To compare the efficacy and safety of granisetron injection extended-release (APF530) versus ondansetron for delayed chemotherapy-induced nausea and vomiting (CINV) after highly emetogenic chemotherapy, following a guideline-recommended three-drug regimen

Patients receiving highly emetogenic chemotherapy were randomized into either the APF530 or ondansetron arm for the study. Patients in the APF530 arm received APF530 500 mg subcutaneously and saline placebo in place of ondansetron. Patients in the ondansetron arm received ondansetron 0.15 mg/kg intravenously and a saline placebo subcutaneously in place of APF530 on day 1. All patients also received fosaprepitant 150 mg IV and dexamethasone 12 mg IV on day 1; dexamethasone 8 mg orally once daily on day 2 and twice daily on days 3–4. A topical anesthetic was applied to the injection site before APF530 or its placebo were administered. On day 1, all study medications were administered 30 minutes before the start of chemotherapy.

• N = 902   
• MEAN AGE = 55.7 years and 55.6 years for the APF530 and placebo arms, respectively
• MALES: 20.4% and 17.5% of patients enrolled in the APF530 and placebo arms, respectively; FEMALES: 79.6% and 82.5% of patients enrolled in the APF530 and placebo arms, respectively
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: No specific tumor types were recruited.
• OTHER KEY SAMPLE CHARACTERISTICS: Men and women aged 18–80 years receiving the first cycle of a single-day highly emetogenic chemotherapy for a histologically or cytologically confirmed malignancy

• SITE: Multi-site   
• SETTING TYPE: Not specified    
• LOCATION: Seventy-seven medical centers across the United States

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Elder care

• Prospective, randomized, double-blind, double-dummy, parallel-group, multicenter, phase-III trial

Patients were monitored during four clinic visits:

• screening: day –21 to –1
• baseline/day 1 
• day 6 
• final safety follow up on the day of the patient’s next chemotherapy administration

Patients completed symptom diaries during days 1–6 to self-report nausea, vomiting, retching, and rescue medication usage.

A higher percentage of patients receiving APF530 had delayed-phase complete response when compared to patients receiving ondansetron. The absolute treatment difference was 8% (95% CI [1.7, 14.4], p = 0.014). Delayed-phase CR rates for the cisplatinum arm were 65.3% with the APF530 regimen and 54.7% with the ondansetron regimen. The absolute treatment difference here was 10.6% (95% CI [–1.4, 22.7]). For the non-cisplatinum arm, the delayed-phase CR rates were 64.4% for APF530 and 57.4% for ondansetron regimens. This absolute treatment difference was 7% (95% CI [–0.9, 12.1], unadjusted p = 0.092).

APF530 provided superior control of delayed-phase CINV after highly emetogenic chemotherapy when compared with standard three-drug regimens.

• Short follow-up time

APF530 was found to be a well-tolerated  extended-release granisetron formula with clinical benefit for the control of CINV after highly emetogenic chemotherapy.

To compare treatment with topical 0%–1% methylprednisolone versus 0%–5% dexpanthenol and historical controls in a cohort of patients undergoing fractionated radiation therapy

After obtaining baseline data on an initial control cohort of untreated patients (n = 15), a subsequent cohort of patients was randomized to either 0%–1% methylprednisolone aceponate cream or 0%–5% dexpanthenol cream. Patients were instructed to apply the assigned cream twice daily from initiation of radiation therapy and for a two-week period after completion. No other topical medications, emollients, or powders were used during this period.

• The study sample was comprised of historical controls as well as patients using methylprednisolone aceponate cream (n = 10) and patients using dexpanthenol (n = 11).
• Mean age of the methylprednisolone group, dexpanthenol group, and historical controls was 62, 44, and 55 years, respectively, with a range of 39–75 years, 35–74 years, and 29–75 years, respectively.
• All patients were women with breast cancer.

The study took place at the University of Innsbruck in Austria.

The study used a prospective randomized double-blind study design with comparison to historical controls.

