• Montreal, Quebec, Canada

Active treatment phase

A randomized controlled trial design was used.

• Visual Analog Scale (VAS): Ranges from 0 (not anxious at all) to 10 (the most anxious I have ever been), using a 10 cm ruler with a slide bar
• Spielberger State-Trait Anxiety Inventory (STAI)

The mean VAS score before massage was 4.0 and after massage was 2.2, which was a 45% decrease in anxiety (p < 0.001). Patients in the massage group showed a 15% decrease in anxiety scores from the first to the last session, and patients in the control group experienced a 19% decrease over the same time interval. Both groups had similar scores for state and trait anxiety at baseline. There were no differences in state anxiety between groups at the last session, indicating no intermediate effects on anxiety. VAS scores declined over time for both groups.

Massage therapy as used in this study was associated with a significant immediate reduction in anxiety, but appears to have little or no effect on intermediate-term anxiety. Anxiety over the course of radiation treatment declined for both groups.

• The study had no appropriate control group.
• The type of massage given was limited (only 15-minute chair massage), which could have influenced results.
• The control group met with the massage therapist for anxiety assessment, but it is not clear whether this provided an adequate attentional control.
• Bias may have been present since the massage therapist was the person who administered the VAS assessment to all patients.
• The study concluded after a 10-day period.
• The duration of therapy for participants was not described, so it is not clear how this reflected an intermediate point in therapy.
• The sample size was not sufficient to allow for subgroup analysis to determine potential differences in effect by diagnosis or other subject groups.
• Baseline VAS scores were relatively low on average in both study groups and was lower in the control group (3.2), which likely influenced effect sizes that could be seen.

Findings suggest that a brief chair massage can be effective for immediate reduction in anxiety, and this may be helpful for certain patients who are very anxious in beginning treatments. Because anxiety in all patients declined over time, and all subjects were seen by a massage therapist prior to each treatment, it may suggest that regular attention to anxiety in interaction with patients may be helpful for anxiety reduction over the course of treatment. This is an area that could be studied. The length and type of massage could influence findings, suggesting that further research in this area should incorporate evaluation of various types and duration of massage.

To examine the feasibility and effect of a telephonic cognitive behavioral intervention to facilitate research participation and enhance quality of life among African American prostate cancer survivors and their partners

Consenting patients and their partners provided pretreatment measures and then were randomly assigned to either partner-assisted coping skills training (CST) or usual care (control condition). In the control group, individuals received routine care provided through their medical outpatient program. The CST intervention was designed to train survivors and partners in skills for managing symptoms, including provision of information about prostate cancer and possible long-term side effects, teaching problem solving skills and training in cognitive and behavioral coping skills such as communication, relaxation, and activity pacing. CST was provided in six one-hour telephone calls approximately once a week. Sessions were audiotaped and reviewed for protocol adherence. All subjects completed post-treatment study measures at the end of the six-week period.

• The sample included 30 patient participants and 30 spouse participants.
• The mean age was 62.1 ± 8.9 for patients and 58.7 ± 9.8 for partners.
• Females: Partner gender was not stated, so it is assumed that all partners were female (n = 30).
• Males: All patients were male (n = 30).
• All patients had prostate cancer.
• Time since treatment ranged from 1 week to 4 years, with an average of 18 months.
• 86% of patients and 93% of partners had completed at least a high school education, 53% of survivors were working full-time, and 37% were retired.
• Among partners, 46% were working full-time, and 46% were retired.
• Annual income was $30,000 or greater in 67% of the sample.

• Multi-site
• Outpatient setting
• Multiple practices and clinics in North Carolina

A randomized controlled trial design was used.

• Self-Efficacy for Symptom Control Efficacy (SESCI) patient and partner versions
• Expanded Prostate Cancer Index Composite (EPIC)
• Short Form 36 (SF-36) physical function and mental health scales
• Profile of Mood States Short Form (POMS - SF)
• Caregiver Strain Index (CSI)

Seven couples initially randomized to the treatment group withdrew (approximately 30%) primarily because of difficulties in scheduling treatment sessions.

