To provide information about patterns of granulocyte colony-stimulating factors (G-CSF) use in Spanish oncology clinical practice and to compare neutropenia-related outcomes in patients treated daily with G-CSF with patients receiving nondaily G-CSF (pegfilgrastim)

Medical records were reviewed for data collection and analysis of outcomes in patients who received pegfilgrastim compared to those who received daily G-CSF.

• N = 391 patients from 34 participating centers 
• AGE: Older than 18 years
• MALES: 46.4% in daily G-CSF group, 31.8% in pegfilgrastim group  
• KEY DISEASE CHARACTERISTICS: Solid tumors excluding breast
• OTHER KEY SAMPLE CHARACTERISTICS: Had chemotherapy with at least one concomitant G-CSF administration more than two months prior; 79.3% had stage 3 or 4 disease

• SITE: Multi-site
• SETTING TYPE: Outpatient
• LOCATION: Spain

• PHASE OF CARE: Active treatment

• Retrospective, multi-center, observational
  • Each investigator reviewed the most recent charts of five patients treated with daily G-CSF and of another five most recently treated with pegfilgrastim.

• Percentage of patients with grade 3 or 4 neutropenia (absolute neutrophil count [ANC], .0 x 10⁹/L) and incidence of febrile neutropenia (FN), defined as ANC 0.5 x 10⁹/L and temperature 38°C or higher during the same day
• Percentage of patients experiencing dose delays (more than three days during any cycle) and dose reductions (less than 84% of planned dose)
• Percentage of patients with dose intensity was 85% or higher (defined as 85% or more of planned dose for all agents in regimen and three days or less of dose delay)
• FN-related hospitalizations and response to chemotherapy—complete, partial, or nonresponse per physician’s criterion

In the multivariate analysis following adjustment for possible confounding factors, a significantly higher risk (OR 1.73, 95% CI 1.004–2.97) of severe neutropenia was associated with daily G-CF versus pegfIlgrastim. The patient group receiving daily G-CSF had a 73% higher probability of grade 3 or 4 neutropenia. Patients receiving daily G-CSF experienced a greater number of dose reductions (38.4% versus 31/6%, p = 0.116) and delays (54.7% versus 41.7%, p = 0.013). Chemotherapy dose intensity of less than 85% also was greater in the daily G-CSF group (39.4% versus 28.9%,p = 0.030). Response rates also were lower in the daily G-CSF group. Complete responses were 17% for daily G-CSF versus 26.4% for the pegfilgrastim group (p = 0.028) and partial response was 41.2% for daily G-CSF versus 52% for the pegfilgrastim group (p = 0.009), again demonstrating better response in the pegfilgrastim group. The two main adverse reactions reported were bone pain and asthenia, with a higher incidence noted in the daily G-CSF group (6.2% versus 1.7%, p = 0.025). Patients receiving at least five days of daily G-CSF, versus those who received fewer than five days, experienced better outcomes.

G-CSF and pegfilgrastim can reduce the incidence and adverse outcomes of treatment-related neutropenia. If G-CSF is stopped prematurely, the efficacy is compromised. This study demonstrates that G-CSF often is initiated later than recommended following chemotherapy, and patients receive fewer days per cycle than required for optimum efficacy.

• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement validity/reliability questionable

Daily G-CSF and pegfilgrastim are used prophylactically to reduce grade 3 or 4 neutropenia, incidence of FN, dose delays and reductions, and FN-related hospitalizations, and to increase response to chemotherapy, measured as complete, partial, or nonresponse per physician’s criterion. Suboptimal dosing is more prevalent with daily G-CSF because of starting later than recommended following myelosuppressive chemotherapy and stopping too early.

To test the feasibility of providing a psychoeducational intervention for people with head and neck cancer.

The NuCare coping strategies program used a self-study book and audiocassette designed to enhance personal control and teach emotional and instrumental coping responses. It consisted of training in problem solving, relaxation, coping skills, goal setting, communication, social support, and lifestyle factors. Three participants chose to receive it in a small group format, 33 chose one-on-one sessions with a therapist, and 23 chose a home format with no therapist. The outcomes measured were quality of life (QOL), anxiety, and depression.