• Patients were assessed immediately prior to initiation of radiation therapy and weekly thereafter or erythema, desquamation, erosion, induration, and hyperpigmentation on a four-point scale: none (0) to severe (3). The total clinical score was a sum of individual ratings.
• To assess the impact of radiation therapy on epidermal barrier function, transepidermal water loss was measured weekly over four different areas within the irradiated field (one test per quadrant) and over one control area on the volar forearm using an evaporimeter.
• Recordings were not taken over skin showing extensive erosions.
• Quality of life was measured at the beginning of radiation therapy and after completion of the follow-up period to evaluate skin-specific (Skindex) and general outcome measures (SF-36).

Comparison of treatment groups with the historical, untreated control group suggested that either of the two topical regimens was superior to no treatment with respect to transepidermal water loss measurements, but not statistically significant. Transepidermal water loss levels did not differ between patients who received adjuvant chemotherapy and those who did not. There were no differences in quality-of-life findings. No quality-of-life data were obtained from untreated individuals in the preliminary cohort group. Skindex scores showed appearance of radiation dermatitis in virtually all participants. The dexpanthenol group showed deterioration that reached statistical significance for dimensions of depression, embarrassment, discomfort, and limitations (p < 0.05).

Prophylactic and ongoing use of topical therapy with topical corticosteroid or dexpanthenol-containing emollient does not prevent radiation dermatitis.

• The study sample was small.
• The 36-SF has been used to assess qualityo f life in patients with acne and psoriasis but not patients with radiation dermatitis.
• Skindex has been used to assess quality of life in a variety of dermatologic conditions, but not specifically used for radiation dermatitis.
• Median age of patients vary by 18 years, with an older median in methylprednisolone group.
• Scale for dermatitis grading is difficult to compare to standard scales used for radiation therapy-induced dermatitis.

To compare the effectiveness of adding an aprepitant regimen to an ondansetron and dexamethasone regimen for chemotherapy-induced nausea and vomiting (CINV)

Patients were randomized to receive the treatment arm (aprepitant, ondansetron, and dexamethasone on day 1; aprepitant and dexamethasone on days 2–3; dexamethasone on day 4) or the control arm (ondansetron plus dexamethasone on days 1–4).

The study looked at 489 patients with solid malignancies receiving chemotherapy (patients were cisplatin-naïve). The treatment arm had 231 participants, and the comparison group had 229 participants.

The study was a prospective, randomized, double-blind trial with sponsor blinding.

Measurement instruments were

• Patient diaries used to record number of episodes of vomiting
• Use of rescue medication
• Nausea visual analogue scale (VAS).

Patients were considered treatment failures if they needed to take rescue medication.

• Complete response (CR) was defined as no vomiting and no rescue medication in the overall period (days 1-5 after cisplatin infusion).
• The aprepitant regimen was superior to the control arm in the overall treatment period (CR = 72% versus 61%, p = 0.003).
• No significant difference was observed among groups in control of nausea.
• The aprepitant group had higher rates of drug-related adverse events.

Efficacy might be further improved if ondansetron is given on days 1-4 as well (as per guidelines), rather than only on day 1 as done in this study.

The addition of aprepitant to prevention of CINV provides an objective improvement in control of vomiting as compared to ondansetron and dexamethasone alone; however, the triple-drug combination is recommended for practice.

To assess the effects of controlled weight lifting for breast cancer survivors with lymphedema

For the first 13 weeks, participants in the intervention group received supervised 90-minutes session twice weekly led by certified fitness professionals employed by the fitness centers, who received three days of training. There was no upper limit on weight lifting. Participants were given a custom-fitted compression garment at 6 and 12 months and were required to wear the garments during weight lifting.

• The study sample (N = 130) was comprised of female patients who had a history of unilateral, nonmetastatic breast cancer 1–15 years before the study.
• Patients were included in the study if they had a body mass index of less than or equal to 50, at least one lymph node removed, and clinical diagnosis of stable breast cancer-related lymphedema.

The study took place at community fitness centers near participants' homes in Philadelphia, PA.

The study used a randomized controlled trial design.

• Lymphedema was measured using water volume displacement.
• Percentage body fat was measured.
• Physical activity level was measured using metabolic equivalent of task.