Men who participated in the CST reported significantly higher quality of life related to bowel symptoms (p = 0.042). There were no significant differences between groups in general health, negative mood among partners, caregiver strain, or caregiver self-efficacy. Within the CST group, pre-post treatment measurement demonstrated significant improvement in reported bowel symptoms (p < 0.05), hormonal symptoms (p < 0.05) and self-efficacy (p < 0.05). There were no significant differences between pre and post-treatment measures among the partners (no effect on caregivers).

The telephone intervention was able to be delivered to the majority of participants, suggesting that this approach may be feasible for the delivery of coping skills training. Significant effects to improve caregiver self-efficacy and experience were not seen. This type of intervention appears to be helpful to patients in the area of managing side effects of prostate cancer.

• The sample had less than 30 participants.
• Eligible patients had good performance scores for inclusion, and the majority were working full-time. This suggests that the sample was relatively healthy and caregiving needs may have been low. This may have influenced the lack of significant findings among intimate partners related to the intervention.
• There is no information about what was included in the usual care group in terms of any education, frequency of follow-up, etc.
• There was no attentional control provided in this study. Although the study demonstrated that the telephonic intervention was feasible for the majority of subjects, there was a 30% attrition rate. This points to practical difficulties in provision of such interventions and suggests that those who completed the study may have been those who were biased in terms of their expectations of effect or were most highly motivated to participate.
• This is not generalizable to all patients with prostate cancer because the majority of survivors in this study underwent surgical treatment, and the population included only African Americans.

Telephonic approaches to provide education, counseling, and CST is a promising approach for the provision of patient care, but scheduling sessions, particularly when patients and caregivers are working full-time, is a challenge. This type of intervention appears to be effective in terms of symptom and side-effect management among patients who are receptive to this type of approach, but the impact on caregiver strain and burden is unclear.

To examine the controversy regarding washing the skin during or after a course of radiation therapy (RT)

Participants were randomized to one of three washing policies: (a) not washing, (b) washing with water alone, or (c) washing with soap and water. Assessment of skin reactions was weekly during treatment and at two and four weeks after treatment was completed.

• The study sample (N = 95) was comprised of female patients.
• Age ranged from 33–75 years.
• All patients were receiving postoperative RT following breast local excision or mastectomy.
• Prescribed doses were 4,500 cGy or 4,700 cGy in 20 fractions in 28 days.

The study took place at Mercy Clatterbridge Hospital in Bebington, Mercyside, United Kingdom.

The study used a randomized controlled trial design.

• Patients graded their symptoms or itching and pain in the treated skin as none (0) to severe (3).
• Skin was graded according to the European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group (EORTC/RTOG) Scale from 0 (none) to 3 (severe).
• Desquamation was scored as none (0), dryness of the skin (1), moderate flaking (2), severe flaking (3) or patchy moist desquamation (4).

Itching was the main local symptom experienced; it was present at some point in 77% of the patients. In all groups the average itching score rose progressively during treatment, with a maximum at four weeks after starting treatment. Participants randomized to washing had itching scores either similar to or less than those not washing. Several of the comparisons showed a statistically significant reduction in itching at p < 0.05 with washing. Pain in the treated skin was reported by 31% of participants during the observation period. No clear trends were observed in the different washing policy groups. The average scores for erythema rose progressively during observation with a maximum at four to six weeks. There was little difference between washing groups, and a small trend for the non-washing groups to have the highest reactions. Several comparisons showed a statistically significant reduction in erythema associated with washing (p < 0.05). Average scores for desquamation showed maximum reactions at six to eight weeks after starting treatment. Patients who were washing had markedly lower scores than patients who were not washing, with some comparisons reaching statistical significance (p < 0.05 washing compared with p < 0.01 not washing).

Findings support allowing patients to wash during RT with either soap and water or water alone.

• Generalization of findings is not completely clear.
• Approximately half of the participants were prescribed a topical cream for their skin reaction (n = 45), and whether the cream had any effect on study findings is not clear.
• No restriction was placed on the frequency of washing in any of the groups.