• The study was comprised of 66 patients with head and neck cancer; 59 completed the program and 50 gave outcome data.
• No age, gender, race, or ethnicity demographics were provided.

The study was conducted at the head and neck oncology outpatient clinic of the Montreal Jewish General Hospital, Quebec, Canada.

Patients were undergoing the active treatment phase of care and were evaluated at baseline and three-month follow-up.

This was a prospective, nonrandomized, one-group, feasibility study.

The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLC-C30) was used to measure QOL and sleep.

Patients reported improvement in physical and social functioning and global QOL, sleep disturbance, fatigue, and depressive symptoms.

• Patients were able to choose which format was used.
• The pilot study was not designed to test the effectiveness of the intervention.
• Special training of the research nurse was required.
• There was no cost to patients.

Participants were offered the Nucare coping strategies program (teaches people to cope with cancer, based on the McGill Model of Nursing) in one of three formats:  small group; one on one; and one on one with therapy (home version with materials).  There was no control arm.  Data were taken at baseline and two and three months following the intervention outcome.  Participants chose the study arm.

• Fifty-nine participants completed the study, and there were outcomes data for 50.
• Gender, race, and income were not described. 
• Participants had head and neck cancer.

This was a nonrandomized, no control pilot, feasibility study for delivery in which participants wanted the intervention.

European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30)

Fatigue was improved in 17 (38%) patients overall, and improvement was equal in self (home) to that seen with the use of a therapist.

• Only one cancer group was studied.
• There were costs associated with the use of a therapist.

The objective of this study was to compare the efficacy of supplemental, oral, and parenteral opioid doses consisting of either 25% or 50% of the equivalent 4-hour opioid dose (i.e., total 24-hour opioid dose divided into 4-hour portions) in patients already receiving opioids on a regular basis.

The study reported on a sample of 33 terminally ill patients with cancer and dyspnea at rest who already were receiving opioids.

The study was conducted in three separate palliative care centers in Quebec, Canada.

The study was a randomized, double-blind, continuous sequential controlled trial.

Dyspnea intensity on the visual analog scale and respiratory rate were measured at baseline, 30, 60, 120, 180, and 240 minutes after dose.

The overall treatment effect, as measured by dyspnea intensity and respiratory frequency, was not significantly different for 25% or 50% of the equivalent four-hour opioid dose. A significant (p < 0.0001) decrease was found in pre- and post-dyspnea intensity. Dyspnea decrease was inverse to baseline dyspnea intensity (i.e., low dyspnea at baseline had greater decrease in dyspnea intensity whereas high dyspnea at baseline had less decrease).

• Authors reported that the sample required one more pair to offer definitive preference in favor of 25% of the four-hour dose.
• The finding was restricted to those already receiving regular opioids.
• The study was properly designed and conducted at multiple sites; however, the sample was limited.

Because 25% and 50% doses had the same effect, a supplementary dose of 25% of the equivalent four-hour opioid dose is recommended to reduce dyspnea for as long as four hours.

To assess the efficacy and safety of an intrathecal (IT) combination of ziconotide and morphine in malignant pain refractory to high doses of oral uploads

Visual anolog scale of pain intensity (VASPI) scores and Karnofsky Performance Status Scale (KPSS) scores were recorded for each patient at the initial visit. An IT catheter was place under fluoroscopy with aseptic technique, with a 1 g dose of cefazolin to prevent infection. Patients continued their long-term oral morphine until the IT infusion started and asked to start a short-acting morphine dose of 10 or 30 mg if needed. VASPI and KPSS scores, vital signs, electrocardiograms (ECGs), and adverse events were evaluated at day 2, day 7, and weekly up to day 28. The ziconotide infusion titration was started at 2.4 micrograms per day and increased by 1.3 micrograms per day at day 7 in patients with a VASPI score greater than 30 at rest. IT morphine dose was calculated based on their daily dose, an oral-IT ratio of 400:1. Increases in IT morphine were based on the oral morphine consumption. Doses were adjusted for adverse events and analgesic effect. The mean VASPI score, mean change in VASPI score, and mean percentage change from baseline to each visit and to the last observation was calculated.