Weight lifting did not significantly affect the severity of breast cancer-related lymphedema. Weight lifting reduced the number and severity of arm and hand symptoms, increased muscular strength, and reduced the incidence of lymphedema exacerbation. Median attendance at exercise sessions was 79%. The proportion of women who experienced at least 5% increase in limb volume was 17% in the control group and 11% in the weight lifting group. Among women who had five or more lymph nodes removed, 7% in the weight-lifting group and 22% in the control group had more than 5% increase in limb volume.

The results of this study should reduce concerns that weight lifting will worsen arm and hand swelling with lymphedema in breast cancer survivors.

• Evaluations for exacerbations were not completed by a single therapist, although the six lymphedema therapists followed a standardized algorithm for evaluation.
• The study had no blinding.

Nurses need to review current handouts and information regarding exercise therapy. The findings of this study support the potential benefits of a slowly progressive weight-lifting program, with appropriate use of compression garments and close monitoring for arm and hand swelling.

To synthesize the literature on the safety and efficacy of exercise training during and after cancer treatment and provide guidelines for exercise for patients with and survivors of cancer. Adults with cancer during and after adjuvant cancer treatment were addressed. The guidelines state that the focus is on sites where the most evidence exists:  breast, prostate, colon, hematologic, and gynecologic cancers.

Evaluation of evidence was based on categories from the National Heart, Lung and Blood Institute (A–D levels). Panel member reviews were presented and discussed at the roundtable, and guidelines were developed by consensus. Specific strategy and terms were not described. Guidelines were developed by an expert roundtable in which members were asked to review relevant literature. The guidelines were limited to an adult population and provided an overview of a volume of evidence in multiple outcome areas related to exercise.

A comprehensive and detailed set of guidelines for exercise approaches applicable for survivors of  breast, prostate, colon, hematologic, and gynecologic cancers was provided in the guidelines, as well as some of the issues of exercise training timing related to phases of care. The guidelines also provided a summary of evidence used per cancer site and identified gaps in research because of the small number of studies in some cases and small sample sizes in many of the studies.

Recommendations for exercise testing were as follows:

• Evaluate for peripheral neuropathies, musculoskeletal morbidities, and fracture risk in those who have received hormonal therapies.
• Assess for risks associated with bone metastases and cardiac risks.
• In patients with breast cancer, evaluate arm and shoulder morbidity prior to upper-body exercise.
• In patients with prostate cancer, evaluate muscle strength and wasting.
• In patients with colon cancer, check for infection prevention behaviors for existing ostomy.
• In patients with gynecologic cancers, evaluate for lower-extremity lymphedema prior to vigorous aerobics or resistance; in patients with morbid obesity assess for safety.
• Exercise testing before walking, flexibility, or resistance training is not required.
• In survivors with or at risk for lymphedema, one repetition maximum testing is safe.

Recommendations for exercise prescription were as follows:

• Allow adequate healing time after surgery (may be as much as eight weeks).
• Resolve arm or shoulder problems with patients with breast cancer before upper-body training.
• Swelling or inflammation in gynecology cases should be resolved before exercise training. 
• Patients with ostomies should have doctor permission before contact sports and weight training.
• Changes in symptoms are reasons to stop an exercise program.
• Patients with bone metastases may need to alter exercise intensity, duration, and mode because of fracture risk.
• Specific cancer site–related recommendations are provided for injury prevention and emergencies.

General activity guidelines were as follows:

• Avoid inactivity.
• Aerobic exercise recommendations are the same as general age-appropriate national guidelines.
• Resistance training should be supervised for at least 16 sessions for patients with breast cancer.
• Patients with radical prostatectomy should also perform a pelvic floor exercise with resistance training.
• Resistance training is more important than aerobics for patients who have received transplants.
• Resistance training should be used with caution in patients with lower-limb lymphedema.
• Age-appropriate flexibility training should be followed.
• Ostomies require avoidance of excessive intra-abdominal pressure.
• Research gaps and recommendations were outlined for yoga, sports, Pilates, and other exercises.
   