The objective of the study is to determine if routine application of oxygen in patients who were near death would be beneficial as measured by relief of distress.

At baseline, a trained observer who was blinded to the current type of NC flow (oxygen or medical air) of the patient collected data about the respiratory status of each patient. Patients not in respiratory distress were then randomly alternated through low-flow oxygen, medical air, or room air on an NC on a 10-minute washout rotation. Each patient received each type of air twice for a total of six rotations per patient.

• The study reported on a sample of 32 patients who ranged in age from 56-97 years.
• The sample was 34% males and 66% females.
• Included in the study were patients who were referred for palliative care consultation, enrolled in hospice, near death, at risk for respiratory distress, and institutionalized.
• The study reported on a limited number of patients with cancer (9% lung cancer, N = 3).

The multi-site study was conducted in a university hospital or free-standing hospice facility in the Midwestern United States.

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

The double-blind study repeated measures with patient as own control.

• Respiratory distress observation scale (RDOS) - observation of respiratory distress symptoms
• Palliative performance scale (PPS) - nearness to death
• Reaction Level Scale (RLS85) to assess consciousness
• Oxygen saturation and end tidal carbon dioxide via Nellcor N-85 capnograph/oximeter (Covidien, Mansfield, MA)

Most patients (84%) had oxygen flowing at baseline. Three patients did not tolerate switching from oxygen to no flow and were restored to baseline with no further rotations. One patient died during the fourth gas/flow encounter without increased distress. No oxygen adverse effects (e.g., nosebleeds) occurred during the study. Average baseline respiratory distress was 1.47 (scale 0-4), with no difference over the study period. Baseline oxygen saturation and RDOS were inversely related. Neither consciousness nor nearness to death correlated to baseline RDOS, but consciousness was significantly correlated to nearness of death.

Routine application of oxygen does not reduce dyspnea at the end of life and should be used as an n of one trial in patients near death with observed dyspnea.

• The study had a small sample size of less than 100.
• The study had a risk of bias due to sample characteristics and no blinding.
• Key sample group differences could influence results.
• This small sample size with different medical diagnoses may not account for different types of airway/respiratory compromise and the potential variance in benefit from oxygen (e.g., heart failure, secretions, airway obstruction).

Oxygen administration near the end of life for management of observed dyspnea is scientifically logical, but this study suggests no proven clinical benefit. Costs to bring oxygen into the home and train caregivers in its administration may not be necessary based upon this study’s findings. In addition, the addition of the oxygen delivery device may be uncomfortable or produce unwanted adverse effects. The limited number of patients with cancer in this study limits generalizability to this population.

To evaluate an intervention that was designed to improve the problem-solving abilities of family caregivers* of patients with advanced cancer**. Authors tested whether the intervention (a) enhanced positive problem-solving skills and decreased negative problem solving, (b) enhanced confidence in caregivers’ ability to perform caregiving activities, and (c) decreased caregivers’ emotional distress.

* Caregivers were defined as those unpaid family members assuming responsibility for homecare needs of an individual with advanced cancer.
** Advanced cancer was defined as patients with estimated survival prognosis of three to six months.

A one-hour intervention used explanations and a slide presentation or flip charts of problem solving. The intervention was given to caregivers only once, at the time of recruitment. The intervention involved:

1. Introducing examples of problem-solving techniques from a Home Care Guide  for Advanced Cancer, which was developed by the American College of Physicians to help caregivers COPE (be Creative, Optimistic, Plan, and obtain Expert information).
2. Encouraging the caregivers to use a five-step approach to address problems. These steps were to (a) define the problem, (b) identify when to seek professional help with the problem, (c) identify what they (caregivers) could do to help, (d) consider possible obstacles to their caregiving plan, and (e) carry out and adjust the plan.