• N = 20   
• AGE = 18 years or older
• MALES: 35%   
• FEMALES: 65%
• KEY DISEASE CHARACTERISTICS: Disseminated cancer with bone metastasis involving vertebral bodies
• OTHER KEY SAMPLE CHARACTERISTICS: Participants had to have pain related to malignancy, prevalently nociceptive pain, a VASPI score greater than 70 mm at rest, or an occurrence of adverse events. Patients were excluded if they showed signs of sepsis or inadequately treated infection; uncontrolled heart failure; second-degree heart block; third-degree heart block; or history of dementia, delirium, hysteria, or untreated affective disorder.
   

• SITE: Single site   
• SETTING TYPE: Inpatient setting   
• LOCATION: Pain Centre at Italy Bari Policlinico Hospital, Bari, Italy

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Late effects and survivorship; end-of-life and palliative care
   

• Prospective, observational study
  • Used repeated measures

• KPSS
• VASPI
• Vital signs: blood pressure, heart rate, respiratory rate, and temperature
• 12-lead ECG
• Adverse events: Coding Symbols for Thesaurus of Adverse Reaction Terms (5^th ed.)
   

Prior to the study, participants had persistent pain for a mean of six months SD = two months) and took a mean daily dose of 320 mg per day (SD = 80 mg) of systemic opioids. The mean VASPI score at rest was 90 mm (SD = 7 mm), with a mean incidental VASPI score of 99 mm (SD = 3 mm), and a mean KPSS of 59 (SD = 10. 4). Patients had severe opioid-related side effects that did not permit an increase in systemic opioids. IT therapy started with morphine 0.82 mg per day (SD = 0.36 mg) with ziconotide 2.4 mcg per day. On day 2, the mean VASPI score at rest decreased to 55 mm (SD = 12 mm), a significant reduction (p < .001). For five patients, an increase in morphine was necessary. On day 7, the mean VASPI at rest was 44 mm (SD = 11 mm), a significant decrease (p < .001). Four patients had an increase in ziconotide daily. On day 28, mean VASPI was 34 (SD = 13), a significant decrease (p < .001). Eighty percent of patients reached the effective dose for morphine and ziconotide within two weeks. Only five patients survived until the third month with good pain control. The maximum dose of ziconotide was 5.2 mcg per day, and the maximum dose of morphine was 2 mg per day. Four patients developing adverse effects attributed them to the study drugs. Changes in serum creatinine kinase levels and vital signs were not significant. No infections correlated with IT catheter placement.

IT therapy with ziconotide and morphine is a helpful strategy in controlling malignancy-related pain refractory to high dose of systemic uploads. Using both drugs appears to have a synergistic effect and may benefit patients with cancer. Lower doses of each drug may be utilized with few adverse events and side effects. However, this study has a few limitations that impair generalizability, may have a potential for bias, and may not have captured the risk to patients being treated longer than a few months.

• Small sample (less than 30)
• No control group or comparison (potential for bias)
• No randomization, no blinding
• Sample size was 20 (less generalizable).
• Only five patients survived to three months.
• Oservation was limited to one month.
• The sample was small and the length of observation was limited, so observable adverse events and complications may have not been observed.

Combination IT ziconotide and morphine in patients with cancer with nociceptive bone pain refractory to systemic opioids may be a helpful strategy for controlling pain. Low doses of ziconotide are required with the use of morphine, as compared to higher doses of ziconotide alone. In turn, less adverse events may be observed with potentially better pain control. When considering drug stability, alternative agents for pain in combination with ziconotide may be considered in place of morphine, as pump refills are required with lower-stability agents.

To determine if a multimodal exercise program for patients during induction chemotherapy is feasible, safe, and beneficial for fatigue, quality of life, and fitness

Patients were randomized to the exercise or usual care groups. Usual care generally included suggestions to walk on a regular basis, without further instruction. Those in the exercise group were approached 4–5 days per week during hospital admission to participate in light-to-moderate–intensity exercise for 30–60 minutes. Exercise sessions included combined aerobic, resistance, and flexibility training. Aerobic intensity was encouraged at an exertion equivalent to 50%–75% of heart-rate reserve. The resistance exercises targeted large muscle groups using resistance bands and free weights. Flexibility was incorporated into each session via static stretching. Exercise sessions were directly supervised by a certified exercise physiologist. Study assessments were completed at baseline, post induction, and within two weeks of discharge, post cycle 2 (4–6 weeks post discharge).