No participant associations were described.

The guidelines concluded that there was consistent evidence that exercise is safe during and after cancer treatment, with consideration of specific risks that are associated with various types. Exercise training can be expected to improve aerobic fitness, muscular strength, quality of life, and fatigue. Resistance training can be performed safely in patients with and at risk for lymphedema with breast cancer. Some exercise is recommended for all types of patients. Further study is needed in the areas of dose-response effects of exercise training. The guidelines provided additional evidence-based and expert support for the incorporation of various types of exercise in the care of patients with cancer during and after adjuvant treatment. Continued research is needed in this area in terms of research in other cancer types and determination of dose-response relationships for various outcomes.
 

To evaluate the onset of lymphedema after a one-year weight-lifting intervention versus no exercise among breast cancer survivors at risk for lymphedema

Patients were randomized to the weight-lifting intervention group or control group, who were to have no change in level of exercise. The weight-lifting intervention included a gym membership and 13 weeks supervised instruction with a remaining 9 months unsupervised. Specific equipment varied but provided upper-body exercises (i.e., seated row, supine dumbbell press, lateral or front raises, bicep curls, triceps pushdowns) and lower-body exercises (i.e., leg press, back extension, leg extension, and leg curl), 3 sets of 10 repetitions. Weights were increased for each exercise by the smallest possible increment after two sessions of completing 3 sets of 10 reps with no change in arm symptoms. Trainers called patients who missed more than one session per week. Those who missed two consecutive sessions were asked to reduce resistance and rebuild per protocol. All participants in the intervention or control group who developed lymphedema were given a custom compression garment and were required to wear garments during weight-lifting sessions. Certified fitness professionals employed by the centers received a three-day training course regarding exercise protocol and overview of lymphedema prevention, symptoms, and treatment.

• The study sample (N = 134) was comprised of female patients who had a diagnosis of unilateral nonmetastatic breast cancer one to five years prior.
• Mean age of participants was 54–56 years.
• Patients were included in the study if they
  • Had a body mass index of less than or equal to 50
  • No medical conditions limiting exercise
  • No weight lifting in year prior to study
  • No plans for surgery or absence for a month during the study
  • A stable weight
  • Were not trying to lose weight
  • No prior lymphedema diagnosis
  • No evidence of current lymphedema.

The study took place across multiple community fitness centers in Philadelphia, PA.

The study has clinical applicability for late effects and survivorship.

The study used a randomized controlled equivalence trial design.

• Patients self-reported demographics and treatment history.
• Surgical pathology reports were used to study removed lymph nodes.
• Weight and height (baseline only) were recorded.
• Whole-body dual-energy x-ray absorptiometry scan measured bone mineral density to avoid misrepresenting changes in relative fat mass because of changes in bone density.
• Physical activity outside of weight lifting was assessed using the International Physical Activity Questionnaire.
• Diet was assessed using the Diet History Questionnaire
• Water volume displacement measured lymphedema.
• Clinical laboratory technicians at Penn Therapy used standardized clinical evaluation based on Common Toxicity Criteria version 3.0.
• Participants were sent for evaluation of change for symptoms lasting one week or longer by fitness trainers or if three-month interval measurements by measurement staff indicated a change in treatment-arm volume of at least 5% inter-limb difference.
• Strength was measured at baseline and 12 months based on the maximum amount of weight patients could lift at once.
• Intervention adherence was evaluated by attendance logs kept by fitness trainers.
• Statistical analysis was performed using the Statistical Analysis System (SAS) version 9.2.
   

Women in the weight-lifting group became stronger with lower percentage body fat compared with the no exercise group. Lymphedema onset (5% or more increase in inter-limb volume difference during the 12 months) was 17% (n = 13) in the control group and 11% (n = 8) in the weight-lifting group.

The findings demonstrates that slowly progressive weight lifting will not increase the risk of lymphedema in breast cancer survivors, the primary objective of testing the safety of the weight-lifting intervention. 