• The sample included 34 family caregiver participants.
• Mean age of caregivers was 53.6 years. No SD or range was mentioned.
• Caregivers were 67.6% (n = 23) female and 32.4% (n = 11) male.
• Caregivers had to be those giving care to patients diagnosed with advanced cancer, defined as having an estimated survival prognosis of three to six months.
• To be included in the study, participants had to be 18 years or older, be able to speak and read English, be able to give written consent, and be clear of severe visual, hearing, or cognitive impairments that would interfere with their ability to participate.

• Single site
• Inpatient setting
• Teaching hospital (University Health Network in Toronto, Ontario, Canada): While the patient attended a clinical visit, the research assistant met separately with the caregiver.

• End-of-life care phase
• Elder care; palliative care

A one-sample pretest/post-test design was used. There was no control group. Survey data were collected at baseline (recruitment) and then by phone four weeks after the intervention was done.

• Social Problem-Solving Inventory–short form (SPSI-SF): Used to assess caregivers’ ability to problem-solve. The scale has five subscales representing: (a) positive problem-solving orientation, (b) negative problem-solving orientation, (c) rational problem-solving orientation, (d) impulsivity/carelessness scale, and (e) avoidance style scale.
• Profile of Mood States–short form: Used to assess emotional well-being. This was an established and reliable tool. The scale includes six subscales: (a) tension-anxiety, (b) depression-dejection, (c) anger-hostility, (d) fatigue-inertia, (e) vigor-activity, and (f) confusion-bewilderment.
• Caregiver Assistance Scale (CAS): Used to assess the level of assistance provided by caregivers to patients in activities of daily living, instrumental activities of daily living, and treatment-related activities. This was an established and reliable scale.
• Caregiver Self-Efficacy Scale: Developed by the authors to assess caregivers’ confidence in their ability to perform each of the caregiving activities. The seven-point scale has ratings ranging from one (not very confident) to seven (very confident). The authors averaged the scores, yielding an overall confidence score ranging between one and seven, with higher scores indicating greater confidence. They calculated an excellent internal consistency of this developed scale in the sample (α = 0.90).

The authors provided a good description of how the original sample went from 112 to 34 caregivers, and the basis for attrition or exclusion were reviewed clearly, giving good insight into factors to consider when researching this group of caregivers of patients with advanced cancer. Reasons that led to shrinking of the sample included (a) some patients who were identified with advanced cancer did not need assistance at home, thus they did not have caregivers (n = 7), (b) some caregivers declined participation (n = 34), (c) some participating caregivers did not complete baseline survey because they changed their mind, their patient died, they were not coming back to the hospital in time to complete the intervention, or they had English language difficulty (n = 13), (d) some caregivers who completed the baseline data did not come back later to receive the intervention (n = 11), (e) some caregivers completing the baseline data and the intervention did not complete the follow-up survey (n = 6), and (f) some caregivers were wrongly identified (patients had advanced cancer but responded to curative treatments, or patients were outliers in terms of the length of time they had been diagnosed with advanced cancer) (n = 7).

Other significant findings include the following.

• One significant difference was identified between participant and nonparticipant characteristics: Participants gave care to patients who had cancer for a shorter period of time.
• The mean time between baseline assessment and follow-up assessment was 4.8 weeks (1.28).
• Caregivers showed significant improvement in their positive problem-solving (mean score at baseline [pretest] was 12.3 [3.56] and at follow-up was 13.7 [3.80], p = 0.054); the authors used a p level of 0.06 to judge significance for this finding.
• Caregivers showed significant improvement in their confidence in caregiving activities (mean at baseline [pretest] was 6.1 [0.65] and at follow-up was 6.3 [0.60], p = 0.059); the authors used a p level of 0.06 to judge significance for this finding.
• Caregivers showed significant improvement in emotional tension (mean at baseline was 1.5 [0.97] and at follow-up was 1.2 (0.85), p = 0.024).
• There was a significant positive correlation between caregivers’ reported levels of fatigue at baseline and their level of impulsivity/carelessness problem-solving subscale score (SPSI-SF) at follow-up (r = 0.40, p < 0.02).