• N = 70 post induction; 63 completed post-consolidation measures.
• MEAN AGE = 57 years (SD = 14.7)
• MALES: 54.3%, FEMALES: 45.7%
• KEY DISEASE CHARACTERISTICS: Patients with acute myeloid leukemia (AML) or relapsed AML receiving induction chemotherapy who were medically cleared for participation
• OTHER KEY SAMPLE CHARACTERISTICS: Participants in the exercise group were slightly older.

• SITE: Single site  
• SETTING TYPE: Inpatient    
• LOCATION: Canada

• PHASE OF CARE: Active antitumor treatment

• Randomized, controlled trial

• European Organization of Research and Treatment of Cancer Core Quality of Life (EORTC QLC-C30)
• Functional Assessment of Cancer Therapy-Fatigue (FACT-F) subscale/BMI
• Maximal oxygen consumption test (VO₂ max test)
• Six-minute walk test (6MWT)
• Grip strength
• Daily exercise diary for control patients

Exercise group participants completed 514.2 minutes of exercise on average during an average admission of 36.5 days. The most common reported reason for not exercising was fatigue. Adherence to exercise sessions was 54%. Control group patients exercised an average of 510.4 minutes over 35.8 days. Participants in both groups demonstrated an improvement in global quality of life. Fatigue scores improved only in the exercise group, with a between group difference of 3.6 points, which was not statistically significant. The six-minute walk improved in both groups but improved significantly more in the exercise group (p = 0.005). No significant adverse event occurred. During over 1,000 patient days of observation, four musculoskeletal events were reported. No differences existed between groups in length of stay or other resource utilization.

This study demonstrated that the provision of an exercise program is feasible for patients during induction chemotherapy and may help manage fatigue in these patients. Patients who participated in the multimodal exercise program demonstrated improved physical fitness.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Given the comparison of mean hours of exercise between study groups, the total amount of physical activity did not appear substantially different between groups, which may have affected the lack of substantial differences in fatigue.

Participation in an exercise program of moderate intensity was shown to be feasible for patients who were hospitalized and receiving induction chemotherapy for AML.

To examine the feasibility (recruitment, retention, and adherence), preliminary efficacy, and safety of a 12-week, home-based exercise program for middle-aged and older acute myeloid leukemia (AML) survivors

• N = 40  
• AVERAGE AGE = 56 years
• MALES: 45%, FEMALES: 55%
• KEY DISEASE CHARACTERISTICS: Acute myeloid leukemia; the average time from diagnosis to study enrollment for all participants was approximately two years.
• OTHER KEY SAMPLE CHARACTERISTICS: Participants were mostly white. The mean body mass index (BMI) 28.25%. Patients had undergone posthematopoietic stem cell transplant.

• SITE: Single-site    
• SETTING TYPE: Multiple settings    
• LOCATION: Home and “health care” gym

• PHASE OF CARE: Transition phase after active treatment
• APPLICATIONS: Elder care  

Phase II randomized controlled trial with an exercise group and a wait-list control group that could cross over to the exercise group at week 12.

• Primary outcome measures included both global quality of life (QOL) and fatigue.
• QOL was measured with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30).  
• Functional Assessment of Cancer Therapy–Fatigue (FACT-F)
• Secondary outcome measures included the Edmonton Symptom Assessment Scale (ESAS).

Recruitment and retention rates were 31% and 91%, respectively. The adherence rate was 28%. The analyses did not suggest statistically significant or clinically important benefits in QOL, fatigue, or physical fitness between groups. There were no adverse events.

Successful recruitment with low adherence and limited effects on clinical outcomes including fatigue.

• Small sample (< 100)
• Risk of bias (no blinding)
• Measurement/methods not well described
• Other limitations/explanation: The description of the cross-over of patients from the control group is confusing and inconsistently described from the actual protocol.

Further study is needed in this population including how to enhance exercise adherence.

To evaluate the effectiveness of colloidal oatmeal lotion (Aveeno^®), administered TID for at least seven days.

• The study reported on a sample of 10 patients.
• Patients were receiving epidermal growth factor receptor–inhibitor (EGFRI) and tyrosine-kinase inhibitor (TKI) therapy (e.g., cetuximab, erlotinib, panitumumab, sorafenib) and were experiencing cutaneous reactions.

