Schnadig, I.D., Agajanian, R., Dakhil, C., Gabrail, N.Y., Smith, R.E., Taylor, C., . . . Vacirca, J.L. (2016). APF530 (granisetron injection extended-release) in a three-drug regimen for delayed CINV in highly emetogenic chemotherapy. Future Oncology, 12, 1469–1481
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.
Patients were monitored during four clinic visits:
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.
APF530 was found to be a well-tolerated extended-release granisetron formula with clinical benefit for the control of CINV after highly emetogenic chemotherapy.
Schmuth, M., Wimmer, M.A., Hofer, S., Sztankay, A., Weinlich, G., Linder, D.M., . . . Fritsch, E. (2002). Topical corticosteroid therapy for acute radiation dermatitis: A prospective, randomized, double-blind study. British Journal of Dermatology, 146, 983–991.
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 took place at the University of Innsbruck in Austria.
The study used a prospective randomized double-blind study design with comparison to historical controls.
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.
Schmoll, H.J., Aapro, M.S., Poli-Bigelli, S., Kim, H.K., Park, K., Jordan, K., et al. (2006). Comparison of an aprepitant regimen with a multiple-day ondansetron regimen, both with dexamethasone, for antiemetic efficacy in high-dose cisplatin treatment. Annals of Oncology, 17(6), 1000-1006.
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
Patients were considered treatment failures if they needed to take rescue medication.
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.
Schmitz, K.H., Ahmed, R.L., Troxel, A., Cheville, A., Smith, R., Lewis-Grant, L., . . . Greene, Q.P. (2009). Weight lifting in women with breast-cancer-related lymphedema. New England Journal of Medicine, 361(7), 664–673.
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 took place at community fitness centers near participants' homes in Philadelphia, PA.
The study used a randomized controlled trial design.
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.
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.
Schmitz, K. H., Courneya, K. S., Matthews, C., Demark-Wahnefried, W., Galvão, D. A., Pinto, B. M., . . . American College of Sports Medicine. (2010). American College of Sports Medicine roundtable on exercise guidelines for cancer survivors. Medicine and Science in Sports and Exercise, 42, 1409–1426.
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:
Recommendations for exercise prescription were as follows:
General activity guidelines were as follows:
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.
Schmitz, K.H., Ahmed, R.L., Troxel, A.B., Cheville, A., Lewis-Grant, L., Smith, R., . . . Chittams, J. (2010). Weight lifting for women at risk for breast cancer-related lymphedema: A randomized trial. JAMA: The Journal of the American Medical Association, 304(24), 2699–2705.
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 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.
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.
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.
Schmitz, K. H., Holtzman, J., Courneya, K. S., Masse, L. C., Duval, S., & Kane, R. (2005). Controlled physical activity trials in cancer survivors: a systematic review and meta-analysis. Cancer Epidemiology, Biomarkers and Prevention, 14, 1588–1595.
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.
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.
Schmitt, T., Goldschmidt, H., Neben, K., Freiberger, A., Husing, J., Gronkowski, M., . . . Egerer, G. (2014). Aprepitant, granisetron, and dexamethasone for prevention of chemotherapy-induced nausea and vomiting after high-dose melphalan in autologous transplantation for multiple myeloma: Results of a randomized, placebo-controlled phase III trial. Journal of Clinical Oncology, 32, 3413–3420.
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.
Prospective, placebo-controlled, randomized, double-blinded, parallel-group, single-center study
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.
Schmidt, E., Thoennissen, N.H., Rudat, A., Bieker, R., Schliemann, C., Mesters, R.M., … Berdel, W.E. (2008). Use of palifermin for the prevention of high-dose methotrexate-induced oral mucositis. Annals of Oncology, 19, 1644–1649.
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.
Schmidt, T., Berner, J., Jonat, W., Weisser, B., Röcken, C., Van Mackelenbergh, M., & Mundhenke, C.W. (2017). Influence of arm crank ergometry on development of lymphoedema in breast cancer patients after axillary dissection: A randomized controlled trial. Journal of Rehabilitation Medicine (Stiftelsen Rehabiliteringsinformation), 49, 78–83.
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.
PHASE OF CARE: Late effects and survivorship
Randomized, controlled trial
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.
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.