Overall, the findings clearly show potential evidence that the intervention affected caregivers positively. Given that improvements were noted even though participants already showed that they have good levels of confidence in their abilities and problem-solving skills at baseline, the findings strongly suggest that the intervention might have even greater potential among those with lower levels of confidence in their caregiving and problem-solving abilities. The intervention influenced one aspect of emotional well-being (tension subscale) and one aspect of problem-solving (positive problem-solving subscale), suggesting that a modified or more comprehensive or frequent intervention may improve other aspects of emotional well-being or problem-solving. Researchers of caregivers of patients with advanced cancer should consider and address the serious challenges that they may encounter in recruiting this group of caregivers.

• The sample was small, with less than 100 participants.      
• Baseline sample and group differences existed.  
• Risk of bias existed due to no control group, no blinding, and no random assignment.
• Key sample group differences existed that could influence results.*
• Subject withdrawals were 10% or greater.
• No information was provided about whether the research assistant who conducted the intervention with participating caregivers had received or had training or expertise in training others in problem-solving. This is an important piece of information because the value or influence of the intervention would be as good as the training that the caregivers received. 
• The study sample was reduced by 50% of caregivers consented to the study.
• * The findings regarding significant improvements in caregivers' confidence and positive problem-solving are borderline, and one can argue that p levels of 0.059 and 0.054 are bordering significance but not significant as the authors interpreted them. The customary p level is < 0.05; with no correlations shown, it is hard to accept the interpretation as significant as the authors relaxed the p level to 0.06.

Nursing care of patients with advanced cancer should be extended to include care of their caregivers, as they are key in providing care at home. This brief problem-solving intervention significantly improved the emotional tension in caregiver participants, suggesting the value of its use in palliative care settings. The fact that a significant difference existed between participants and nonparticipants in relation to the length of time their patients were diagnosed with cancer suggests that the longer caregivers provide care, the less likely they would be to participate in interventions. This suggests that they (a) may have figured out on their own how to manage the caregiving burden, or that they are too exhausted to participate, or (b) need different types of interventions that meet them where they are, either at home or in their locale, rather than require them to drive to where interventions would be conducted. This findings suggest that researchers may need to focus on caregivers of patients with new onset of disease or those who have had the disease for a short period. Any interventions with these caregivers should be set up in a way that decreases the demand on their time and meet them where they are. Thus, there is a need not only to develop short and effective interventions but also to find ways in which such interventions can be delivered/conducted with caregivers at home.

A 12-week structured psychosocial support group of weekly two-hour sessions was led by two facilitators using an adapted form of Cunningham’s “Healing Journey” program. The intervention included training in relaxation, guided imagery, meditation, emotional expression, and exercises promoting control beliefs and benefit-finding. The prospective design included 10 phases to recruit, and 8–11 women were recruited for each group. Data were collected at baseline and at 4 months (corresponding to the end of the intervention), 6 months, and 12 months.

• The study reported on a sample of women newly diagnosed with breast cancer.
• Women participated in one of three conditions: intervention group (n = 54), standard care group (n = 44), and decliner group who refused the intervention (n = 56).

New Zealand

A quasi-experimental study design was used.

• Cortauld Emotional Control Scale: emotional suppression
• Illness Perceptions Questionnaire–Revised: perceived control
• Perceived Risk of Recurrence: two items, 1–10 scale
• Benefit-Finding Scale for Breast Cancer
• Functional Assessment of Cancer Therapy (FACT): emotional well-being subscale
• Cancer Worry: two items, 1–10 scale
• State-Trait Anxiety Inventory: state anxiety
• Coping Efficacy: measured five items

Repeated measures ANOVAs revealed group differences in state anxiety over the first four months. Scores decreased for intervention participants, but not the standard care or decliner participants. Anxiety decreased overall from baseline to 6 months and from baseline to 12 months. Longitudinal follow-up occurred over 12 months.

• The study had no randomization.
• The study had a high level of decliners.
• The intervention required special training of facilitators to use the program.