• Key sample group differences could influence results.
• Replication to other fitness settings was limited by availability of instructors.
• Patients had limited access to clinical laboratory technicians for immediate evaluation and treatment.
• Garments to be provided to patients was not covered by insurance.

Additional research is needed to determine if weight lifting prevents lymphedema. Nurses should use caution in stating that exercise does not increase onset of lymphedema based on just this study, as it was conducted in a controlled environment, with careful instruction and observation of correct use of equipment and evaluation of arm symptoms and volume changes.

The database searched was MEDLINE through February 2005 to identify intervention studies designed to increase physical activity in adults. Only those studies with a concurrent comparison group with results presented separately for treatment and comparison groups were included.

The quality of 32 studies was assessed using prespecified criteria for internal validity. Twenty-two of 32 studies were rated as being of high methodologic quality and were retained for qualitative and quantitative analysis. The outcomes of physical activity interventions in patients receiving active treatment were analyzed separately from the studies of physical activity after treatment was concluded.

Outcomes were fatigue, health-related quality of life, symptom distress, immune function, hematocrit, body composition, physical exercise capacity (maximal oxygen consumption), and other physical performance measures.

Treatment evaluated aerobic physical activity of moderate to vigorous intensity three to five times per week for 20 to 30 minutes per session. The majority of the interventions lasted between five weeks and three months, with no follow-up at the end of the intervention. The majority of the studies used a control group in which no physical activity or other treatment was prescribed, although a few studies provided an intervention for the comparison group.

• Average sample size for the intervention group was 28 participants.
• The most common diagnosis included in the studies was breast cancer.
• The majority of the studies focused on the time period during or immediately following active cancer therapy. No study focused on palliation.

Although a consistent positive effect of physical activity on fatigue was noted using qualitative study review techniques, effect size calculations revealed no effect of physical activity on fatigue during treatment (weighted mean effect size = 0.13; 95% confidence interval [CI] [-0.06, 0.33]; p = 0.18) or after treatment (weighted mean effect size = 0.16; 95% CI [-0.23, 0.54]; p = 0.43) or on vigor/vitality during treatment (weighted mean effect size = 0.43; 95% CI [-0.07, 0.94]; p = 0.09). A large positive effect of exercise on vigor/vitality posttreatment was noted (weighted mean effect size = 0.82; 95% CI [0.05, 1.6]; p = 0.04). When fatigue and vigor/vitality were combined into one category (under the assumption that fatigue and vitality are the same attribute) and all studies were combined across treatment timing, the weighted mean effect size was still small (weighted mean effect size = 0.19; p = 0.03).

The results supported the conclusion that physical activity has a large positive effect on vigor/vitality after treatment is complete. There is some support from qualitative analysis of a consistent effect of physical activity on fatigue, although the magnitude of this effect may be too small to be clinically meaningful. The study findings also supported a preliminary conclusion that physical activity is generally well tolerated during and after cancer treatment, although the available literature does not allow conclusions to be drawn regarding adverse events from participation.

• The reviewed studies used small, self-selected samples.
• The reviewed studies were heterogeneous in terms of the outcome measures and interventions.
• The reviewed studies had gaps in the level of detail reported about individual study procedures and results.

To evaluate the efficacy of aprepitant plus a standard antiemetic regimen (granisetron plus dexamethasone) in preventing CINV for patients with multiple myeloma receiving high-dose chemotherapy and autologous stem-cell transplantation (ASCT)

Patients randomly were assigned to receive either aprepitant (125 mg orally on day 1 and 80 mg orally on days 2–4) plus granisetron (2 mg orally on days 1–4) and dexamethasone (4 mg orally on day 1 and 2 mg orally on days 2–3) or a placebo plus granisetron (2 mg orally on days 1–4) and dexamethasone (8 mg orally on day 1 and 4 mg orally on days 2–3). High-dose chemotherapy (melphalan 100 mg/m²) was administered on days 1–2, and ASCTs were performed on day 4.