Multiple centers in Washington, DC, and New York, NY

This was an open-label study used to evaluate the rate and quality of response to colloidal oatmeal lotion.

Toxicity was graded as follows.

• Grade 1: asymptomatic, erythematous rash
• Grade 2: rash plus itching
• Grade 3: confluent lesions and tenderness
• Grade 4: deep ulcerations and exfoliative or severe xerosis

• Ten of 11 patients were evaluable.
• Six patients had a complete response and four had a partial response; therefore, the response rate was 100%.
• Responses occurred from six to 10 days after initiation of colloidal oatmeal lotion.

Treatment with colloidal oatmeal lotion appeared to be effective in controlling rash associated with EGFRIs and multiple TKIs. This treatment allowed for the continuation of antineoplastic therapy.

• This was a small, nonrandomized, open-label study.
• The description of the measurement tool or method used to grade rash symptoms was inadequate; reliability and validity were unclear.

To evaluate the short- and long-term effects of ropivacaine wound infiltration on pain after breast cancer surgery

Patients were randomized to receive, prior to surgery, either ropivacaine or normal saline placebo wound infusion. All patients received the same general anesthesia regimen of propofol and sufentanil. At the end of surgery, before skin suturing, the wound was completely infiltrated along the subcutanous and deep layers of the breast and axilla surgical incisions. Infiltration was also done in the second and third intercostal spaces. The ropivacaine group received 3 mg/kg of 0.375% ropivacaine. Pain was assessed every 30 minutes for two hours in the postanesthesia care unit and every six hours for the next 48 hours. Patients completed study questionnaires at baseline and at 3, 6, and 12 months after surgery.

• The sample was composed of 236 patients.
• Mean patient age was 56.5 years.
• All patients were female.
• All patients were undergoing surgery for breast cancer; 45%–52% had breast-conserving surgery with axillary node dissection, and 40%–45% had mastectomy with either axillary or sentinel lymph node dissection.

• Single site
• Multiple settings
• France

Mutliple phases of care

Randomized double-blind placebo-controlled trial

• Visual analog scale (VAS) to assess pain
• Brief Pain Inventory
• Hospital Anxiety and Depression Scale

• During the first 90 minutes, with patients at rest and with movement, VAS pain scores were lower in the group that received ropivacaine (p < 0.001) than in the control group.
• Over the first 48 hours in the ropivacaine group, 73% reported no pain at rest and 53% reported no pain during movement. Over the first 48 hours in the control group, 53% reported no pain at rest and 48% reported no pain during movement (p < 0.001).
• In the first 48 postoperative hours, authors noted no differences between groups in regard to morphine consumption.
• At 3, 6, and 12 postoperative months, authors noted no differences between groups in regard to pain scores.

Surgical wound infusion with ropivacaine resulted in significantly lower acute postoperative pain as measured up to 48 hours after breast cancer surgery. Wound infusion had no effect on longer-term postoperative pain.

Authors did not describe chronic levels of pain at follow-up time points.

Local wound infusion resulted in significantly lower acute postoperative pain after breast cancer surgery. This study adds to the body of evidence that demonstrates the effectiveness of this approach. Nurses can advocate for this approach to help ensure that surgical patients receive effective acute pain management.

STUDY PURPOSE: To examine the efficacy of chemoprotective agents to prevent or limit neurotoxic side effects of cisplatin and related chemotherapy agents

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 20 
• TOTAL PATIENTS INCLUDED IN REVIEW = 2459
• SAMPLE RANGE ACROSS STUDIES: 18–755
• KEY SAMPLE CHARACTERISTICS: Varied tumor types receiving platinum-based chemotherapy

PHASE OF CARE: Active antitumor treatment

There is insufficient high quality evidence to show that any agent is protective against platinum-induced neuropathy. There is some suggestion that amifostine, glutathione, and calcium and magnesium may have some effect.

• Limited number of studies included
• Low sample sizes
• There were few studies per intervention, and very few studies with small sample were included in the meta-analyses.

There is insufficient evidence to show that any agent is truly effective in protecting against neurotoxic effects of platinum-based chemotherapy. There is a continued need for well designed research using appropriate objective as well as subjective measures of neuropathy.