Prophylactic platelet transfusion policy

Comparison of platelet usage to nine months preceding intervention

• N = 98
• KEY DISEASE CHARACTERISTICS: Inpatients with hematologic malignancy; all had prolonged pancytopenia; some patients had undergone transplant

• Intervention trial that was nonexperimental, not randomized

• Protocol: less than 10–all, 10–20—bone marrow biopsy, pyrexia greater than 38, coagulation disorder, major bleed; 20–50—major bleed, soft tissue bleed, fresh retinal hem, disseminated intravascular coagulation (DIC), hemorrhagic cystitis; greater than 50—surgery
• Bleeding defined by World Health Organization (WHO) criteria (grade 0: no bleeding; grade 1: petechiae; grade 2: mild blood loss; grade 3: gross blood loss; grade 4: debilitating blood loss)
   

• Less than 10k—13 bleeds
• 10–20k—27 bleeds
• Greater than 20k—117 bleeds (18 DIC and 54 hemorrhagic cystitis); one death with DIC
• Transfusion trigger less than 10k in absence of fresh bleeding and sepsis is safe.
   

• Type of chemotherapy not controlled
• Fifty-four episodes of bleeding were hemorrhagic cystitis
• Bleeding episodes not separated by patient (one patient with 32 episodes)
• Platelet usage was compared, but bleeding was not.
• Rubella et al. (1997) with further support of 10k platelet level

To evaluate the efficacy and safety of transdermal fentanyl in the treatment of mucositis pain associated with chemotherapy

Transdermal fentanyl (TF) was administered at a rate of 25 mcg/hour for adult patients, including those who were opioid naive. In pediatric patients, TF was administered at 12.5 mcg/hour. Because of the delayed effect of TF, patients received IV or subcutaneous morphine to relieve pain during the 8–12 hours after application of the patch. The dose of TF was adjusted after the first 24 hours, according to pain score, until pain was controlled. (Control was defined as a score of 3 or less on the rating scale.) The dose of TF was increased in 25 mcg/hour increments or 12.5 mcg/hour increments, according to age group. Severe breakthrough pain was managed with IV or subcutaneous morphine. All subjects were routinely treated with oral hygiene and antiviral, antibacterial, or antifungal oral agents. The same clinician evaluated patients on the first day of chemotherapy and daily for approximately three weeks. The patient reported pain daily by citing a score on a numeric scale. Mucositis was evaluated, on a daily basis, in terms of National Cancer Institute (NCI) Common Toxicity Criteria (CTC). Study questionnaires were sent to all patients. Questionnaire data were recorded before treatment with TF and 2, 6, and 10 days later.

• The sample was composed of 32 patients.
• Median patient age was 40 years. Age range was 4–76 years.
• Of all patients, 56.3% were female and 43.7% were male.
• The most common diagnoses were non-Hodgkin lymphoma, neuroblastoma, nasopharyngeal cancer, breast cancer, and small-cell lung cancer. Other diagnoses were included in the sample. All patients had a pain score of 4 or higher at study entry. All patients were receiving chemotherapy.

• Multisite
• Outpatient
• China

Open-label prospective trial

• Numeric rating scale (NRS), to measure pain intensity
• NCI CTC, to measure mucositis and adverse events
• European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC QLQ-C30), to measure quality of life

• After chemotherapy, median time to onset of moderate oral mucositis was five days (range of days to onset was 1–16). 
• Prior to use of TF, median NRS pain score was 6. By day 3 and at days 5, 7, 10, and 15, NRS scores had improved significantly (p < 0.001), compared to NRS scores at baseline. By day 3 median NRS was 4; by day 10, median NRS was 2. Pain disappeared in 65.6% of subjects.
• Results as measured by the EORTC QLQ-C30 improved significantly (p < 0.001) in regard to appetite, mental status, sleep, fatigue, and daily life.
• A dose of 25 mcg/hour was sufficient to control mucositis pain in 75% of the sample. Of all patients, 18.8% developed nausea and vomiting, 15.6% reported dizziness, 15.6% reported stomach discomfort, 6.3% reported constipation, and 6.3% reported patch-related itching.
• No patients discontinued the drug because of toxicity.