• N = 362
• MEAN AGE = 58.1 years
• MALES: 230 (64%), FEMALES: 132 (36%)
• KEY DISEASE CHARACTERISTICS: Multiple myeloma
• OTHER KEY SAMPLE CHARACTERISTICS: High-dose chemotherapy; receiving ASCT

• SITE: Single site    
• SETTING TYPE: Inpatient  
• LOCATION: Large university hospital in Germany

• PHASE OF CARE: Active antitumor treatment

Prospective, placebo-controlled, randomized, double-blinded, parallel-group, single-center study

• Functional Living Index–Emesis (FLI-E) questionnaire to record quality of life
• Daily diary with a 100 mm Visual Analog Scale (VAS) to record episodes and severity of nausea and vomiting

Patients receiving aprepitant plus standard antiemetic therapy were significantly more likely to achieve complete response (no emesis and no rescue therapy within 120 hours of melphalan administration) (p = 0.0042), were significantly more likely to be without major nausea (p = 0.026) and emesis (p = 0.0036) within 120 hours of melphalan administration, and had a higher quality of life (p < 0.001) compared to the placebo plus standard antiemetic therapy group.

The addition of aprepitant to standard antiemetic therapy resulted in significantly less CINV and a positive effect on quality of life.

The addition of aprepitant to standard antiemetic therapy not only reduced CINV but also improved quality of life for patients receiving ASCT.

IV palifermin 60 mcg/kg per day was given for three consecutive days before chemotherapy cycle A2 or B2 and then for three consecutive days after chemotherapy. All patients received granulocyte colony-stimulating factor (G-CSF). Prophylactic treatment consisted of a number of agents, including tetracaine, chamomile, oral hygiene, and amphotericin B suspensions. Authors used previous studies as historical controls.

This study used a retrospective series of 10 patients with B cell acute lymphocytic leukemia (ALL) or aggressive B cell lymphoma. Patients had World Health Organization (WHO) Oral Mucositis grades of 3 or 4 during cycle A1 or B1 of high-dose methotrexate (HDMTX).

Patients were selected retrospectively from September 2004 to March 2007.

• WHO mucositis grading was obtained daily.
• Opioid use was recorded.

• Sixteen episodes of grade 4 and one episode of grade 3 mucositis were observed without palifermin.
• One episode of grade 4, four episodes of grade 3, and four episodes of grade 2 mucositis were observed with palifermin (p < 0.05).
• IV opioids were reduced from 2,403 mg to 640 mg morphine (p < 0.05).
• Duration of higher grade mucositis was reduced slightly from 12.9 days to 11 days (not significant).

• The sample size was very small.
• Historical controls were used.
• Other prophylactic measures may have had effects.
• No discussion of cost was provided.

To study the safety and effectiveness of training with a mechanical arm crank on lymphedema development after axillary node dissection

Patients were randomized to usual care or supervised training sessions with an arm crank. The training group had exercises for strength and endurance for 60 minutes twice weekly for 12 weeks. The training involved either passive motorized training, motor supported self-training, or training by patient-generated power alone. The training modality used depended on patient performance. Study outcome measures were obtained before and after study-related training.

• N = 49   
• MEAN AGE = 57
• FEMALES: 100%
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: Breast cancer. All underwent axillary node dissection, and the majority had postoperative radiotherapy.

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: Germany

PHASE OF CARE: Late effects and survivorship

Randomized, controlled trial

• Body mass index
• Bioelectric impedance analysis (BIA)
• Arm circumference measurement
• Muscular strength—isometric capacity testing for latissimus dorsi and pectoralis muscles 
• European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-20 (EORTC QLQ C-30)
• Borg scale for effort during training sessions

An increase in lean body mass was observed in patients in the training group (p = 0.017) and decrease in body fat (p = 0.009). Muscular strength increased in both groups. No significant differences existed between groups in arm volume changes. Both groups showed a significant reduction in arm volume from baseline to the end of the study (p < 0.01).

No increase in lymphedema volume was reported with the training provided with the arm crank. This training did not improve lymphedema management compared to usual care.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• No description of usual care

The findings showed no increase in lymphedema with arm training using a mechanical training device. The use of this device appeared to be safe but was no more effective for arm volume reduction than whatever was provided as usual care.