In this study, transdermal fentanyl was effective in reducing pain and improving quality-of-life parameters in the sample specified. Transdermal fentanyl was associated with a relatively low prevalence of adverse effects.

• The study had a small sample, with fewer than 100 patients.
• Authors did not state whether any patients required use of medication for breakthrough pain.
• Authors did not report the prevalence of adverse effects by severity.
• The number of pediatric patients versus adult patients was not stated. The means by which authors measured the pain and quality of life of very young patients (some as young as 4 years old) was not reported.
• Other mechanisms for the management of oral mucositis, which could be expected to influence pain, were not controlled or fully described.

Authors noted the delay of onset with TF opioid use. This delay suggests that TF therapy begin before onset of significant levels of pain. Further well-designed studies of TF, in adults and children, are needed.

• Ifosfamide 1800 mg/m² for five days, carboplatin 400 mg/m² for two days, and etoposide 100 mg/m² for five days with recombinant human interleukin-11 (rhIL-11) subcutaneous (SC) at 25–125 mcg/kg/day on days 6–33
• Chemotherapy repeated every 21 + days or when hematologic recovery was achieved (absolute neutrophil count greater than 100z10/9 and platelet count greater than 100x10/9 for two days without platelet transfusion or a maximum of 28 days). No chemotherapy dose change was permitted in cycles one and two.
• For six cycles, until tumor progression or inadequate hematologic recovery by day 60 in cycle one or day 35 in subsequent cycles
• Select patients who received rhIL-11 with six cycles of chemotherapy and who benefited in the investigators’ opinions were able to receive subsequent doses.
• G-CSF was administered SC beginning day six and until post nadir
• Primary endpoints for safety were AE, lab, and radiologic findings.
   

• N = 47
• MEDIAN AGE = 10.5 years
• AGE RANGE = 8 months–24 years
• MALES: 30, FEMALES: 17
• KEY DISEASE CHARACTERISTICS: Children, adolescents, and young adults with solid tumors or lymphoma
• OTHER KEY SAMPLE CHARACTERISTICS: 53% white; three weeks since last chemotherapy and six weeks since last nitrosourea chemotherapy. Excluded primary/mets intracranial tumors greater than 50% infiltration of tumor into bone marrow, craniospinal xRT or xRT greater than 50% of bone marrow space
   

• Phase I/II dose escalation study

• Dose-limiting toxicities include grade 4 nonhematologic toxicity or papilloedema.
• Tolerated dose defined as dose level at which no more than 1 of 10 patients experienced dose-limiting toxicity
• Serum IL-11 concentrations measured at genetic institute
• Blood collected at 0 (predose),1, 2, 2.5, 3, 4, 6, 8,10,12, and 14 hours after IL-11
• Pharmacokinetic measures done
• Progenerator cells evaluated by colony formation assays as well as flow
• Cytokine receptor expression measured by flow
• Primary endpoints for safety were AE, lab, and radiologic findings.
• Secondary objectives to evaluate and estimate hematologic responses

Three of 47 patients withdrew. Also, 24 of 44 discontinued before receiving two cycles (9 because of disease progression; 3 for adverse events [papilloedema]; 2 for therapy changes; 10 for other reasons; 1 died). Twenty patients completed two cycles of therapy. Median time to platelet recovery was reduced (24.5–20 days in similar historical cohort). One patient developed incidence of anti-IL-11 antibody formation. Number of platelet transfusions was three versus six in historical controls. IL-11 was well-tolerated at doses less than 50; the maximum tolerated dose is 50 mcg/kg/day. Doses above this increased side effects of papilloedema in 6 of 26 patients, periosteal bone changes in 4 of 26 patients, and cardiomegaly.

• Dose-limiting side effects at greater than or equal to 75 mc
• Tachycardia—45%
• Conjunctival infection—45%
• Edema—29%
• Pain—23%
• Rhinitis—20.5%
• Diarrhea—20.5%
• Cardiomegaly—20.5%
• Papilloedema—16%
• Periosteal bone changes—11%
• Small N
• Follow-up one year out
• Large range in age/size
• Not randomized—compared to historic controls